Author: Benjamin Mitchell

Phase Genomics Announces Funding to Accelerate Discovery of New Lysin-Based Precision Antimicrobials

 

SEATTLE (March, 4, 2024) – Phase Genomics, Inc., a leading innovator at the forefront of genomics technology development, today announced $1.5MM in new funding from the Bill & Melinda Gates Foundation to fuel a new antimicrobial discovery platform. Leveraging the power of lysins, phage-derived proteins that selectively kill specific bacteria and archaea, the program aims to address two immediate threats that will shape the next century: a growing global antibiotic resistance crisis and the challenge of reducing global greenhouse gas emissions. The foundation of this effort rests on Phase Genomics’ proprietary global phage atlas, developed with support from the Gates Foundation. Under this project, Phase Genomics will deploy its platform to develop antimicrobial agents that bypass resistance against Campylobacter infections and methanogenic archaea in ruminants that drive global methane emissions.

“Our work at the frontier of microbiome research has unlocked a wealth of new insights on phages, the viruses that infect bacteria. Now, with support from the Gates Foundation, we’re harnessing our global phage database with the goal of improving human and environmental health and providing a critical alternative to traditional antibiotics,” said Ivan Liachko, PhD, founder and CEO of Phase Genomics. “The need for breakthrough therapeutics to combat the growing AMR crisis is urgent. We’ve built the right technology to identify and engineer lysin candidates primed to combat microbes both in environmental settings as well as emerging AMR biothreats and help overcome the industry-wide inertia facing novel antibiotic development.”

Derived from bacteriophage (or simply, phage) genomes, lysins are highly specific lytic proteins that kill bacteria by dismantling the cell wall structure, sparing off-target healthy microbes that are often collateral damage in traditional, systemic antibiotic treatment. Lysin-based antibiotics are well-suited for rapid, scalable biomanufacturing and deployment. Targeted bacteria are also much less likely to develop resistance to lysins than both traditional antibiotics and intact phages, providing a sustainable and durable framework to counter the accelerating antibiotic resistance threat. 

The new platform will build on data from Phase Genomics’ bacteriophage discovery engine which holds one of the world’s largest and most comprehensive collections of phage-microbe interactions containing hundreds of thousands of new host-resolved phage genomes. This continuously-growing phage interactome atlas is primed for the rapid discovery of wide-ranging classes of antimicrobial lysins derived from phages. The platform is superior to other approaches in both scale and accuracy, simultaneously resolving both microbial targets and the phages that infect them, with each pair containing a potential target-specific lysin candidate. Phase Genomics’ ProxiMeta™-powered phage atlas forms a deep well of target bacterial pathogens and new candidate biologics to tackle emerging drug-resistant pathogens and environmental biothreats.

This year-long project also marks a first-of-its-kind collaboration between Phase Genomics and Seattle-based Lumen Bioscience, who will assess lysin bioactivity in their robust and scalable microbial expression system.

Follow Phase Genomics on X and LinkedIn for the latest news and information.

 

About Phase Genomics 

Phase Genomics applies proprietary proximity ligation technology to enable chromosome-scale genome assembly, microbiome discovery, as well as analysis of genomic variation and genome architecture. In addition to a comprehensive portfolio of laboratory and computational services and products, including kits for plants, animals, microbes, and human samples, they also offer an industry-leading genome and metagenome assembly and analysis software.

Based in Seattle, WA, the company was founded in 2015 by a team of genome scientists, software engineers, and entrepreneurs. The company’s mission is to empower scientists with genomic tools that accelerate breakthrough discoveries.

 

Contact

Eric Schudiske

eric@s2spr.com

Bacterial pathogens have their own nemesis, and mimicking it can help solve the global AMR crisis

image of the globe surrounded by images of plants and viruses

 

Decades of antibiotic use – and abuse – are triggering a global rise in antibiotic resistance and limiting the usefulness of these life-saving drugs. In a nod to the adage, “The enemy of my enemy is my friend,” a solution may lie with bacteria’s oldest adversary: phages, the viruses that prey upon them. Our team at Phase Genomics is harnessing groundbreaking new metagenomic data and AI to tap into the evolutionary innovations of phages – and to eradicate dangerous microbial pathogens with surgical precision.

 

The need could not be greater. Fewer new antibiotics are hitting the market. The UN estimates that by 2050, worldwide deaths from antibiotic-resistant “superbugs” will overtake deaths from cancer.  Early 20th century scientists explored deploying phages to cure bacterial infections, an idea that has been recently resurrected. Phages are a staggeringly diverse class of bacteria-killers. By one estimate there are 1031 of them on this planet right now, vastly more than all living organisms combined. But using phages to cure infections has its own drawbacks: Mass production is difficult since phages only grow in bacteria, which can be difficult to culture, and it turns out bacteria have a barrage of defenses against intact viruses, imparting resistance against them.

 

While phages present one opportunity to help us stave off a return to the pre-penicillin past, we can also use their anti-bacterial weapons to launch a new arsenal rooted in synthetic biology. Phages produce proteins called lysins to destroy their hosts’ cell walls. These proteins have evolved over millennia to specifically target the phages’ hosts. They can be purified and used as precision antimicrobials, molecules that specifically kill the target bacteria without the collateral damage and resistance brought about by traditional wide-spectrum antibiotics.

 

Our team has used our unique genome sequencing technology to build the world’s largest catalog of the genomes of phages and the microbes that they attack – including the sequences of lysin proteins that they make. We’re harnessing this catalog to design, synthesize, and perfect lysin-based therapeutics that can attack bacterial pathogens safely, effectively, and with a surgical precision that today’s antibiotics lack.

 

Lysins hold tremendous advantages over traditional antibiotics. Antibiotics take out swathes of bacteria in our microbiomes that are essential for good health, leaving us more vulnerable to future infections – like the dreaded C. difficile – as well as to immune dysregulation. Yet most lysins target only the phage’s host species and its close relatives. And though antibiotic resistance spreads rapidly via plasmids, bacteria struggle to evolve resistance to exogenously introduced lysins.

 

Our collective knowledge of lysins to date comes largely from isolated experiments on phages or small-scale genomic studies. To deploy lysins as a life-saving solution, we need detailed knowledge of the intricate and intimate interactions between phages and bacteria. Phase Genomics has led this effort by building a vast catalog containing hundreds of thousands of phage genomes from different microbial environments. Our proprietary ProxiMeta technology employed for these experiments preserves unique information about essential ecological interactions in these microbiomes, including the host bacterial species that specific phages target. Thanks to this large and growing catalog of phage-microbe interactions, for many pathogenic bacteria, we can find specific lysins that could turn its cell walls into Swiss cheese.

 

We are using this foundational knowledge to build the first foundry for lysins. With support from the Bill and Melinda Gates Foundation, Phase Genomics is collaborating with Lumen Bioscience to design, grow, and purify lysins identified by our catalog. This proving ground will serve as the foundation for a future pipeline for lysin design – augmented by machine learning to hone target specificity, perfect performance and even create entirely new lysins with a desired target specificity. To make a custom-designed lysin against almost any bacteria, we would need to find a phage – and its lysin – that attacks it. This approach to lysin research and discovery has applications even beyond medicine, such as critically needed environmental remediation.

 

Our goal to develop therapeutic lysins would upend the existing paradigm for treating bacterial infections. Today, medical professionals have a shrinking pool of imperfect antibiotics that cut a swathe through our microbiomes to take out the bacterial bad guys. With lysins on the shelf as an option, we would be taking away this machete, and replacing it with a scalpel.

 

An Ancient Fungal Affair

two fungi exchange love letters in a whimsical forest scene

 

New genomic technology reveals the parental past of “ancient asexuals,” paving a route to crop engineering and soil remediation with symbiotic fungi

 

In a warming, crowded world, we need more help than ever from plants. But maximizing the bounty from crops — from food to fuel to fibers — means coaxing plants to draw minerals and nutrients from soil more effectively, and paying special heed to the tiny, often-overlooked fungi that make this possible.

Plant roots have symbiotic relationships with fungi that stretch back eons. For example, arbuscular mycorrhizal fungi, or AMF, have been cozying up to plant roots for at least 400 million years. In exchange for carbon-rich lipids from their hosts, AMF — named for the branch-like structures their bodies form within plant roots — help host defenses against pathogens, deliver water and increase absorption of nutrients rich in nitrogen, potassium and phosphorus. They also boost plant diversity.

Thanks to this ecological generosity, AMF are used as crop stimulants and in soil remediation. Their lipid lust also makes them good at carbon sequestration. Theoretically, engineered AMF strains could mount an even better performance in these essential tasks. But scientists have long viewed certain features of AMF, particularly their genetic structure and life cycle, as evolutionary puzzles that must be solved to make strain engineering possible and build better symbionts.

Working with Phase Genomics, scientists at the University of Ottawa recently overcame this barrier, successfully sequencing the genomes of four strains of the most widely studied AMF species, Rhizophagus irregularis. Using Phase’s proximity-ligation sequencing techology, they showed for the first time that the genomes of AMF are simultaneously more straightforward and more surprising than many mycologists had dared to dream.

Armed with this knowledge, scientists can plan new approaches to engineer AMF strains for applications in biomass production, soil remediation — and beyond.

 

The mysterious kary carryall

For years, the more scientists looked at AMF, the more questions they had. AMF bodies are essentially bags of haploid nuclei — tens of thousands, all sharing a common cytoplasm. And that’s not all.

“There were many, many outstanding questions about AMF,” said Dr. Nicolas Corradi, leader of the University of Ottawa team. “This was primarily because these fungi are always multinucleated and lack observable sex. It was suggested that AMF have an ‘oddball’ genetics and evolution.”

They were assumed to be “ancient asexuals,” who must’ve somehow thrived without the gene-shuffling benefits of sexual reproduction.

Dr. Corradi and his colleagues were determined to find out if that’s the case, and in the process began to shatter AMF’s asexual reputation. In 2016, they showed that Rhizophagus irregularis strains harbor evidence of sexual reproduction, including finding some of the genes needed for it. In some strains, all nuclei were genetically identical. But other, more robust and resilient AMF strains — termed heterokaryons — harbored two distinct populations of nuclei in their cytoplasm. More recently, Dr. Corradi and his team reported that the two populations of nuclei in heterokaryons change in abundance, depending on their host plant.

“But these were, however, based on fragmented genome datasets,” said Dr. Corradi.

To know for sure what was going on in AMF heterokaryons, the team needed a method to sequence the complete genomes of both populations of nuclei, allowing more complex studies of gene expression, genetic exchange and evolution in these puzzling fungal packages.

 

Would you prefer carrots or chicory?

Working with Phase Genomics, Dr. Corradi and his team employed a combination of proximity ligation (Hi-C) and PacBio HiFi data to sequence the genomes of both nuclear populations in four Rhizophagus AMF heterokaryon strains. Surprisingly, all four strains harbored genomes largely similar in structure — 32 chromosomes, with clear delineations between gene-rich and gene-poor regions — but highly divergent in sequence. For all four strains, the two populations of nuclei were essentially haplotypes, derived from parental strains during prior sexual reproduction.

Equipped with eight complete genomes — two haplotypes among four strains — the team followed-up with gene-expression analyses and discovered that each haplotype was transcriptionally active. But within an individual strain, haplotype gene expression patterns were not equal.

“AMF heterokaryons carry two haplotypes that physically separate among many thousands — potentially millions — of co-existing nuclei,” said Dr. Corradi. “This is unheard of in any other organism. But each ‘parental genome’ also regulates different biological functions, and these change depending on the plant host.”

They recorded at times dramatic shifts in haplotype abundance and expression depending on the AMF heterokaryon’s plant host — carrot versus chicory, for example. This suggests that each haplotype makes specific and unique contributions to the AMF heterokaryon’s phenotype. Future studies will have to tease out what role the plant host is playing, if any, in these shifting expression and abundance patterns.

 

Sex, but when? And more new mysteries

In assembling these long-sought genomes that co-exist within a common cytoplasm, Hi-C has revealed that Rhizophagus AMF heterokaryons are not as complex as once thought, or feared. Both haplotypes within each heterokaryon appear to arise through some past sexual reproduction event, contribute to the AMF’s phenotype and have unique gene expression patterns based on plant host. Their surprisingly ordinary genetic behavior — at least, ordinary for fungi — means it could be possible to engineer AMF that are even better symbionts for specific hosts, helping to boost crop biomass or improve resilience, for example. Engineered strains could also aid in soil remediation, or store carbon that would otherwise end up above ground or in the air.

The findings, coupled with the team’s previous experiments, also bring new mysteries into focus: AMF strains appear to employ a mixture of sexual and asexual reproduction, similar to other fungi. But scientists have never witnessed AMF sexual reproduction — a potentially useful tool for engineering strains. The new genome sequences will also serve as a point of comparison as scientists investigate whether the hundreds of other AMF species are similar to Rhizophagus — and their potential to transform agriculture.

A Year in Review: 2023

A year in review 2023 phase genomics

 

Another year has flown by with great accomplishments and advancements from researchers around the world wielding the latest in proximity ligation technology. As the year draws to a close, we at Phase Genomics would like to highlight some of the milestones that have been crossed in 2023 before setting our sights on an even more promising new year.

 

Advancing Global Health Research and Beyond

In 2022, supported by the Gates Foundation and NIAID, we set out to assemble a global-scale atlas of phage-bacteria interactions, discover looming antimicrobial resistance (AMR) biothreats, and identify potential phage-based solutions to public health crises. Throughout 2023, the rapidly-growing atlas is now the world’s largest and will form the backbone of an AI-powered global biodefense shield for AMR pandemic prevention and phage-based therapeutic discovery.

 

While our analytical platform has pushed these innovations further, our proximity ligation (Hi-C) technology has been aiding researchers and driving findings across a wide range of scientific endeavors. Click below to read some featured publications or check out the 200+ publications that have been published using Phase Genomics technology here

 

nature cancer publication

 

Metagenomics Innovation of the YearBiotech breakthrough award 2023

This year, we were thrilled to have been named Metagenomics Innovation Of The Year for 2023 by BioTech Breakthrough, a leading independent market intelligence organization. It is an honor to have been selected as the recipient of this award amongst more than 1,500 nominations from over 12 different countries and we are excited to support more discoveries in 2024.

 

Ukrainian Startup Day

Ukraine’s startup and innovation ecosystem is brimming with highly skilled talent, entrepreneurship ingenuity and immensely creative, motivated leaders. Another year into a war that continues to inflict tragedy and destruction across the country, the tremendous resolve, tenacity and pride that form a cornerstone of Ukraine’s culture of innovation is strong and enduring.

 

Last May, we  brought together startup founders and ecosystem builders to discuss how the war has impacted their work, their startups’ operations, and their forward-looking focus and priorities as leaders and founders, as well as how the global life sciences community can help in the months and years ahead. Watch the event recording here.

 

Company Highlights

We are proud of the growth our company has made over the past year. Within Phase Genomics, we have had team members travel around the world, seen new furry friends appear in Zoom meetings, and welcomed several babies to the expanding families on our team. 

 

In addition to the personal growth at Phase Genomics, there have been numerous professional highlights that appeared in news outlets throughout 2023. Check out some of the headlines below. 

 

Gates Foundation funds biotech company cataloging the viruses that infect bacteria (GeekWire)

Phase Genomics Collaborates with Element Biosciences to Optimize Cytogenomics for Liquid and Solid Tumor Samples (BusinessWire)

GeekWire Awards: How this Ukrainian-born CEO created a biotech startup ‘where curious scientists thrive’ (GeekWire)

Advanced Tools Transforming the Field of Cytogenomics (SeqAnswers)

40 Under 40: Kayla Young, Phase Genomics (Puget Sounds Business Journal)

 

A Look into 2024

In 2024, we are looking forward to taking our technology further to reach new heights and drive innovation across even more facets of science and medicine. Continuing with our growing phage-host interaction atlas, we are working towards finding solutions in combating antimicrobial resistance and pushing forward phage therapies. In the human genomics space, we are expanding our applications in cancer research, exploring opportunities in reproductive genetics, and advancing diagnostics. 

 

We hope you will follow us on our journey on X (formerly Twitter) and LinkedIn as we lead genomics innovation to an insightful and healthy future. 

 

Happy New Year from our team at Phase Genomics!

photo of phase genomics team

Phase Genomics Announces New Funding to Develop AI-Based Diagnostic Platform for Cancer

 

$2.5M in funding from the National Cancer Institute and Andy Hill CARE Fund will accelerate Phase Genomics’ proprietary OncoTerra™ platform toward clinical use, unlocking new genome-wide cytogenetic insights for acute myeloid leukemia and colorectal cancer

 

Monday, August 7, 2023

 

SEATTLE– Phase Genomics, Inc. a leading developer of cutting-edge genomic solutions, today announced $2.5M in non-dilutive funding to extend its AI-driven OncoTerra™ platform from the research setting toward clinical care for acute myeloid leukemia (AML) and colorectal cancer. The project is fueled by a $2M SBIR award from the National Cancer Institute and $500K from Washington State’s Andy Hill CARE Fund to establish a new clinical predictive paradigm based on the landscape of chromosomal aberrations in cancer to guide treatment decisions.

 

“We’re taking a pivotal leap toward integrating a new cytogenomic approach into clinical care to revolutionize treatment decision-making. The new funding will help us deliver a rapid assay that combines the collective power of today’s common cytogenetic solutions at a fraction of the cost and with added predictive power,” said Ivan Liachko, PhD, Phase Genomics founder and CEO. “Utilizing OncoTerra for patients with AML and colorectal cancer will reduce resource burdens for health systems, diagnostic laboratories and, most importantly, help the patients themselves.”

 

The proprietary proximity ligation sequencing-based platform, OncoTerra, is purpose-built to deliver more actionable insights for clinical decision making than karyotyping, fluorescence in situ hybridization (FISH), and chromosomal microarrays (CMA) as frontline cytogenetic diagnostics with a single assay. The platform unlocks genome-wide insights from a wide array of sample types, including blood, fresh, frozen, and formalin-fixed paraffin-embedded tissues, delivering the value of scalable cytogenomics for solid-tumor and blood cancers in the research setting.

 

Phase Genomics will leverage the two-year SBIR award to use OncoTerra to generate data from hundreds of archival samples. Data from the study will fuel Phase Genomics’ development of an AI-based model that delivers a predictive score, the Chromosomal Aberration in Oncology Score (ChAOS™), with the potential for patient risk assessment and to help guide future treatment decisions. Evidence from this observational study, which will include 500 AML patient samples, builds upon preliminary studies in hundreds of patient samples of diverse cancer types and will form the cornerstone of future clinical research to establish the utility of OncoTerra and ChAOS in clinical care.

 

An additional $500K award from the CARE Fund will be deployed to extend the ChAOS model to colorectal cancer with a specific focus on underserved populations in the Pacific Northwest. Although a variety of omics-based diagnostics are available, recent studies show that they are not equally accurate for all cancer patients owing to unaccounted-for genomic diversity in under-studied populations. The CARE Fund award will advance the development of ChAOS to address this disparity.

 

Follow Phase Genomics on Twitter and LinkedIn for the latest news and information.

 

ABOUT PHASE GENOMICS

Phase Genomics applies proprietary proximity ligation technology to enable chromosome-scale genome assembly, metagenomic deconvolution, as well as analysis of structural genomic variation and genome architecture. In addition to a comprehensive portfolio of laboratory and computational services and products, including Hi-C kits for plants, animals, microbes, and human samples, they also offer an industry-leading genome and metagenome assembly and analysis software.

 

Based in Seattle, WA, the company was founded in 2015 by a team of genome scientists, software engineers, and entrepreneurs. The company’s mission is to empower scientists with genomic tools that accelerate breakthrough discoveries.

 

ABOUT ANDY HILL CARE FUND

The Andy Hill Cancer Research Endowment (CARE) Fund invests in public and private entities to promote cancer research in Washington. Through research grants and strategic partnerships, the CARE Fund aims to improve health outcomes by advancing transformational research in the prevention and treatment of cancer. The Washington State Legislature created the CARE Fund in 2015 and this public investment in cancer research is maximized by private and nonstate matching funds.

Far and wide: New technology reveals the long arm of viruses in microbial ecosystems

Hydrothermal vent on ocean floor depicting the microbial environment of the featured study

Hydrothermal mat sampling aboard R/V Roger Revelle using ROV Jason. Credit: R/V Roger Revelle, Scripps institute of Oceanography.

 

For decades, biologists largely studied microbes and their viruses in isolation, nurtured in laboratory cultures. Yet, to paraphrase the poet John Donne, no microbe is an island. In recent years, scientists have recognized this by studying microbes not as individual species, but as part of the larger microbiome: the communal ecosystems, each home to many different types of bacteria and archaea, in which most microbes reside. It is in these realms that microbes display their collective might. From guts to geysers, tiny tales of competition and cooperation within microbiomes have big effects on our health and environment — such as the spread of antibiotic resistance and the stability of food webs.

 

Revealing microbiome mechanics

Traditional, laboratory-based methods struggle to probe the individual components of the microbiome. But “metagenomics” allows us to study the community at large. Metagenomics is the sequencing of DNA from microbial communities, and metagenome-assembled genomes — or MAGs — put together using ever-more sensitive tools and processes, are increasingly able to resolve the inner workings of these complex ecosystems.

Recently, a collaboration between Phase Genomics and a team at Harvard University on a metagenomics project showed that phages — viruses that infect bacteria and archaea — have a surprisingly broad impact on the microbiome of a seafloor hydrothermal vent. Using a technique called proximity ligation (Hi-C), which cross-links DNA strands from the same cell before DNA extraction and sequencing, researchers reconstructed MAGs in this community and found that diverse microbes, including bacteria and archaea separated by billions of years of evolution, sported records of past encounters with the same phages. One explanation is that the phages have an unheard-of level of host diversity — one certainly not predicted by laboratory experiments. Another is that these deep-sea microbes may somehow “share” adaptive immunity across broad and deep evolutionary gulfs.

If phages have similarly broad impacts far above the ocean floor, scientists may have to rethink how communication, cooperation and evolution shape microbiomes — and how they impact the larger creatures, like us, that depend on them.

 

Tapping the archive

Microbiomes teem with phages. But deciphering their reach is no easy task. Thankfully, some bacteria and archaea are hoarders. Their CRISPR-based immune responses record past phage infections by inserting short fragments of phage genomes into a specific region of their own genome. Some studies have even sought to reconstruct the reach of phages in a microbiome by probing the content of these areas — known as spacer regions. Yet, the approach has its drawbacks.

“Spacer regions are rich in repeats, so they don’t get sorted well in the MAG assembly process,” said Yunha Hwang, a doctoral student at Harvard University. “That creates a bias regarding which spacers and phage fragments are ultimately assembled into MAGs.”

Hwang has studied these genetic archives of microbial immunity, and previously reported that, in a desert microbiome, phages may have broad host ranges.

“It was a preliminary result, but very exciting,” said Hwang. “I wanted to see if this was a wider feature of microbiomes, and I wanted to avoid that assembly bias.”

 

Achieving Hi-C depth in deep oceans

Hwang and Peter Girguis, a professor at Harvard, worked with Phase Genomics to employ a metagenomic approach centered on Hi-C, which, by preserving physical linkages between DNA fragments present in the same cell, eases the process of resolving repeat-rich regions like CRISPR spacers.

Hwang collected samples from the microbiome near a hydrothermal vent in the Gulf of California’s Guyamas Basin. Microbial communities like this employ “alternative” metabolic pathways — relying on the plume’s rich geochemical outflow for nutrients, energy and raw materials instead of the sun-based food webs more familiar to surface-dwellers. As soon as she reached port in San Diego, Hwang shipped the microbiome samples to Phase Genomics for cross-linking, DNA extraction, sequencing and MAG assembly.

The spacer regions of the MAGs assembled via Hi-C showed similar profiles of past phage infection compared to conventional spacer-sequencing and assembly. But the higher-quality Hi-C MAGs also eased the search for phage fragments within CRISPR spacers. And, as in Hwang’s study of desert microbiomes, individual phages in the hydrothermal vent microbiome had a broad reach — including bacteria to archaea.

“This was so baffling to us, because these are two separate domains of life,” said Hwang. “The ability for a phage to infect a host depends on fundamental properties of cell biology, and bacteria and archaea are so different — their membranes, their proteins, their genomes. So, what does this mean?”

Another puzzle is that bacteria and archaea that are linked by symbiotic relationships — such as eating one another’s metabolic leftovers — were also more likely to harbor genomic fragments of the same phages in their CRISPR spacers.

 

Spread the word

One theory to explain these findings is that phages within microbiomes, which can be hard-pressed for space in these close-knit communities, have evolved to infect hosts with radically diverse membrane compositions, host defenses and cell biology. But that is not the only possibility. Another is that symbiotic partners, separated by billions of years of evolution but united at the dinner table, may be sharing more than just a meal.

“In symbiotic microbes, when one population or species gets infected by a phage, there could be a selective advantage in sharing that adaptive, genetically encoded immunity with your partners,” said Hwang.

Future metagenomic studies of other microbiomes may help resolve these theories, or sire new ones. But the eventual explanations will undoubtedly force scientists to rethink how genetic information flows within microbiomes.

“How do bacteria and archaea build up ‘resilience’ in such closely packed communities?” said Hwang. “Perhaps one way that happens through selective pressure to share records of past phage infections widely. Keeping your neighbor healthy keeps you healthy.”

 

Sounds familiar

Once upon a time, far above the ocean floor, children played a game called “telephone”: passing a phrase from one person to another — in the form of a whisper — to see how the message changed as it is heard by each ear and transmitted by each voice.

It seems that bacteria, archaea and phages play similar games, which is just the latest surprise that metagenomics has revealed about microbiomes. It will certainly not be the last.

Pass it on.

 

 

A Year in Review: 2022

Text on orange and blue background reads: Phase Genomics, A Year in Review 2022

 

With 2023 well under way, here is a quick glimpse into the rearview mirror of Phase Genomics in 2022.

 

Last year was an exciting one for those of us in the genomics space. Exploring genomic interactions and refining methods to assemble the most complete genomes, the biotech sphere reached new heights and researchers uncovered new discoveries of our biological world. The use of AI boomed this year as developers set out to unravel complex problems in both everyday life and life sciences. Wielding these tools, we made significant progress in understanding plant and animal genomes, viromes, interactomes, and their relation to health and disease. 

 

These advancements have the potential to revolutionize the way we approach a wide range of medical conditions spanning viral infections, antimicrobial resistance, and cancer. As we move into the new year, we can look forward to even more exciting advances in genomics that will help us to close gaps in understanding and facilitate discoveries. Here’s a look at some proud moments from 2022.

 

Research Spotlights

Last year, we surpassed 150 papers published using our genome assembly technology. There’s a lot to share: advances have been made in a broad range of fields, from microbiology to oncology research, thanks to the researchers leveraging our technology. We appreciate their work and are thrilled to see their projects succeed! Here are some highlights from this year:

 

Published in Nature Biotechnology, breakthrough metagenomic research, featuring ProxiMeta Hi-C data, assembled over 400 high-quality MAGs and hundreds of host-viral/plasmid associations from a single fecal sample.

 

Genomic sequencing techniques unearthed surprises about life and evolution. This article features new studies that  illuminate a rarely-seen evolutionary transition in sex chromosomes. 

 

A study using ProxiMeta linked AMR genes to their genomic, plasmid, or viral host in microbiome samples. Their data was used to track horizontal gene transfer of antimicrobial resistance to Salmonella in chickens.

 

With so many projects being published in 2022, we couldn’t possibly capture everything in one blog, see all the new discoveries involving Phase Genomics here.

 

Company Highlights

From new products to new grants, 2022 was a big year for our team. Here’s a look at 2022’s news-worthy moments:

 

In the News

Podcasts

Genome Startup Day

Supporting Ukraine

  • We support humanitarian efforts in Ukraine because it is right and because it is personal – several team members have family residing in the country. Phase Genomics, along with many others in the biotech field, began sending aid to those suffering in this tragedy abroad. More here.
  • Charities we support: Razom for Ukraine, Voices of Children, UN Humanitarian Crisis Fund

 

Looking Forward to 2023

Thank you to everyone on our team, the amazing scientists using our tools, and our supporters for making these achievements possible. With 2023 already rolling in, we are hitting the ground running. Keep in touch with us on our social media accounts (Twitter, LinkedIn, YouTube) to stay updated on our new endeavors, recent research, and more news from our company.


Happy New Year from the Phase Genomics Team!

Photograph of Phase Genomics team outside

Bacteria Breakthroughs: Insiders’ Reflections on Commercializing Discoveries in the Phage Industry

 

During this Fall’s Genome Startup Day event, we welcomed researchers and entrepreneurs that have taken the plunge into commercializing their phage discoveries. John Eisen, PhD, UC Davis professor and renowned genomics and microbiology researcher, spoke with Ivan Liachko, PhD, Founder and CEO for Phase Genomics, for a candid and lively fireside chat on the current state of phage research and innovation followed by a panel discussion with startup founders Jessica Sacher, PhD, of Phage Directory, Nathan Brown, PhD, of Parallel Health and Minmin (Mimi) Yen, PhD, of PhagePro.

 

 

In the opening moments of the Fireside Chat, Dr. Eisen regaled us with the origin of his fascination with microbes. Converting from an East Asian Studies major to a Biology major at Harvard College, Dr. Eisen was initially interested in birds, butterflies, and plants. However, an opportunity at a faculty member’s lab shifted his focus to the microbiome. Eisen began researching the bacteria residing in tubeworms, an ocean-dwelling species with no mouth or digestive system.

 

“It was just so weird, so unusual. Ever since then, I’ve been working on microbes”

 

This experience launched Eisen’s career into the strange and mysterious world of microbes. His research has since expanded to include microscopic creatures from the space station, depths of the ocean, Antarctica, and more recently, cat butts. While a seemingly peculiar topic of research, performing sequencing on felines is not a rare occurrence in the genomics community. Host, Dr. Ivan Liachko, notes projects such as Kitty Biome and Phase Genomics’ own Meowcrobiome, which also caught traction in earlier years. 

 

Looking forward, our fireside chat speakers revealed their expectations for the rapidly-blooming phage industry. “People are finally getting a handle on the functional contributions of some of these microbes,” Eisen shared. Thus, doors are being opened to (legitimately) commercializing their unique properties. “I’m not sure the overselling is going down, but the legit stuff is going up,” Eisen concluded (referring to his Overselling the Microbiome Award, which brings to light companies that were over-ambitious in bringing microbiome products to the market).

 

Finishing their discussion, Liachko and Eisen focused on the role of startups in the phage industry. Eisen advocates for the flexibility of academic and industry careers, not seeing their differences as a barrier, but as a landscape in which one can pursue numerous options by following their own creativity and curiosity. Liachko voiced several anxieties early founders, specifically those leaving student and postdoc positions, may have when making the jump to industry. The fear of entering the unknown, the struggle to find mentors, and how to set oneself up for success in the biotech industry–all with which our panelists had ample experience and advice to give.

 

Opening the panel, moderator Juliana LeMieux asked the startup founders how they were able to take a scientific discovery and transition it into a business model. With a range of phage-related companies represented at the (virtual) table, the panelists described their challenges, surprises, and successes in entering the business realm. 

 

Three Considerations for Early Founders

Here are the top three take-aways for early founders from this event’s panel discussion:

 

1. “Don’t be afraid to try and don’t be afraid of the rejection” -Dr. Minmin Yen

Dr. Yen, driven by her enthusiasm for phage research, started PhagePro, an early-stage biotechnology therapeutics company offering bacteriophage-based products to target bacteria and prevent infections in vulnerable communities. She discussed challenges she faced in convincing regulatory agencies and stakeholders to contribute resources to the project. To prepare for these conversations, Dr. Yen suggests getting out into the world and presenting your ideas to others in the entrepreneurial space. Get accustomed to being challenged and practice building your arguments. 

 

2. “Get a cofounder” -Dr. Nathan Brown

Dr. Brown, co-founder of Parallel Health, started his company to bring personalized cosmetics to the market through phages. When asked, “What’s the best thing about starting a company,” he was quick to reply “Working with my awesome co-founder.” Building strong working relationships are critical for all, but finding your co-founding complement is one of the strongest steps forward in beginning a company. A co-founder will not only aid in divvying up the commercial tasks, but also share the mental and emotional stresses of opening a business. 

 

3. “You need one friend who knows about startups” -Dr. Jessica Sacher

Dr. Sacher’s company, Phage Directory, was created as a “match-making” service connecting doctors and researchers with phages. The company’s mission is to facilitate access to phages for use in phage therapy and biocontrol. Throughout the panel discussion, the panelists discussed ways that they built a community around their innovations. From local entrepreneur meetups to chats with business-oriented peers and professors, our panel recommends early starters seek out advice and support from people that can connect to the entrepreneurial odyssey. 

 

Follow Genome Startup Day on Twitter and LinkedIn for more insights on biotech startups and to be alerted of future events.

Catching Evolution in the Act

Scientist studying chromosomes

 

Genome sequencing has confirmed some long-held theories about the blueprints of life. But it has also unearthed quite a few surprises. Scientists once hypothesized that the human genome consisted of upward of 100,000 genes. The decades-long Human Genome Project — as well as many next-generation sequencing studies — have prompted the downward revision of that figure to a relatively spartan 20,000 genes, more or less.

 

Evolution in action

 

If there is a lesson in this vast overestimation to our gene load, it is perhaps that evolution shapes genomes in unexpected ways.

 

The advent of more nimble and lithe methods for genome assembly and analysis holds the promise to unearth the surprises that evolution has wrought. These relatively new advancements include tools like Phase Genomics’ ultra-long-range sequencing, which reconstructs the sequence of chromosomes by using positional relationships between DNA sequences in the genome. These methods have grown sufficiently sophisticated to catch the quick transitions that transform populations and species.

 

Recently a team led by Dr. Leonid Kruglyak at UCLA employed these tools to catch evolution at work. Their discovery relates to sex determination, a complex developmental process that, in animals, generally kicks off when an immature gonad develops into either testes or ovaries. In humans and many animals, sex determination is governed largely by genes, and in turn shapes their genomes and evolutionary trajectories like few other biological processes can.

 

That special pair

 

For species with full genetic control over sex determination, the process often leaves its imprint on the genome in the form of sex chromosomes. In most animals, genomes consist of pairs of chromosomes called autosomes. But in addition to those autosomes, many animals — including us — harbor another set of chromosomes called the sex chromosomes. Sex chromosomes govern — or at least try to govern — whether the gonads develop into ovaries or testes, which  in turn influences the development of genitals and secondary sex characteristics.

 

Scientists have long theorized that sex chromosomes evolve from autosomes. Studies of young, relatively new sex chromosome systems, like those in the medaka, indicate that the transition happens fast. Yet the steps that transform a pair of autosomes into sex chromosomes are at best murky, with many questions unresolved. Much could be answered by catching this transition from autosome to sex chromosome in the act.

 

Behind the curtain

In a paper published June 1 in Nature, Dr. Kruglyak and his colleagues announced that they have found just such a transition: an animal with a pair of autosomes that is beginning to act like sex chromosomes. The researchers utilized Phase Genomics’ Proximo™ genome scaffolding platform and PacBio long reads to sequence and assemble a highly complete genome for a microscopic, freshwater flatworm, Schmidtea mediterranea. In many parts of its natural habitat across the Mediterranean basin, S. mediterranea reproduces by budding, without the need for sex. But some populations in Corsica and Sardinia produce the next generation through sexual reproduction.

 

The team, including lead and co-corresponding author Dr. Longhua Guo at UCLA, discovered that in these sexual strains of S. mediterranea, one pair of autosomes shows evidence of almost no genetic exchange, also known as recombination, during reproduction. This is a telltale signature of sex chromosomes. In addition, they saw that the unusual pair of autosomes harbors a large contingent of genes that play a role in developing sex-specific characteristics. Taken together, these genomic data finger these autosomes as a “sex-primed” pair that are in the process of evolving into fully fledged sex chromosomes.

 

Photo finishes

 

Future studies of S. mediterranea’s nascent sex chromosomes will likely fuel fresh inquiry and debate about this rarely-seen evolutionary transition. The answers will stretch far beyond flatworms. Studies of other recently evolved systems, such as in stickleback fish, show that sex chromosomes can play a decisive role in other poorly understood evolutionary transitions, such as the rise of a new species.

 

Beyond sex chromosomes, this study demonstrates the raw interrogative power of modern genome assembly and analysis methods. They can capture transitions — even the most brief and ephemeral. Applied appropriately, methods like these can help scientists make sense of a myriad of messy, complex processes that evolution shapes. These include some issues that hit as close to home as gonads, from curbing the spread of antibiotic resistance to protecting pollinators from annihilation. Evolution moves quickly. Now, so can we.

 

Funding the Future of Cancer Research

Genome Startup Day Spring 2022

Stories from Startup Founders and an Insider’s Advice on SBIR Grants 

 

Some of tomorrow’s biggest breakthroughs in cancer treatment are in the works today in startup labs across the US. On March 30th, we brought together CEOs and leaders in the cancer startup industry for a behind-the-scenes look at how emerging technologies are taking aim at one of the deadliest diseases in our world, and how these startup leaders are carving successful careers in the cancer tech landscape. Watch the replay of the event to hear their advice on deciding when to commercialize, how to scale up, and who to hire. 

 

 

Getting Started with SBIR

One of the struggles of starting a new company is the constant pressure to find funding. However, there are many options for various stage startup companies that are outside of Venture Capital. While VC funds are a great way to raise money to embark on your journey to commercialization, programs such as the Small Business Innovation Research (SBIR) Fund offer resources that allow founders to obtain funding without losing equity. The SBIR program’s goal is to create jobs in the U.S. by supporting commercially-directed, for-profit, small businesses. Submitting an SBIR proposal may be a daunting process, but during our fireside chat, Greg Evans – Program Director at the National Cancer Institute, SBIR – shared some helpful tips for those looking to take advantage of this resource. 

 

Common Mistakes

1. Not talking to the program officers in advance 

Evans emphasized, “Part of our job is to serve [as] a “help desk” function” – to be available to help people strategize on grant submissions and how to be competitive.” Program officers can help you construct the proper proposal, advise you on how much money to apply for, and direct you towards the right grants to pursue. Get in contact with them to plan out your proposal before submitting.

 

2. Applying for multiple grants

While your instincts may lead you to hedge your bets and apply for grants across several topics, Evans notes that the best proposals are the ones that have identified the scope of their project, and have committed to a market sector. Instead of sending in three proposals, pick your best proposal based on the data you have, competition in the market, strengths of people in your company, and make the business decision to focus your efforts.

 

3. Only applying for “priority areas”

The NIH does list Research Topics of Interest; however, this does not discourage companies from applying for grants outside of these topics. Evans notes that the burden is on the small business to have a product that is better than current competing products, regardless of if it is in a NCI “priority area.”

 

For more helpful tips on applying for an SBIR grant, including which letters of support you will need, watch the full Fireside Chat with Ivan Liachko and Greg Evans.

___________

Follow the Genome Startup Day Twitter and LinkedIn to get more startup information and to be invited to future events. Visit the Genome Startup Day website to see previous events.

Women’s History Month 2022

Women's History Month. Image of five women.

 

Happy Women’s History Month! Being in the biotech industry and working with a strong, diverse team of scientists, we want to take a moment to reflect on the history of women in science and how we can make a brighter history for future generations. This past month, we shared stories from women at Phase Genomics to celebrate their accomplishments and highlight their inspirations.

Below is a compilation of their video submissions as well as written submissions from Lauren Burgess, Research Associate; Emily Reister, Research Scientist; Hayley Mangelson, Lead Bioinformatics Scientist; Kayla Young, COO; and Mary Wood, Data Scientist.

 

Who is your favorite female scientist?

Elizabeth Blackwell

Elizabeth Blackwell

Lauren: My favorite female in STEM is Elizabeth Blackwell. Blackwell faced discrimination and obstacles in college when professors forced her to sit separately at lectures and often excluded her from labs. Despite these hardships, Blackwell was the first woman to graduate from medical school in the United States and became a strong activist for women’s health and education.

Emily: My favorite female scientists are the ones that I get to work with and have gotten to work with every day. My mentors in grad school served not only as scientific mentors, but coworkers and taught me not only be a good scientist, but to be a good mentor to others. I wouldn’t have graduated without them. I learned so much about being a good RNA biochemist as well as a good lab mate from them.

Temple Grandin

Temple Grandin

Hayley: My favorite female scientist would have to be Temple Grandin. She stands out in my mind because she was possibly the first female scientist that I heard a lot of talk about when I was growing up as a young person interested in science and biology. Her science is revolutionary, and I think she’s a fantastic mentor for women and neurodiverse people who are interested in STEM fields.

Mary: My favorite female scientist is Ada Lovelace. She was completely ahead of her time as woman in science in the 1800s and is considered by many to be the first computer programmer for her work on an algorithm designed to compute Bernoulli numbers.

 

Dian Fossey

Dian Fossey

Kayla: My favorite female scientist is Dr. Dian Fossey, a zoologist who died researching endangered gorillas in Rwanda in the eighties. She is critical to our understanding and knowledge of gorillas, their behaviors, and conservation efforts of the species. Dr. Fossey was brave, dedicated, and had a deep passion for animals that resonates with me, both as a child and as an adult.

What advice do you have for women in STEM?

Lauren: From Blackwell and my own experience as a recent first-generation college graduate, I learned that success is not measured by raw intelligence, but by persistence. My advice to women entering STEM is even when course loads to become seemingly impossible to manage, remember that it is possible with hard work. You are not alone in your struggle, and you will become stronger woman through overcoming these challenges.

Emily: Something that I’ve learned and I’m continuing to learn is to not be afraid to vouch for yourself, but especially don’t be afraid to vouch for those around you. To me, what makes a good scientist is one who not only understands every detail and minutia of what they’re working on but truly understands the impact of their work and the working environment that they foster. A good scientist is a good person and a good person to work with. Recognizing that as early as you can is really important.

Hayley: If you are a woman considering a STEM field, then I encourage you to challenge your own assumptions about what it means to be a woman. We deserve to feel confident and competent in our roles so that we can demand the equality and respect that we deserve.

Kayla: My advice I would give women (or anyone for that matter) that’s entering the STEM field is to find the people and the jobs you want and go and talk to them. Find that research scientist, or the project manager, or the director of R&D, or the business development human and take them to coffee and learn about their jobs. Ask them about the things that matter to you. If you don’t like the answers, then don’t settle for that company. The STEM field has so many opportunities, just go out and find what they are. For instance, I am a molecular biologist who doesn’t touch pipettes or sit at a bench – the opportunities are endless. More often than not, people are really willing to talk to you about their jobs and you just need to ask.

Mary: My best advice for women in STEM would be not to fear speaking your mind. As women, we’re often made to feel that we should make ourselves smaller in the world, and that can translate into not sharing good ideas or stating our preferences about our work. It’s ongoing work to overcome the societal messaging that encourages us to hold back, but it’s so important that we fight those instincts – we have important things to share!

What fascinates you about STEM fields?

Lauren: What I find the most fascinating about STEM careers is the versatility among occupations, yet we all share a common goal. When it comes to research scientists, STEM educators, and the many other STEM careers available, each occupation works to push our understanding of the universe and to build a brighter, more knowledgeable future. The STEM community is a powerful one and one I’m proud to be a part of.

Emily: I think what really fascinates me is the sub communities it fosters. STEM fields harbor and bring together really passionate people. What’s more fun than working with passionate people?

Hayley: My favorite part of being in a STEM field is that there are still so many unanswered questions and I feel I can make a real impact. I really do feel that the contributions that I’ve made so far are valuable and lasting contributions.

Kayla: I think what intrigues me most about the STEM fields is that they are ever-changing and very collaborative. This is a group of individuals that is, broadly speaking, working to contribute and improve the human experience, and that’s a very cool collaboration to be a part of. It’s a global community that’s working to solve big problems and ask fascinating questions, and it’s a community that I’m proud to both work in and be a part of.

Mary: It’s amazing to work on things that can make a difference in the lives of other people – from technological advancements that make the day-to-day more convenient, to breakthroughs in healthcare that save lives, science is transformational! Working in science helps hone your critical thinking skills! Not only does that make you a better scientist, but it’s so helpful in wading through the endless information now available to us in everyday life. Interacting with other scientists is the best! I’ve made so many great friends throughout my science education and career, and get to work with awesome, intelligent people.

Better together: long-range and long-read DNA sequencing methods close age-old blindspots in microbiome research

 

Since its debut, next-generation sequencing has not rested on its laurels. Improved sequencing platforms have reduced error and lengthened reads into the tens of thousands of bases. The debut of ultra-long-range sequencing methods that are based on proximity ligation (aka Hi-C) has brought a new order-of-magnitude into reach by linking DNA strands with their neighbors before sequencing.

Rapid progress in this field has birthed genome-resolved metagenomics, the sequencing and assembly of genomes from environmental samples to study ecosystem dynamics. But metagenomic experiments often undersample microbial diversity, missing rare residents, overlooking closely related organisms (like bacterial strains), losing rich genetic data (like viruses and metabolite gene clusters), and ignoring host-viral or host-plasmid interactions.

 

A revolution within a revolution

New sequencing platforms and methods can reform metagenomics from within. Phase Genomics has been a leader in genome-resolved metagenomics with its ProxiMeta™ platform, which leverages a method that physically connects DNA molecules inside cells before sequencing to generate highly complete genomes for novel bacteria and viruses. Boosting proximity-fueled methods with long-read platforms, such as the PacBio® Sequel® IIe system that can yield HiFi reads of up to 15,000 base pairs with error rates below 1%, could stretch its potential even further.

In a study published in Nature Biotechnology, a team — led by Dr. Timothy Smith and Dr. Derek Bickhart at the U.S. Department of Agriculture and Dr. Pavel Pevzner at the University of California, San Diego — employed both PacBio HiFi sequencing and ProxiMeta in a deep sequencing experiment to uncover record levels of microbial diversity from a fecal sample of a Katahdin lamb. Combined, PacBio HiFi sequencing and ProxiMeta eased assembly, recovered rare microbes, resolved hundreds of strains and their haplotypes, and revealed hundreds of novel plasmid and viral interactions.

 

Deeper diversity

The team constructed SMRTbell® libraries to generate HiFi data, and ProxiMeta™ libraries to generate long-range sequencing data. The two datasets allowed them to assemble contigs and create draft genomes without manual curation.

Researchers compared the breadth and depth of HiFi data-derived metagenome-assembled genomes, or MAGs, to control MAGs from assemblies of the same sample made using long, more error-prone reads. HiFi data yielded 428 complete MAGs from bacteria and archaea — a record number from a single sample. HiFi data also generated more low-prevalence MAGs, capturing a larger slice of the community’s diversity by picking up more genomes from less common residents.

 

The hidden actors

But no assembly method could be considered “complete” if it overlooked viruses, the most numerous members of virtually all ecological niches on Earth. These tiny players shape microbial communities in ways scientists are still trying to understand. For example, as agents of horizontal gene transfer, they help spread antibiotic resistance genes. And conversely, they have recently grown in popularity as a means to kill resistant bacteria in our ever-waging war against antibiotic resistance.

Phase Genomics’ ProxiPhage™ tool can already assemble high-fidelity viral genomes from microbial communities, even using only short-read sequencing data. But the new study shows that having HiFi helps considerably. The team identified 424 unique viral-host interactions, including 60 between viruses and archaea, which is a more than 7-fold increase over control samples. In total, the HiFi library included nearly 400 viral contigs, more than half of which came from a single family that infects bacteria and archaea. The ability to connect viruses with their microbial hosts in vivo is a unique property of Phase Genomics’ technology.

 

HiFi family trees

The long-range ProxiMeta libraries contained information that yielded more than 1,400 complete and 350 partial sets of gene clusters from archaea and bacteria for synthesizing metabolites such as proteasome inhibitors — the most uncovered to date. These clusters likely help some of these microbes colonize the gut. HiFi data picked up about 40% more clusters than control MAGs, illustrating just how much data is lost when long reads aren’t also highly accurate reads.

The team also used the HiFi-based MAGs to trace lineages within the community. They computationally resolved 220 MAGs into strain haplotypes, based largely on variations within single-copy genes. One MAG had 25 different haplotypes, which are likely strains of the same genus or species.

ProxiMeta ultra-long-range sequencing also linked nearly 300 HiFi-assembled plasmids to specific MAGs — revealing the species that hosted them in vivo. One plasmid, for example, was found in bacteria from 13 different genera. Long-range data also identified the first plasmids associated with three archaea, including Methanobrevibacter and Methanosphaera.

 

What’s around the bend?

This study has lessons beyond one lamb’s gastrointestinal tract. It shows decisively that the discovery power innate to long-range sequencing methods like ProxiMeta are greatly enhanced when wedded to high-accuracy sequencing methods like HiFi. Together, the two generate increasingly sophisticated metagenome assemblies for biologists to interrogate.

Applied to other environmental samples, this platform could illuminate the diversity and complexity of other microbial communities — from the bottom of the sea to mountain peaks, and within the body of every human being. It could probe pressing issues of our day, such as disease, soil health, and antibiotic resistance, a scourge whose spread and potential solutions — such as phage therapy — can only be forged through a thorough understanding of microbial diversity, interactions, and ecology.

A Year in Review: 2021

 

A look back at the year 2021.

The 21st year of the 21st century (a golden year, perhaps?) has come to an end. Looking back on the year that was abundant in vaccinations, canceled vacations, and virtual conferences, we would like to highlight the achievements that were made despite continuing challenges that face our communities. Amongst a rapid growth in company size, Phase Genomics has celebrated some big wins in 2021. This year’s successes include the launch of three new products, reaching over 100 scientific papers published, and aiding numerous record-breaking discoveries in the genomics space. We want to thank our clients for their support, our incredible employees for their hard work, and the adaptability of leadership to continue the company’s growth during unpredictable times.

 

Here’s a quick look at our highlights from 2021:

 

New Products

Grants

Publications

 

In the News

 

Webinars

Genome Startup Day

 

See You (Fingers Crossed) in 2022!

In 2022, we are hopeful that we will be able to return to conferences and see our friends, clients, and colleagues in person. We plan to expand our product line in the cytogenomics space, grow our team, and continue to serve all our clients with cutting-edge tools, including some upcoming surprises. Follow Phase Genomics and the latest developments in our ecosystem in real-time on Twitter and LinkedIn or by subscribing to our quarterly newsletter – PhaseBook.

We hope you had a safe, healthy, and relaxing Holiday Season and we look forward to seeing you in the New Year!

 

Phase Genomics staff aboard a pirate ship

Image from August 2021 work event with the Phase Genomics team aboard Queen Anne’s Revenge.

Ultra-long-range sequencing technology expands research opportunities in reproductive genetics and oncology

 

Phase Genomics’ recent release of the RUO cytogenomics platform, CytoTerra™, was accompanied by a webinar which covered an in-depth analysis of current technologies and emerging opportunities in reproductive genetics and oncology.

 

 

“The genome is the blueprint of life,” beginning the webinar, Ivan Liachko describes Phase Genomics’ history of discoveries and contributions to genomic research. Through the development of various genomic, metagenomic, and epigenomic platforms, Phase Genomics has risen as a leader in next generation sequencing (NGS) solutions. Now, the company’s latest platform leverages their ultra-long-range sequencing technology to be used for cytogenomic applications

 

Chromosome rearrangement is a known driver of many diseases, including cancer, infertility, developmental delay, and immunologic complications. Thus, the detection and treatment of these rearrangements is essential in the advancement of modern medicine and therapeutics. However, current methods are limited in scale, throughput, and resolution. Additionally, challenges in sample types and analysis constraints present a cascade of costly tests to run in order to assemble a complete view of the genome. Some of these challenges include culturing dividing cells for cytogenomics, obtaining advanced knowledge of the targeted abnormality for fluorescence in situ hybridization, and working within the limited scope of rearrangements detectable by chromosomal microarray analysis. Further complicating the process of genetic analysis, most cancer biopsies are stored as formalin-fixed paraffin-embedded (FFPE) samples—a wax-like encasing which kills the cells and traps the DNA. Historically, there has been no way to access the DNA to perform NGS testing in these sample types. However, recent cytogenomics platforms created by Phase Genomics do not require a priori knowledge, improve chromosomal abnormality detection, and unlock information in FFPE samples, offering a promising solution to many challenges in the oncology and reproductive genomics spaces. 

 

Phase Genomics’ new cytogenomics platforms, CytoTerra and OncoTerra, are powered by ultra-long-range sequencing—using proximity ligation data and artificial intelligence  to analyze the breadth of chromosome arrangements in a single assay—which eliminates the need for sequential testing, includes a scalable approach to genomic detection, and unlocks information stored in difficult sample types, including FFPE and frozen samples. 

 

Watch the webinar for more information on the expanding possibilities of chromosomal aberration detection and contact Phase Genomics to start a project.



Transcription

 

00:00:01:18 – 00:00:15:08

Speaker 1

Hi, everyone. My name is Ivan Liachko and I’m one of the founders and chief scientist at Phase Genomics. I’m joined today by Jill Tapper, our cytogenetics product manager. Today, we’re going to tell you about our new next generation cytogenomics platform.

 

00:00:15:19 – 00:00:36:23

Speaker 1

This new platform is powered by a unique next generation sequencing technology and has the power to transform how clinicians and researchers approach oncology and reproductive genetics. All right. Let’s get started. So, for those of you who are not familiar with Phase Genomics and what we do, essentially our thing is building genomes.

 

00:00:37:09 – 00:00:54:16

Speaker 1

What we do is we capture unique genomic information to reconstruct genomes and genome structure in order to transform research and clinical applications. We got our start by building cutting edge genomic tools to assemble genomes for non-model organisms.

 

00:00:55:00 – 00:01:13:09

Speaker 1

So, we came out a few years ago with the first chromosome scale non model genome scaffolds as a way of basically putting together an end-to-end chromosome scale genome for anything—for plants, animals, fungi. We’ve also developed tools to haplotype phase a genome of any size.

 

00:01:14:13 – 00:01:37:00

Speaker 1

This is something that at this point is fairly well accepted by the field. We’ve published this over 100 times. It’s even made it into the popular press. And what this sort of technology is based on is a method that has many names, the most descriptive of these is ultra-long-range sequencing.

 

00:01:37:10 – 00:01:52:11

Speaker 1

What it does is it allows us to sequence DNA molecules that are really far, far away from each other. And the way it works is you will take a cell that is intact and within the cell. The genome is condensed into this three-dimensional structure, right?

 

00:01:52:11 – 00:02:11:01

Speaker 1

Remember, a genome is just linear molecules being squished into a ball and they condense into these three-dimensional shapes. The way the technology works is it captures physical junctions between DNA molecules that are close to each other in three-dimensional proximity.

 

00:02:11:02 – 00:02:26:22

Speaker 1

So, in three-dimensional proximity with each other, we can capture these junctions and sequence them. And what that does is it tells us it gives us a way to count how often every part of the genome is close to every other part of the genome.

 

00:02:27:10 – 00:02:47:10

Speaker 1

And so, if you know how often two sequences are physically touching each other, you can figure out how close they are because the sequences that are closer touch more and sequences that are further touch less. And if you know this, if you know this sort of three-dimensional distance between all the sequences in the genome, you can

 

00:02:47:10 – 00:03:08:09

Speaker 1

reconstruct that into a genetic map, right? Sequences that are closer touch more sequences that are further touch less, and that enables you to do to basically use computational tools to reconstruct that information into a karyotype. And so, if you have a genome that you don’t know how it’s supposed to go together, you can use

 

00:03:08:09 – 00:03:23:05

Speaker 1

this information to scaffold it by arranging all the pieces. But if you have a genome like the human genome where you know what it’s supposed to look like, this is a really robust way of detecting rearrangements big chromosome scale karyotype, style rearrangements.

 

00:03:24:18 – 00:03:41:10

Speaker 1

There’s a lot of other things you can do with this technology. I’ll mention them briefly, just for reference. So, the first thing that I’ve mentioned is it allows us if you have this data, you can reconstruct essentially high-resolution genetic map for whichever organism it is you’re working with.

 

00:03:42:07 – 00:03:52:14

Speaker 1

But it also allows us to assemble and phase genomes de novo. So, when you don’t have a sort of a scaffold, a genome with some new organism you’ve never seen before, it allows us to assemble the genome from scratch.

 

00:03:53:10 – 00:04:10:22

Speaker 1

This technology allows us to understand the three-dimensional architecture of the genome. So basically, it allows us to study the 3D structure of a genome, which is a very, sort of very interesting biological property that every genome sort of lives in.

 

00:04:11:13 – 00:04:25:16

Speaker 1

We also have a number of cool tools in the microbiome space. So, this technology I won’t go into this technology has lots of really neat properties that allow us to discover new bacteria, new viruses, new mobile elements.

 

00:04:26:02 – 00:04:44:04

Speaker 1

It allows us to track the movements of mobile elements such as antibiotic resistance genes in infectious disease microbial environments, in addition to building a suite of wet lab molecular tools, which we, we sell all sorts of kits and services in the space.

 

00:04:44:16 – 00:04:58:23

Speaker 1

We also are a very informatically focused company. And so, we develop the tools that are needed to take this unique information type and actually turn it into actionable insights. So, we’ve developed everything so Proximo, our genome scaffolding platform.

 

00:04:59:04 – 00:05:10:12

Speaker 1

We’ve developed tools such as Falcon Phase, which allow us to phase genomes, haplotype-phase genomes. We have a number of tools for doing karyotype instead of genetic type studies, and that’s what we’re going to talk about today.

 

00:05:10:24 – 00:05:31:23

Speaker 1

And then we have a suite of methods that leverages this technology for microbiome discovery. ProxiMeta is for discovering new bacterial genomes, ProxiPhage for discovering new phages and then ProxiLink is for looking at the transmission of antibiotic resistance in complex microbial communities.

 

00:05:33:11 – 00:05:49:12

Speaker 1

And so, the focus of today’s talk is really going to be on one of the properties of this technology. It allows us, you know, we really want to understand the structure of chromosomes, the structure of genomes. This is extremely important in the medical space, right?

 

00:05:49:12 – 00:06:07:18

Speaker 1

There is a whole army of diagnostics that have been designed specifically to look at the structure of chromosomes. But these diagnostics of the day of today, the sort of the most well adapted ones, you know, they’re limited, they’re limited in scale, they’re limited in throughput, they’re limited in their resolution.

 

00:06:08:01 – 00:06:27:07

Speaker 1

And our technology can solve these problems to a large degree. And that’s what we’re going to be displaying today. So, we recently launched a method called CytoTerra It’s a new platform that we’ve developed that enables us to leverage this technology to really benefit folks who are trying to do cytogenomic testing.

 

00:06:27:18 – 00:06:30:19

Speaker 1

And that’s what Jill is going to talk to you next.

 

00:06:32:20 – 00:06:58:09

Speaker 2

Thanks, Ivan. I want to start with some basic background context as to how our platform plays a role in advancing precision medicine focused research and diagnostics. And it’s really built on this fact that we know very well, which is genomic and chromosomal rearrangements are drivers of every aspect of disease, from etiology to prognosis to therapy selection.

 

00:06:59:00 – 00:07:22:03

Speaker 2

And we see proof of this in long standing examples like the 9:22 translocation and CML shown on the left and those patients’ response to a very specific therapy Gleevec. We also see in an example like the spectral cure type tumor on the right, where there are likely many abnormalities as opposed to one specific abnormality contributing to this

 

00:07:22:03 – 00:07:46:16

Speaker 2

tumor’s development. And those are examples in cancer, but we know these rearrangements play an equally important role in many other diseases and conditions like infertility, recurrent pregnancy loss, developmental delay, and those are just a few. So, we have a collection of or genomic methods we use to try and help uncover these genomic disease drivers.

 

00:07:47:01 – 00:08:07:19

Speaker 2

These are karyotyping or chromosome analysis, FISH, and microarray. So, among these current solutions, we have a combination of high and low throughput approaches, high- and low-resolution approaches. But even with this range of resolution and throughput, each solution still has its drawbacks.

 

00:08:08:15 – 00:08:34:00

Speaker 2

For cytogenetics, we need live cells to grow in culture. We also need highly skilled personnel to do the analysis and interpretation of the results. For FISH, we need advanced knowledge or advanced suspicion of the abnormality. With Array, it’s difficult to detect things like balanced rearrangements inversions, low-level mosaicism

 

00:08:35:01 – 00:08:55:05

Speaker 2

So collectively, we’re trying to balance these limitations such that we get as comprehensive of a view as possible with respect to the size and type of abnormalities that may be present. And typically, to get that comprehensive view, it’s necessary to use these methods in a sequential format.

 

00:08:55:13 – 00:09:15:09

Speaker 2

So, when we look at that in terms of workflow and timeline, we end up with a resource intensive, very long, very expensive cascade testing approach. And this is where our Phase Genomics platform has a major impact in that it offers an efficient, streamlined workflow.

 

00:09:15:21 – 00:09:37:19

Speaker 2

And that’s because ultra-long-range sequencing can provide the large structural and copy number variation detection capabilities that we find with cytogenetics, along with the molecular precision of FISH and Array, all in a single assay. So, we’re eliminating the cost and time associated with the current cascade approach.

 

00:09:39:23 – 00:10:01:05

Speaker 2

Ivan touched on the technical aspects of ultra-long-range sequencing earlier on. But at a high level, we’re able to leverage that method’s unique capability to capture the physical proximity of DNA sequences in the genome. We then use our proprietary analytic software to convert the proximity counts to genomic distances.

 

00:10:01:12 – 00:10:31:17

Speaker 2

And as a result, we’re able to detect a wealth of abnormalities like balanced and unbalanced translocations, inversions, insertions, aneuploidy, and a lot more. And these capabilities are part of a comprehensive sample-to-report service workflow, with results ultimately being returned using standard ISCN in sequencing nomenclature and returned in a familiar clinical style report format.

 

00:10:32:16 – 00:10:53:02

Speaker 2

Well beyond the report, we’re creating a valuable data resource for novel variant and biomarker discovery. So, does it really work? Yes. And here is some data from proof of concept work we conducted with an academic health system clinical genetics lab.

 

00:10:53:21 – 00:11:14:07

Speaker 2

And in these 100 plus samples, we see our Phase Genomics platform not just meeting, but exceeding the detection capabilities of the current set of genomic approaches, with some low-level translocations not previously identified being detected. And we’ve had similar success with other sample types.

 

00:11:14:13 – 00:11:31:16

Speaker 2

And you can see a list of some of those here. Everything from whole blood and cheek swabs to POC tissues. But it’s not just compatibility with numerous sample types that makes this platform so flexible. It’s flexibility in sample condition as well.

 

00:11:32:05 – 00:11:50:22

Speaker 2

The platform works with fresh samples, frozen samples and very notably, it works with FFPE samples. And here’s just a small representation of some of the FFPE tissue types we’ve worked with in the past. So why is sample type flexibility compatibility…

 

00:11:51:02 – 00:12:16:14

Speaker 2

Is detection capabilities particularly meaningful to reproductive health in oncology? Well, to start, there are some sample related challenges in these areas. Obtaining fresh sample material for cell culture is difficult in POC samples, for example, this tissue is often non-viable, with very high failure rates for tumor and bone marrow samples.

 

00:12:16:20 – 00:12:36:03

Speaker 2

There’s often a limited amount of sample to work with, and the cells are not necessarily unviable, but they’re disease cells that are often very challenging to work with. Formalin fixation and paraffin embedding are also prevailing collection methods for these sample types, so cell culture is immediately out of the question.

 

00:12:36:20 – 00:13:03:08

Speaker 2

And then there are concerns about obtaining sufficient quantity and quality of the high molecular weight DNA that’s needed for things like Array and many NGS assays. These are also areas where balanced rearrangements play a significant role. There are cryptic translocations or seemingly balanced rearrangements in areas of visual homology that can be causative, so knowing if something is

 

00:13:03:08 – 00:13:31:19

Speaker 2

truly balanced is critical. We also know that gene fusions resulting from balanced rearrangements drive cancer and tumor development. So, in the end, these challenges present as missed opportunities, opportunities to uncover diagnostic and prognostic information, to discover biomarkers for therapy and treatment development, and to make genotype phenotype disease associations to further disease understanding.

 

00:13:33:24 – 00:13:54:10

Speaker 2

So, in comparison to the current cytogenetics methods, our Phase Genomic platform can avoid these and many other missed opportunities by offering genome wide simultaneous detection of the multiple types of genomic rearrangements that cause and characterize disease, and it can do so in a single assay.

 

00:13:59:20 – 00:14:11:04

Speaker 2

The platform has capabilities well beyond what we expect of our current cytogenetics methods. I’m going to hand things back to Ivan so he can talk about what some of those expanded possibilities are.

 

00:14:14:18 – 00:14:29:20

Speaker 1

Thank you, Jill. So, as you have just seen, this platform is very useful in the field of cytogenetics. But there’s more there’s a lot of things you can do with it beyond just sort of an improved way of conventional testing.

 

00:14:30:14 – 00:14:57:20

Speaker 1

one of the main challenges in oncology is that while you know there are obviously so many different cancer types, only a small subset of available cancer samples get processed, cytogenomically and get analyzed by cytogenomic assays. And the reason is that the vast majority of cancer biopsies in cancer samples are stored as FFPEs.

 

00:14:58:03 – 00:15:20:07

Speaker 1

They’re stored in formalin fixed paraffin embedded format. And what that does is that kills all the cells and also ruins the DNA for long read sequencing for optical genome mapping. And so, it makes most karyotypic assays and large-scale structural analysis virtually impossible.

 

00:15:20:21 – 00:15:31:04

Speaker 1

And this is one of the things that our technology can overcome. So first, let’s take a look at what this data looks like we’ve been talking a lot about. So, the technology and what it can do? But here’s what.

 

00:15:31:16 – 00:15:54:05

Speaker 1

At its core, here’s what the data looks like. When you plot this type of ultra-long-range sequencing information, you can you generate these sorts of maps these heatmaps. Imagine if you’re not familiar with this, imagine a just a matrix where an x axis and the y axis you just lay out the chromosomes like left to right

 

00:15:54:19 – 00:16:18:03

Speaker 1

and you’re seeing this coordinate system. This is chromosome, you know, 1, 2, 3, 4, 5 and chromosomes along this line. And these boxes are showing you how much interaction there is within that combination of coordinates. So, this heat inside of this box tells you that there’s a lot of interaction between chromosome two and chromosome two other parts of

 

00:16:18:03 – 00:16:33:07

Speaker 1

the same chromosome. They’re touching each other because they’re close. But there’s not a lot, for instance, between chromosome two and chromosome four. Right? But then if you look at a cancer sample like this one, you will see that there is this hotspot in this box.

 

00:16:33:07 – 00:16:48:05

Speaker 1

And what that means is that this area of chromosome two and this area of chromosome four are touching each other way more than they’re supposed to. They’re closer together. So, this was caused by a translocation and there are different types of these events.

 

00:16:48:06 – 00:17:07:20

Speaker 1

Sometimes they look like squares, sometimes they look like bow ties, et cetera. We have essentially trained the analytics, right, we’ve built this A.I. that recognizes these things, and that’s how we can generate these. These karyotypic reports, karyotype maps, but we can do this in FFPEs.

 

00:17:07:24 – 00:17:26:18

Speaker 1

And the reason why we can do this in the FFPE is because the first step of our method involves fixation with format with formaldehyde or formalin, which is what the f is in FFP. And so, we’re able to not only generate these kinds of cytogenetic profiles on fresh frozen tissues and cells and these sorts of things

 

00:17:26:23 – 00:17:44:22

Speaker 1

, but also, FFPE slices and even a single FFPE slice can generate a really cool complex karyotype. So, this is an example from one of our collaborators. This is a solid cancer. FFPE slice from a solid cancer is just a slice.

 

00:17:44:22 – 00:17:59:23

Speaker 1

You don’t need to consume the entire FFPE block. Everything works with sort of how people are used to looking at it, and you can see again, in this case, the data is shown in a different color. It’s now orange instead of blue, like in the previous slide.

 

00:18:00:09 – 00:18:20:21

Speaker 1

But basically, again, these boxes are the chromosomes and these little shapes. These events out here that are marked by black arrows represent the structural chromosomal aberrations within this FFPE slice. And so, you know, there’s there are these little bow ties and squares like before, and you can sort of divide them.

 

00:18:21:13 – 00:18:30:15

Speaker 1

Here’s what they look like when you when you zoom in. If you were to kind of visually analyze it, this is what they would look like. Of course, we use software, but you can actually look at them and see them with your eyes.

 

00:18:31:19 – 00:18:46:23

Speaker 1

And so, this is what a balanced translocation looks like an unbalanced an inversion because this technology is sequencing based, Illumina sequencing based. It allows you to do all the other things that you do with Illumina so you can detect deletions and copy number changes.

 

00:18:46:23 – 00:19:10:18

Speaker 1

You can detect amplifications; you can detect aneuploidy and other similar things. And so, you can generate these really complex karyotypes right off of FFPE without sort of, you know, in the very in a very manageable way. And so, what we’re going to show you in this video here is a comparison of a data set from a fresh

 

00:19:10:18 – 00:19:28:11

Speaker 1

frozen lung cancer sample and an FFPE matched sample from the same biopsy. And so, what you’re looking at again is just like before the boxes in the middle of the chromosomes and the events out in sort of in this yellow space.

 

00:19:28:16 – 00:19:43:15

Speaker 1

These are your translocations and other karyotype aberrations. So, we’re going to zoom in. This is being visualized in a tool called high glass. And so, what we’re doing is we’re sort of zooming in in sync with a fresh frozen in an FFPE sample.

 

00:19:44:03 – 00:20:06:07

Speaker 1

And when I hope you can see is that we’re able to even in a FFPE sample, detect really, really sort of crisp, large scale structural rearrangements. And this is going to zoom in on its kind of just so you can see the sort of the beginnings and the ends of these things, and we can then map

 

00:20:06:07 – 00:20:17:01

Speaker 1

them to, of course, their genomic coordinates and what you’re looking at here is this is the entire genome. And so, you can see there’s lots of things happening here. There’s some of them are small, some of them are big.

 

00:20:17:11 – 00:20:39:20

Speaker 1

So, this allows you. This method allows you to reconstruct high quality karyotype maps specifically for FFPE samples, as well as for any kind of fresh frozen sample. And finally, what I’m going to end with is this technology because it is based on Illumina sequencing.

 

00:20:40:01 – 00:20:55:14

Speaker 1

It is compatible with target capture methods. So, if you are looking for if you’re looking for specific snips, if you’re looking for mutations, if you’re looking for a loss of heterozygosity in specific regions, you can actually pair the two methods.

 

00:20:55:20 – 00:21:15:17

Speaker 1

You can use pretty much any capture panel out there. They all work extremely well with this technology, and that allows you to do simultaneous snip profiling looking for specific mutations in specific genes while also generating a structural map of karyotype for your given sample.

 

00:21:15:17 – 00:21:39:02

Speaker 1

Be it fresh frozen, be at cells, be it FFPE directly out of one sample, so you can combine a target capture panel and a cytogenetic work, up from the same sample with this technology. So just to summarize and finish off this talk, what we’ve shown you is that applying ultra-long-range sequencing to various biological samples

 

00:21:39:09 – 00:22:00:14

Speaker 1

is basically a really useful way of enhancing your cytogenomics game. It’s a scalable platform for cytogenomics. It’s simple. It can be performed in your lab. You don’t need a special machine for this. Aside from Illumina sequencers, which can which are sort of, you know, pretty common these days, we provide both services kits as

 

00:22:00:14 – 00:22:20:07

Speaker 1

well as companion cloud-based analytics, so you don’t have to sort of figure out your own computational pipeline. We integrate both the analytics as well as the molecular methods. It works on all sorts of difficult sample types. It works, and if it works on cheek swabs, it works on all sorts of samples that are usually very difficult

 

00:22:20:10 – 00:22:36:07

Speaker 1

to process by traditional cytogenetic methods. As I mentioned, you don’t need to make sort of buy a special machine for this. You don’t need high molecular weight DNA, so it’s a much easier way of generating large scale cytogenomic data.

 

00:22:37:08 – 00:22:52:16

Speaker 1

If this is something that you’re interested in, please let us know. And the reason why we’re giving this webinar is to announce sort of our early access program. And so, we are recruiting folks to do all sorts of cool research with us.

 

00:22:53:00 – 00:22:58:19

Speaker 1

So, this is of interest, please. You can scan that barcode. You can go visit us on the website and shoot us an email.

 

Inside the Microbiome Startup Industry

 

The microbiome is a very special opportunity because it allows you to create products that potentially have the efficacy of a drug, but the safety of a probiotic
-Colleen Cutcliffe, PhD

 

The Fall 2021 Genome Startup Day event, Inside the Microbiome, took a deep dive into the origins of several microbiome startups. Starting with a fireside chat, Ivan Liachko, PhD, cofounder and CEO of Phase Genomics, and Dr. Christopher Mason, Professor at Weill Cornell Medicine and cofounder of several startups, discussed Mason’s passion and recent projects relating to the microbiome. From children licking their way around their environment to sending fecal samples into space, Mason described his journey into the emerging field of the microbiome. He continued onto some of the early challenges in transitioning from academia to industry and shared his advice to any graduate students attempting to do the same. Mason also noted the improvements being made in this field, making it easier for startups to collaborate and progress.

 

“It’s become much more of a startup-friendly, entrepreneurial ecosystem in most academic centers”
-Christopher Mason, PhD

 

Next, Dr. Kirsten Sanford, host of This Week in Science, led the panelist discussion. Colleen Cutcliffe, PhD, cofounder and CEO of Pendulum Therapeutics, described her motivation to begin a microbiome company. She began with an anecdote about her daughter overcoming illness and inspiring her shift in focus from publishing papers to creating health solutions. Momchilo Vuyisich, PhD, cofounder and CSO at Viome Inc., shared similar experiences he had aiding people to improve their health in miraculous circumstances. Coming from a different field of study, Nick Greenfield, Head of Microbiome at Invitae, described his experience breaking into the industry and how he founded his initial startup, One Codex.

 

View the event recording below for the full conversation and more insights into the world of microbiome startups.



Stay up to date with Genome Startup Day on Twitter and watch previous events on the Genome Startup Day website.



Transcription

Ok. Welcome, everybody. We’re going to get started here for today. Sorry, I had to close my other tab. So good afternoon, everyone. My name is Kayla Young, and I am the chief operating officer at Phase Genomics. Thank you for being here.

Our next Genome Startup Day event. So, for those of you that are new to our events, Genome Startup Day, it’s designed to be a community building catalyst for genomics startups, founders, investors, service providers, media, and jobseekers. So please stay connected with us via Twitter.

@GenomeStartup I also put that in the messages and keep up to date for future events so quickly for kind of some run of show things and housekeeping. We will do question and answer at the end of both the fireside as well as the panel.

So please put those questions into the chat box on the right side of your screen. Additionally, for every question asked will be entered into win Phase Genomics socks, so we will announce those winners throughout the sessions. But I will follow up after to coordinate that.

So, ask those questions and join the conversation. And then finally, last but not least, I would like to extend a very big thank you to all our sponsors that make this happen primarily s2s PR, which helps put on these events for us, but also Agilent, Illumina, Pacific Biosciences, Alexandria LaunchLabs and CoMotion without this sponsorship.

This would not be possible. So, with all of that behind us, I would like to introduce our fireside chatters and my boss, Ivan Liachko, CEO and co-founder of Phase Genomics, who will be talking with Dr Chris Mason. So, Ivan over to you.

Hello, everyone, thank you for coming. Thanks, Kayla, for the intro. As you can see by my fancy attire that we’re having a fireside chat and I’m very lucky today to have with me Chris Mason, who many of you are familiar with.

Chris Computers Chris is an Associate Professor of genomics, physiology and biophysics at the Weill Cornell Medicine and director of World Quant Initiative for Quantitative Prediction, as well as an affiliate of Memorial Sloan-Kettering Cancer Center. Rockefeller, Harvard Med School, Yale Law School.

And there’s like three more pages of this stuff. If you’re not familiar with Chris, Chris is super engaging speaker. I’ve seen him talk many times at different conferences. He addresses really cool topics, most notably his interaction with Nassau and Nassau, not Nassau, NASA and the others, the space poop work he’s done with Kelley twins and

others. And of course, recently a lot of microbiomes of sort of cities and built environments. He can see, I’m just trying to read something. He’s got like 1,000,000 awards. He has been on like ABC, NBC, CBS, Fox, CNN, PBS, Nat Geo.

He’s also one of the reasons why I like to have. I like to, you know, I wanted to have Chris on here is because the purpose of this event is really it’s a startup event, but it’s a little bit different because the goal was not so much to educate people about, like how to raise money and how

to do startup mechanics. But really about that transition for scientists, that has to happen at some point between academia and industry. Like at some point we as geneticists have to come out of our earlier kind of academic shell and decide to spin out companies.

And there are so many challenges. And this event was really about talking about it, not about so much educating you, how to do it and filling out the forms and IP and all that stuff. But really like, what’s it like?

And what’s cool about Chris is that he’s a super accomplished faculty. He’s doing tons of science. He’s in the news all the time, but he’s also very involved in the commercialization of technology is associated with lots of startups, and that’s why I really wanted to bring him in here.

A lot of times what we do is we have founders who a lot of times they’re like juniors and we get their perspective, but of course, they interact their faculty all the time. And so, I want to know what it’s like from a faculty perspective and faculty, as Chris, as you know, range all over the place from

being super startups and commercialization to being straight up hostile to it. And like, you know, and so we want to just talk about it and like, get your opinions. And obviously, if you were super hostile, I wouldn’t have.

Right, right?

So, I’m assuming you’re pro. So, so yeah. So, let’s first off, this episode is about the microbiome. You know, why is it about the microbiome? The microbiome is cool. I work with the microbiome, and I organized the show.

So why do you do so much microbiome work? What’s like? What’s your favorite thing about it? Like what? What draws you to that particular topic?

Yeah, the number of things, actually. And can you hear and see me? Okay, sounds amazing. OK, great. So, a few things. The real inspiration came from two events that happened around the same time as that one. I just became a father and saw a lot of microbial interactions from a new lens, which is just, you know, infants

crawling on the floor, licking things, putting everything in their mouth. I actually talked to our daycare when we first dropped her off and said we should do an experiment. There’s a lot happening here in terms of microbial transfer.

And of course, then I realize I immediately was that creepy, weird scientist. That’s like, why is he planning experiments on our children so we didn’t do that because that would have been a little weird, but the thought never left my head.

The other thing that was happening at the same time is we started doing a lot of whole genome sequencing clinically in 2011 2012, and there are always fragments of DNA, even if you know, especially you get from a skin sample.

But even sometimes blood samples that didn’t match up to the human genome part of it because the human genome is incomplete. But also, you will have microbial sometimes contaminants that are there, but sometimes actually mediating biology. And they’ve recently been found inside of tumors.

They’ve been found, of course, in gut samples and skin samples, but even circulating in blood. We now have a company you one of my companies, Biotia is working on ways to sequence microbes from anywhere, including CSF or from things that normally have blood that you wouldn’t think would have that much unless you’re really sick.

There’s actually trace signal that’s there every time you sequence a sample, that’s you human microbial really in any kingdom of life. So, as I became more and more of a clinical geneticist in practice and also in startups, I just began to realize you have to be really kingdom agnostic to do the best possible science.

So even if you’re a computer empirically, wonderfully, trained human geneticist, if you only look at the human genome as a geneticist, you’re actually really crappy human geneticist because you’re missing a lot of biology. So, to understand health, wellness, disease trajectories of any of them, you have to look at it from a kingdom agnostic or kingdom inclusive view

across all domains of life.

Yeah, no, it’s really, it’s really cool. Like the thing that drew me to it, honestly, was that just the fact that if you think about like, you know, if you think about diminishing returns of discovery, right? Like we’ve done a lot of work on cancer, we’ve got a lot of work on human biology.

But like if I see sequence, if I scoop a little thing of soil right outside my like, it’s all new. Like, it’s like an unknown and it’s not like we invented it. It’s always been right. Like, we just.

Now.

Everything we do, we just have not had the tools to really to really measure it. Yeah. What about like the flashy projects? So, like, what was your favorite thing about the space poop? And like, how long did it take to like, get into that whole thing and become like, then that’s like, are you?

I’m assuming the next stage is going to be terraforming Mars with just sending them like poop and dumping it on there. Yeah.

Matt Damon. Yeah. I mean, it’ll take a while, but it actually did just publish a book called The Next 500 Years, which is a five-year plan to actually get people on to Mars and other planets, which involves a lot of microbial engineering, potentially even human genome modification or engineering to make it feasible.

So, I think there is a lot that we can do that we’ve just learned the tools do some of the genetic manipulation. Most obvious is CRISPR or some of the new Amiga systems that can do gene editing, but also just the catalog of genetic what’s in our DNA toolbox of just functional elements from all microbes.

Other species that we can use and deploy is getting bigger every day. And that’s kind of it’s really exciting as we are. We’re still in in this discovery phase, but it’s ramping at a super exponential pace. So, we can really sort of imagine doing this for, you know, anything from as simple as microbial monitoring on the space

station, which we’ve been doing for a few years. And most recently, I know Jack Gilbert, Robin, I’ve done some sampling up there as well. So, like more and more teams are thinking like, well, what can we learn from the microbes in space when we bring them back down and sequence them or even sequencing in space, which we

published a few years ago? They’re actually different. They evolve quite quickly. It’s a unique selective environment, which, you know, it’s not too surprising when you think about it. But you know, everywhere we look, including the space station, there’s new things to discover.

And I think a lot of the space projects are my favorite because I consider it my life’s work to try and get that goal.

But we’re like, I got hit by a bus tomorrow. At least I would have sequenced poop in space.

That’s right. That’s right. At least I got that. Check that off my list.

And yeah, the first time we sequenced the platypus, that’s what I said to myself. If I die today, I can say we sequenced a platypus one.

Funny you mentioned there is a bus rule in the labs that if you get hit by a bus, the work has to continue to document that. We’re very careful with the lab notebooks. We call it the bus rule in lab.

Which is that’s a that’s a that’s a good one. Yes, testing it might be a little hard, but what do you think will be the next thing? The next? What’s the next big thing in the space?

We just finished the inspiration for mission, and now we’re planning some other missions with Axiom. I going to have its own private space station by 2024. So, I think I think the next big thing is this commercial space sector, which is kind of a new space race.

So, we work with the medical ops team at Space X a lot over the past nine months to set up the first aerospace biobank and set up some of the very first protocols for sampling for private astronauts. What’s kind of amazing now is it’s going to be like Axiom is just space station.

So, if you want to do anything up there, as long as you can afford it, you can fly it up there and do whatever you want. So, it’s in the ranges of tens of millions of dollars, or sometimes hundreds of millions of dollars, depending on how long you want to go up there.

But you know, if you can afford it, you can go do whatever you want up there. So, we’re working. Yeah, we’re working on a bunch of interesting missions where one person wants to go for 500 days and stay in space for the longest time ever to simulate a trip to Mars and back.

Basically, other people want to do manufacturing in space. A lot of people want to do, you know, microbial engineering, even in space or organoid work that’s already happening. So, I think there’s a lot in the space sector is opening up a lot and it really was hard to get up there and difficult before.

But now it’s going to be it’s going to be pretty routine, which is pretty cool. So, if they have any experimental thing to do, it’s possible.

The space. All right, let’s talk about startups. So, as I mentioned, you are super active and super successful. You have a lab. You know, how and why did you get involved with startups?

I got my first startup failed, which is important now. I think a lot of people feel like it was one called Genome Liberty, which is right after the AMP versus myriad decision in 2013. We thought, OK, now genes are no longer patented.

We should make it so anyone can sequence any gene they want. I want to like a run down the streets of Manhattan and say, you get a genome, you get a genome, you everyone get the genome like Oprah.

But I was just so. Saying it because it had really democratized access to people’s own genetic information, and so we started a company that was the beginning of kind of a direct-to-consumer genetic testing company like 23 and me but more focused on actionable genes like pharmacogenomics and cancer genes, which ended up this idea ended

up being something like what color genomics is doing other companies. But at the time, the FDA was really clamping down on DTC genetics companies. And so, we and they even been sending letters to 23 and me. So, I thought at that time with a newborn child and a fairly young professor, do I spend a lot of time

and regulatory back and forth with the FDA, with the company that has very little funding? We did a crowdfunding campaign to get it off the ground and got some money, but at the end it was just some point to do a startup.

You need more than one or two people who are doing it part time to really get off the ground and what’s often called fire in the belly. And some of that’s like, I’m going to leave my job and have this be my job.

You don’t want to get to faculty doing it like 5% of the time. It’s never going to take off, right? So. So but the concept of it I really like is that there are ways where you can’t do it at an academic lab.

And academic labs are great for many things, for a lot of the pure discovery, pure development of new protocols, but to scale them or to get them out to the mat, a large number really have to do in a company setting.

You have to really, you know, like you can’t do, you can’t work with 1,000,000,000 people or get things a vaccine, for example, to 1,000,000,000 people from a small academic lab or even a big academic. That right, it’s just not it’s not worth for.

And so, I really start to think more about how do I really launch some of the things we’re tinkering with in lab and get them into a commercial setting? And that’s actually what led to Biotia was getting all the metagenomics work we were doing.

How do we make it so we can use this as a diagnostic and really get it to market? So, I think it’s a classic pinpoint let it pay pain point. And at what point can we go from a cool concept in the lab?

It’s working. We know it has capacity to change how we treat a certain disease or do diagnostics, but you have to at some point either set up as an LDT in your own CLIA lab or actually start a lab if you really want to go in that direction.

So yes, we’re going to get it be. It’s basically if you look around the world and the thing that you want doesn’t exist at some point you just have to either buy it or build it, and it didn’t exist, so we wanted to build it.

That’s awesome. And I think. There are two points that you made that I think are super important for our audience. one is that Chris Mason had a startup that failed. one of the things that startup founders and just startup people in general deal with all the time is this bias of like, you only hear about the successes

, but actually, failure is super common. And so, anyone who gets anywhere near what doesn’t seem like success starts having all these anxiety issues right? And so, I wanted to highlight that like, you know, like, it’s normal. These are every startup is an experiment, right?

And you don’t know what’s going to happen and you think, you know, you think you’re going to nail it out of the park, but you don’t really know, ever. And so just highlighting it for people in the audience maybe who are considering or thinking about it, like it’s normal, it happens and as part of the ecosystem.

And then the other thing that you mentioned that was interesting to me is this prime mover idea is that like you like you need; you need people who are going to go all in at some point.

I also when I started phase, like I kept one toe in academia for a long time. Eventually, I had to jump. And you know, and the faculty are generally the ones who do the jumping because you guys have good, solid jobs and you’re right.

Because you’re tenured faculty like, well, why would I give up this literally like guaranteed lifetime job? And so, it’s got to be. And also, I have to look for people who left my lab and go to start companies.

I also it’s going to be a good opportunity to look at an actual capitalized company where they’re going to do a real job, not, oh, I think we’ve got some money will go look for more money later. You really have to make sure you launch with a full, full tank when you hit the road.

So, so let’s talk about that a little bit, because I guess I mentioned sort of the relationship between faculty and students who go into industry can be touchy sometimes and sometimes people, they want to, you know, sometimes they want to start a startup, but sometimes they just want to go work for a company like, you know, work

for Agilent or Illumina or something. And how do you like, how do you what sort of. Interaction, do you have how do you relate to students who are doing that kind of stuff? Like what do you do to encourage and discourage them?

You know that kind of stuff.

I think mostly they do. I mean, the interactions depend a lot on the person, of course, it’s a little everyone’s a little unique snowflake in a way, but the one thing I do is I discourage people, feel like a first-year grad student and think, oh, I’ve heard about startups, I want to make my own company.

I think, well, you know, give it a I mean, you can’t like you could be the next Steve Jobs or Bill Gates, but the odds are that you’re not like, you know, you may not need to finish college or grad school and just jump right in, you know, maybe, but you got to play the odds a little

bit. And then also, you can still do some of the tinkering and development and IP development at. I mean, I think most people I encourage them say like file patents when you’re a grad student or postdoc. The university loves it and then you can license that IP to start.

A company in the UK have a good foundation for the company rather than. I have an idea and I need $10 million to get off the ground. If you actually have IP, investors will like that a lot more. Not surprisingly, and so will your customers because of something that they’re using, that’s unique.

So, I think the I encourage them to file patents encouragement to not do their first year of grad school, but that they should, you know, when you’re getting towards the middle years to start to think about if they really want to go that direction.

So, try to be as encouraging as I can. And you know, I actually wish people had told me, hey, if you have an idea, go meet with the tech transfer people out of university because they can help you file patents when you get out to the private market.

Filing patents is bloody expensive right after it’s 20 to $50,000 per patent prosecution. Depending on how complex it is. The university does that for you, of course. Then you have to pay them later to license it.

But at that point, somebody else was paying for it. So that’s another really, really good point. You know, when you’re and maybe this is helpful to someone in the audience. But if you don’t know if you’re a grad student or postdoc, and you invent something the university owns that invention or what that means, is that they

will be the ones paying for patenting it if you convince them that it’s worth it. And so, yeah, it’s hard to imagine a scenario where it’s you shouldn’t patent.

Even for it is like, I don’t know if my idea is that good, but just go pick up the phone and call the patent attorneys who look at this, and you’d be surprised how often things are really straightforward can lead to a patent.

Yes, because no one’s gone for them.

Yeah. And if nothing else, you learn a lot of stuff. Like the other thing about startups is that like when you go through the process, you just like the first six months is like the most learning intensive process period of your life.

Like you’re learning things that you’ve never heard about before or maybe you’ve heard of. Have no idea what they are, you know, and patents is one of those things, at least, you know, it’s something you should be aware of.

It’s part of our ecosystem. What do you think like, what have you seen in terms of the general ecosystem, like for other labs? Like what have you seen in terms of kind of how folks, you know, you know, New York is very high tech, obviously.

Like, what do you how do you see the shift happening like that, like you told your own story about sort of startups and interacting with students? What about everybody else? Like, are more faculty becoming into it? Or like, what?

What do you see?

Yeah, it really is. It’s become much more of a of a sort of startup friendly, entrepreneurial friendly ecosystem in most academic centers that I’ve seen, especially in the past five or six years. You know, there’s even a dean who’s just about biopharma collaboration and entrepreneurship at Cornell, at the med school.

There’s also one at Cornell up in Ithaca. So, there are, you know, now dean level appointments of people who think we should just encourage this, encourage Google to come up with ideas. Also, the NSF and the NIH and DARPA all help support startup companies.

So, NASA even has something like an SBAR fund, which is a small business innovation or research award, but it’s a NASA version, so almost every federal agency really applauds and encourages people in academic sites to come up with an idea, get it capitalized, get it off to market, and we’ll give you grants for it, non-dilutive capital

coming from the government to help get your company going. So, I think that’s always been there. But I think in the past few years, you know, 15, 20 years ago, there was much more of a, you know, academia over here in pharma and industry over there, and they shouldn’t, you know, engage with each other.

But I think we’ve just realized there’s a lot more to be done that can be done faster if you do it together. So, I think there’s a lot more collaboration coordination between academic medical centers and industry and pharma and startups.

And it’s gotten it’s encouraged. You know, people, you know, encourage entrepreneurship in a way that I’ve not seen. I feel that wasn’t really the case seven or eight years ago in New York, in particular, is now a multiple incubator startup hub.

There’s Harlem, Biospace Spaces, Alexandria Labs, there’s cure building that just launches. You know, all these spaces, the bio that’s now the one where there’s a lab space. You can get a startup, get some space, get going and have a startup company.

Yeah. So let me do let me do a couple of questions from the audience. So, I have one. So, following up on the patent question, if the university owns a patent, then how do you build a business on that?

So, I mean, there’s a technical answer, which is you start a company and then you get a license from the university. But sort of. You know, follow up on that, like, what do you guys, how much work and maybe how much resistance have you seen, like if somebody’s getting something via Cornell and then they want to

go find the company? How difficult is it to get a license? That process can also be touchy sometimes between.

Yeah, see this question. And it does depend on the university. Generally, they will. They actually are much happier, more happy to file a patent for someone if they know that you either have an I.D. to make a company or that you’ve already got a partner with the company who’s interested in your invention.

So, I think they encourage that. But then you do have to license it and the university could. It’s like any negotiation for any piece of property, like buying a house or a piece of land. The negotiation could break down.

They can give you a bad deal, or you could be entrenched into the university, and they don’t have to. You know, it’s like any property. They don’t have to give it to you. They could give it to someone.

They could have an exclusive right over here and then no one else can have it. But normally, universities like to have multiple licenses because it gives them more money. At the end of the day, the more money that comes in, the more they can do with other investigators and other patents.

So, it always just depends on what you want to negotiate for. You know, at a certain number of revenue that some things kick in or a certain volume of sales that you can, everything’s negotiable. But the university that is the caveat is that if they own it, they own it, and you have to negotiate with them

. one distinction is Cornell Tech is where the tech school is. It’s and also just in New York City. On Roosevelt Island, they allow fully transferable IP, even though they’ll file it for you. Like, for example, Biotia. We can take a look at it.

We found when we spun the lab out of Cornell Tech, and it’s allowing a fully transferable IP to the company to then be selected. The company got sold and exit, which is very unusual, but it’s very progressive for Cornell Tech to do this to allow you to bring that fully bring IP, not just the license, but actually

take it with you. So that’s the only place I’ve seen that done before. So. But it is possible to do.

That’s cool. And how much? So, the question sort of sort of how much development is needed to get into this market, like, is a patent enough? Do you need a patent to go in? Like is it required? It’s not a question I get sometimes is how much IP protection do you need?

This trade secret.

Off.

Where it’s as various kinds of IP, there’s patents which most people know about, but there’s also just trade secrets. It’s up as a form of intellectual property. It’s obviously less clear what it is when you have a trade secret.

But Coca-Cola has a trade secret like no one actually knows the coke form, except for a few people that originally were sniffing cocaine. But now they just have a lot of sugar water. But you know, it was originally cocaine.

in Coca-Cola. So, there’s ways you can have a, you know, something that’s widely used, but no one knows exactly you have. And you know that that is a form of IP.

And one of the reasons I kind of asked that is because a lot of people don’t realize you don’t have to have a patent to start a company. You can start a company doing PCR for people like you can start a company selling pencils you can say you don’t need, you know, like there’s a lot of things

you buy from companies with Qiagen and like a lot of them, don’t have IP on them. And so, you don’t actually think about it as just like all patents. But it’s really about invention and developing technology and moving the space forward.

OK, let me get one more. OK? This is a good that’s actually will be we’re running off a time. This would be a good closer. How do you educate the public on this space? Like, you know, yeah, microbiome space is full of sort of fact and fiction mixed together, and it’s super tempting to get caught away, caught

in like the just the hype of the microbiome and overselling the microbiome. You know this ball and how do you keep it, keep it grounded in reality, but at the same time, interesting.

I do. Yeah. And you know, I myself, I think everyone, it’s easy to get excited because there’s so much you can discover so quickly for the microbiome and research and clinical approaches. But it’s like any bit of science.

It’s anchored on reproducibility and independent validation of whatever you think you’re seeing. So, you know, the placental microbiome is a great example of what people think. They see some things, but if it’s not replicating how sure that it’s real.

And I think you have to temper your enthusiasm with really good controls, positive negative controls like any experiment and independent validation of it. So, I think, you know, it’s not like you need any magic. It’s the same principles of good science in any field is just replication and independent confirmation.

You know, intra and inter lab validation and that lets you know that it’s real. And so, I think, I guess and using multiple methods to assay whatever your question is, which is also important for way to confirm what you think you’re seeing.

But we’ve published a lot of paper showing that depending on what tool you use, you get very different results for metagenomics processing or how you clean up the sample. How you fragment the sample is well known biases at every stage of collection, analysis, processing and interpretation.

So, you just do it many ways and make sure you keep getting the same answer.

Is there any? Just to close out? Is there anything that you want to tell? The audience like about the space and about startups and whatnot. You know, I can’t see who’s this, but it’s all like. So, is there anything you want to tell people a piece of advice?

Some sage wisdom?

I would say, you know, be pretty, you know, definitely file as many patents you can if you’re in grad school already said that, but I’d say be pretty fearless because you might think, oh, someone else must know the answer to this, but a lot of times no one knows the answer.

So, I would say be a little bit fearless and jump right in because there’s still so much that we don’t know, especially in the microbiome space, that you should jump in, and you can start a company with not with just an idea and a little bit of cash.

And many people did that during COVID. They just sold PCR tests that were already on the market and now they have a ton of money. So, you don’t need, you know, IP or that’s unique for a company that does help long term.

But you know, but the world needs a lot more people innovating on these ideas that bring things to market whenever you can.

Awesome. Yeah, definitely. Startup is very courage dependent and whatnot. So, thank you for coming, Chris. You will also be as a recipient of one of these amazing DNA socks.

They are fabulous. They’re very.

Good. The real prize. And I’m going to give one away right now to somebody in the audience. And that person is that person is Elizabeth Stewart. So, get in touch with Kayla afterwards. Chris, thanks again. We’re now going to go to our panel, and it’s been it’s going to be moderated by Dr. Kiki Sanford from

This Week in Science. And stay tuned and reach out to us if you have any questions and I’m going to give away more stocks at the end.

Thanks. Thanks, Chris.

Thank you. Thanks, Chris.

Next up, we are going to move along to our panel. So, I want to introduce our panel moderator, Dr. Kiki Sanford. Kiki is the vice president of public relations at Science Talk. She is the owner of Broader Impact Productions, and she is the host of the This Week in Science podcast, which I highly recommend and will

link in the messages. So, she’s going to introduce our panelists, and there will be another question-and-answer session at the end. So let me add them. OK, over to you, Kiki.

Thanks, Kayla. Oh, I just want to say thank you to Ivan and Phase Genomics and s2s PR for inviting me to be a moderator for this session. I am excited to be able to talk with all of these CEOs, founders, amazing scientists interested in exploring, launching and growing a startup in the human microbiome space for all

of us today. So, we are joined today by three founders who I will introduce right now. Colleen Cutcliffe is the CEO and co-founder of Pendulum Therapeutics. This is a company developing microbiome targeted medical probiotics. Nick Greenfield is head of microbiome at Invitae, the medical genetic testing company that acquired the company.

Nick founded the microbial genomics and bioinformatics platform one Codex. And finally, but. Not least at all, just the last on the list, Momo Vuyisich, which is the founder and chief science officer for Viome which describes itself as the world’s first and only at home m RNA test for precision nutrition, scanning gene expression to provide health and

nutrition insights. Each of these founders has a fascinating background and has taken different paths to getting where they are today, and hopefully we will be able to dig into what they’ve done, how they got there. And welcome to all of you for joining us today for this conversation and this panel.

first, I want to ask, Colleen, can you give us a little background, what was it that pushed you from what you were doing, a Ph.D. in biochemistry, having moved on to a postdoc and then into research in industry?

What pushed you into starting and founding your own company?

Well, thanks for having me on the panel discussions. Super excited to get to be alongside Momo and Nick. I haven’t seen anybody in years, but good to see you guys, at least on the screen. So, for me, when we decided to start this company, I was working at a DNA sequencing instrument company that had gone public, and

there was just a kind of fundamental new science around the microbiome that was in academia at that time. And it felt like the moment was right to be able to translate all that great academic work into products and at the heart of being able to identify novel products in the microbiome was DNA sequencing technologies and the ability

to analyze them. And of course, that was eight or nine years ago. We’ve come a long way since then and all the additional tools and technologies around understanding the microbiome. But at that time, it felt like me and my two co-founders had a leg up on really understanding how to use DNA sequencing.

And then at a personal level, as I started learning more about the microbiome, I realized that my older daughter had potentially some microbiome deficiencies of her own. So, she was born almost two months premature. And when you have a baby born that early, you get to see them for a couple of seconds, and they get taken away

from you to intensive care, which is where she spent the first month of her life hooked up to all these machines and monitors and receiving multiple doses of antibiotics. Not because she had an infection, but because that’s prophylactic.

They’re so fragile, they want to make sure they don’t get an infection. And around the time that we were starting this company, this publication came out that where they studied 12,000 children and saw that infants who had been systematically exposed to antibiotics below six months of age were also systematically more prone to obesity and diabetes as they

got older. And the Mayo Clinic recently repeated this where they showed that kids who are under two years old and have been systematically exposed to antibiotics were more prone to diseases later in life. Not just obesity and diabetes, but also things like celiac disease, ADHD.

And so, my own daughter was experiencing metabolism issues, and she was in elementary school at that time. And so, for me, I realized we had this technological advantage. We could create products that could help millions of people, including my own daughter.

And the microbiome is a very special opportunity because it allows you to create products that have potentially the efficacy of a drug, but the safety of a probiotic. And that’s really the promise of the microbiome. We’re all trying to realize.

That personal angle, too. There are so many of us who are wondering, you know, how we can, how we can use our personal ecosystem to our benefit and Momo. You also have taken a path from academia to research working at Los Alamos National Labs and into this startup industry.

Can you talk about what led you to make the jump?

I was really driven. I developed some kind of an early onset arthritis, ankylosing spondylitis, autoimmune. No one really knew what it was, but I was suffering for just over a decade, and I was able to cure myself with a diet switch.

It was all science based, and it’s a long story, but I really was entrepreneurial at all times, and I really wanted to use my scientific skills to improve humanity and not just published papers in an academic setting. And so, I switched my career, and I worked really hard with my awesome team to develop some foundational technologies that

we then I basically did. What Ivan and what was discussed earlier, which is we patented the technologies at my previous institution and then I left, and we license those. And so that’s what we’re using today. So that worked really well.

And yeah, so I really want to apply a systems biology approach to all chronic diseases and cancers and find ways to prevent them instead of to treat them. That’s why I was formed.

That prevention through ongoing health and nutrition being a huge aspect of that for sure. And yeah, and nick, from your perspective, you’ve taken a little bit different path to get to where you are getting Master of Arts in environmental based sciences.

And yeah, but environmental.

Studies actually on.

Environmental.

Studies, the.

Science interloper here.

Yeah, please tell that story.

Well, the. I mean, it’s almost a cliche that the story is that I was having a beer on New Year’s Eve with a friend and an M.D., Ph.D., program early like nine. And there was a there was a competition sponsored by an agency called the Defense Threat Reduction Agency, or Vitra, which one of the functions that they

perform as they kind of act as the CDC for the Defense Department. They also run a series of overseas labs, and they’re really interested in weird infections that, you know, military personnel and others get out and they’re also interested in biodefense.

So, they were running this competition for better metagenomics algorithms in 2013. I didn’t know what metagenomics was on New Year’s Eve 2012, but by kind of mid-January, my friend had convinced me to dive in headlong because I knew about software and contests, and he knew about genomics.

And so… really my background is more in thinking about scientific data and data at scale and software, and we approach the problem algorithmically built some cool early technology that we found really intellectually compelling and then put a little demo together that we thought folks would say like, Oh, the algorithms so accurate or oh, the algorithm so

fast. And it was a crummy demo like a really crummy, ugly experience. And we put it on Twitter as one is wanting to do. And folks said, oh, this is so easy to use. And that was kind of that was in maybe March or April of 2014.

And that was kind of the aha moment of we thought we’d built a really cool piece of really cool piece of computational biology software with some data structures and other very low-level details. And then we put a really crude web interface in front of it, and people said that’s really compelling and useful.

And I think at the time, it’s probably still too early. But at the time, you know, there were MySEQ’s landing and state public health laboratories and kind of more and more groups outside of a few of the core kind of early Pioneer Labs were starting to do microbiome.

And so, I think, you know, there was this real need to. Help more applied scientists or folks who aren’t kind of computational, we focused access and make sense of some of this data, and that was kind of the genesis of what became one codex and how we got into the space and obviously dry side perspective

and bias. But yeah, we were a bunch of data weenies, basically.

I like the science, the science for scientists, the data, the bioinformatics side of it. Can you talk a bit about creating a startup that was kind of for scientists that and now it’s been taken up by Invitae and is more public medical facing?

But the startup part of it was it just primarily like, oh, we’re putting it out there for the scientific community to access and use?

Yeah. Well, it’s a good question. So, we did a lot of that. I think if anyone in the audience is thinking about software startups, for scientists, it’s a very hard thing to sell because, you know, unfortunately. Well, I don’t know.

Scientists don’t really like paying for software as a general rule, and there’s a lot of, I guess, under accounted for labor and academic institutions that that can be used in lieu of paying for third party services and science and software in particular.

So, we didn’t really focus on selling to that academic scientific market. We really… our core business was and remains actually, at Invitae be focused on helping biopharma groups, folks doing live biotherapeutics development and otherwise interested in the role of interactions between microbiome and other life, by therapeutics or other therapeutics.

To more systematically understand who’s there in these samples, where the different bugs that are present, as well as what’s going on. So, so we always thought of ourselves as building tools to enable greater velocity of either therapeutic discovery or assay development.

And I think that in Invitae, actually, we’re really supporting both that as well as internally. We’re now obviously at a diagnostics company interested in the microbiome as a source of biomarkers for diagnostics. And the software is really, and data infrastructure is really about supporting that effort at scale and with a certain amount of velocity so that

it can be, you know, so hopefully we can get there and find something interesting and bring something into the world that improves then impacts patients’ lives.

Yeah, thank you. And Momo, your company, you’ve gotten into Nordstrom stores at Bloomingdales, you’re working very highly at the consumer facing interface. So, can you talk about creating a product that is so consumer focused?

I can. So, I do want to intrude with a little bit of an understanding of our company. So, our company recently renamed was renamed to Viome Life Sciences and everything that you can see on Viome dot com. It’s simply one application, just one application of our technology platform, and I am actually on the not on that part

of the company. I’m actually cleaning our Viome health sciences platform. And I want to mention this briefly because I’m really particularly excited about it. The systems biology platform we’ve created. It enables clinical research and large data collection from samples and data analyzes and data science and machine learning.

And this platform has been developed over the last eleven years, both prior at Los Alamos National Lab six years and here at Viome for five years. And the really exciting part about this platform is think of it as the App Store.

So, it’s like a health app store where we provide all the software and the hardware, and anyone can plug into this platform. It’s literally now open to the whole world. So, everything that I have at my disposal, anyone in the whole world can access that 100%.

And so, it’s an open platform where others can build whatever health application is of their interest, whether they want to build a diagnostic device for whatever favorite disease they have or a companion diagnostic device for any drug they’re interested in or look for therapeutic targets.

And so that’s really exciting to me. And then Viacom is just one of the applications we’re building, other applications in cancer diagnostics and vaccines and therapeutics and so on. So, let’s not talk about that one application, Viome dot com. So that is a direct-to-consumer wellness service where consumers provide their stool and blood and soon saliva samples as

well. They actually collect all these at home ship them for our clinical labs, we generate what I call chemistry data. They’re actually metatranscriptomic data, but I call them chemistry and then we overlay mathematical equations. On top of that, those chemistry data to generate personalized food and supplement recommendations for every customer.

And those supplements, they can go purchase them on their own, or they can actually purchase them via subscription from Viome directly. And so, this was basically one of the original ideas as one of the applications of the platform.

And so. Very quickly, we got to work on that, so five months after we started the company, we already offered the stool test and some initial recommendations. And at that time, the recommendations were actually made manually by a large team of people.

So, it was like a team of nutritionists and molecular physiologists and microbial physiologists and some naturopathic doctors. So, it’s really, they would get the data out of the lab, and they would interpret them. But after the initial few months, they actually started teaching all the all our A.I., all the algorithms that they were using for

this. And I started learning from all the data and from our clinical research. And so, about a year and a half later, all everything was replaced by automated algorithms. And then we added the blood test, and now we’re adding the saliva test.

So, we really want to understand it every kind of a chronic disease in sense of systems biology. I’m not sure if you had any specific questions about this.

No, I find it interesting. What I what I was trying to get out was the question of actually producing something that is usable by the consumers and so that the ability of your team, which is multifaceted to be able to interpret your scientific data to create that product, that then is something that, as Ivan asked

earlier, was a question to Chris Mason of, you know, are we not overselling the microbiome to people?

Yeah, I mean, we are just starting. We’re scratching the surface of the tip of the iceberg. So, we’re just starting, but you have to start somewhere. And as long as people don’t make health claims based on, you know, no trials, then that I think it’s OK to start and we are seeing some absolutely phenomenal improvements in some of

our customers and it’s going to get better and better because we’ve created a platform that self-learning. And it’s like a flywheel. And so, for example, one of the fundamental differences between Viome and, let’s say, Quest Laboratories, is that when Quest Laboratories performs 1,000,000th test on a patient, they provide no additional information than from the first test, meaning

they have not learned anything. They simply collect the sample, do the test and report the data. Whereas we use every single additional customer and all the data we get, we use it for machine learning so that every new customer benefits more.

And so, it’s really a self-learning flywheel. So and as we go, we’ll learn more. And right now, you know, I get a I get an email from a customer saying, you know, my psoriasis completely went away, and I’ve been trying to treat it for 40 years.

And they went to Japan, and they went to Bulgaria, and they drink the holy water, and they tried every pharmaceutical and nothing worked. And three months after the Viome diet, their psoriasis went away and they asked me, How the hell did you do this?

And I said, I don’t know. Well, we are not treating psoriasis. We don’t know how to treat psoriasis. But what we’re doing is we’re modulating the microbiome to produce fewer pro-inflammatory signals and to produce more anti-inflammatory signals and just so happens in you.

That was what was the cause of your psoriasis. And we succeeded. But it’s not like a pharmaceutical where you can target a very specific pathway and you can inhibit it, and that was the cause of disease. So, we’re still having to learn a lot and we are only really, we’ve already legally made huge progress in four indications

so far, but we’re going through more.

Great. And, Colleen, your company Pendulum is working in the medical therapeutics industry, but can you talk a bit about how interfacing with the medical community, interfacing with organizations that you need? How do you how do you how do you navigate all of the integrations that need to happen for your company?

Yeah, well, we’re not doing drug development in the way of pharmaceutical would and so we’re selling our products directly to consumers, and I think it’s super important when we’re talking about disease states that the health care community is behind you and you’re continuing to bring them along on the journey because people as much information is available from

Dr. Google. People still do also talk to their actual health care providers. And so, for us, you know, there’s a couple of really important things. The first is that the Mayo Clinic were our first investors and they’ve invested in us at every round.

And I think that that was sort of the beginnings, the foundation of the company and being really clinically and scientifically focused and driven. We have academic partners and clinical partners that we have trials that we’ve been running with, and I think COVID really, really caused us to lose a lot of money on that front.

However, I think it is really important to keep that front and center to Momo’s point. It’s not just about running a trial; it’s continuing to run trials. It’s showing that your product works in different settings and understanding more about where is there a microbiome opportunity and where is there not.

And I think that’s been really important. So, we have educational materials, clinical trial work, medical advisory boards, scientific advisory board, you know, and I always joke that those aren’t just pretty pictures on a website. We actually put all of our advisors to work so.

Chris Mason, who was on earlier, is one of our advisors. We have multiple collaborations together, including through his company, Onegevity. And so, I think those are it’s important to really stick to the science and the medicine so that you aren’t just putting out.

I think somebody wrote earlier shampoo with microbiome in it.

Yeah. Not just sharp shampoo with microbiome, it’s what microbiome, what aspects are you influencing its ecology here we’re talking about? But speaking of systems ecology, as a woman in science and a female CEO, you are. You are a rarity, and I would love it if you could speak to your experiences in in trying to secure funding and

to actually managing a company as a woman and there have been any specific challenges.

Well, I think it’s pretty well established that it’s hard to start a company no matter what. And securing fundraising is hard, I think, and managing teams and growing teams and setting a vision and figuring out when you need a pivot and when you shouldn’t pivot and kind of dig your heels.

And all of those are the challenges of being a founder. And I would say probably for me, the most important thing that I’ve experienced is having co-founders as really important, and I think I don’t know how anybody starts a company by themselves.

But having co-founders that are literally going through the same thing as you or being able to divvy up work or just having someone that you can. Say all the things you’re worried about are nervous about two very openly, it gets harder and harder as the company grows because, you know, there’s not that you don’t want to be

transparent, but there’s just certain fears that you should just keep to yourself. So, I think that having co-founders makes life much easier and much like anything else, just having partnerships and people and a good support network around you helps you be successful.

But I only have an end of one. I’ve never started another company, but I can say, like, it’s ******* hard to raise money. I don’t care who you are.

I think that is just a truism. Put it on a T-shirt and bumper stickers, though. So, we have some questions this half hour. I knew it was going to go by very quickly, but it is just zipping past.

We have some questions from our audience. For those of all of you who have transitioned to industry, McKenzie Lynes is asking How has that transition changed your perspective on science? So, Momo, if you want to start this one.

Well, I kind of had this perspective before I transitioned to industry, I really wanted to do something applied as something that can change people’s lives. So that has remained the same always. I did not, you know, I went to I went to an academic retirement party and the person had published 180 papers and it was

a big To-Do. And it was like, wow, this guy is amazing. He published 180 papers. And I asked, did this that any of these papers impact any humans on this planet in any positive way? And that was a difficult question to answer because they really didn’t.

And so, this is the kind of realization that drove me to exit that academic world where it’s publish proposals, publish proposals, published proposals, just exit that cycle and do something that actually changes people’s lives. And it’s true in industry, you can actually do that.

Yeah, quite true, Colleen.

Yeah, I totally agree, I think being able to point to a population of people and say it changes people’s lives is extremely rewarding and you come in every day. Your goal isn’t around publishing. Your goal is around. How many more people can I help?

And so, if that’s the kind of thing that motivates you, it’s very rewarding to be an industry. I would say the thing that most surprised me when I had my first job in industry coming out of academia because I didn’t work in between my education I just went straight through was that I feel like there was this

perception that if you’re a really good scientist, you’re in academia, you’re a professor. And if you’re like a, you know, second tier scientist or you’re OK, you’re an industry. And I would say that I at my first job, I just kind of walk through the doors thinking that I was going to be a hot shot and

I was definitely not a hot shot. And I think what I. My perspective changed that there are amazing scientists up and down, left and right and industry. And so, if you’re coming out of academia and you only know that one world and you’ve only seen your professors and their colleagues and what that life looks like, I encourage

people to go hang out with some people in industry. See if you can shadow sit in on a lab meeting because I think what you’ll find is that there’s amazing science with just a slightly different perspective that’s going on everywhere.

And I think that was that was important. I just learned it by accident.

Thank you for sharing that. And Nick, did your perspective change?

Well, I don’t I don’t know. I didn’t go through that transition, so yeah.

But you did transition to industries. I mean, you weren’t specifically working in industry.

Yes, I did transition to yes, I transition to microbiome. I mean, I guess I can say a tiny bit about that. But yeah. For me and for the team that we built and now actually the team at Invitae, I think, you know, the reason I got into this space was very much to pursue.

Well, I was in San Francisco, right? There’s a common trope about how there are a lot of brilliant minds being wasted on optimizing ad spend. And I think there’s some truth to that. And, you know, this was a compelling problem through which.

Better software, better data analysis, some of those skills that that I and the team that we built had could, you know, make a difference, whether that’s by accelerating certain therapeutics developments or whether that’s, you know, particular diagnostic opportunities that I think are still a few a little way down the line.

But that we’re actively working towards. And so, I think, you know, finding that was really meaningful for me and really meaningful for the team and kind of that industry transition was really motivated by knowing or having the intuition that that would be there, that kind of meaningful balance of something that was both intellectually engaging but

also had a had a deeper purpose than ads. Not that I worked on ads before or just for the record, but you know, could happen.

If you want more than just clicks, that’s good. And as we get down into the last minute or so, hear from each of you. I’d love to see if you have any words of wisdom for future generations of microbiome startup founders.

If there’s one thing that you could tell yourself before you started, what would you go back and tell yourself? Nick, if you want to start this.

Sure. Well, so I think what Colleen said is true, a lot of things, Colleen said, are true. So, I think it’s very hard to raise money. I think it’s very hard to do. I’m sort of a solo founder and that wasn’t that kind of happened by accident.

And some just like unfortunate context about return to medical school of my co-founder and things like this. I wouldn’t do it that way, like I would strongly recommend not doing it that way. I think having a partner or a couple partners as you get started is really important and really valuable, and I’m particularly stubborn, so I

like managed to get through it. I think being stubborn in general and like not taking no for an answer is an essential quality of a founder and a lot of ways because you’ll go through some valleys or troughs, for sure.

It’s just a question of how deep they are and how regular on the journey. So, I think all those things are true. I think getting great partners is really important. If you can, then if you can’t have those people as co-founders having them as your early team, it’s really important.

And then I guess the other thing I would say is. I think that people often. Think that despite the responsibility and burden of the startup resting on the founders’ shoulders, which it often does a particularly in relationships with investors, I think sometimes there’s an incredible community of folks who’ve built companies or done similarly entrepreneurial things that

I think are there for folks to reach out to and are happy to give back and kind of pay it forward. You know, so I would also say finding folks who’ve been in your shoes or the path that you hope to walk can be hugely helpful.

And, you know, speaking for myself, like if anyone’s doing anything and microbiome on the bio side, I’m always happy to chat and I think a lot of people are.

Momo, would you like to chime in here?

Yeah, I have a couple of actually suggestions. one is that to me, I think while thinking of, say, an academic position or any kind of a position where you have a job and you’re not actually a founder, well, that seems to be less risky.

And people say, 00, founding a company, a company is too risky. I would actually turn that around and say that it’s actually far riskier to have that cushy job because it’s going to prevent you from reaching your maximum potential.

It’s going to slow you down over time. And you’re basically you already know what you’re risking. You’re risking making big progress. You already are setting yourself on a path. Right? Whereas if you become an entrepreneur, you may have failures.

I mean, you guys saw Chris Mason had a failure early on and look at what he’s doing today, right? So, you may have failures. You may have these valleys where you may feel like you made a mistake, but as long as you keep learning and growing, you will eventually come out a winner.

So that to me is a is really the perception that I think is wrong among most people to think that it’s risky to do a startup. I think it’s the opposite. So that’s one thing. And the other thing that I want to mention is it’s the people, it’s the people who you co-found with.

It’s the people who you hire, it’s the partners that you work with. Nothing else matters or everything else to me is just, you know, patents, trade secrets, location, theme. All that stuff is just not important. If you have the right people, you will succeed.

It’s really that simple. And so, pick the right co-founders, the right employees, the right partners, and life is going to be just a blissful success.

You’ll be sitting pretty. And Colin, do you want to finish? Just finish us up here with some advice.

Wow. I really. They took all my ideas. Now I think it’s great advice. I mean, I didn’t get any advice when I started the company. So, it’s kind of like having kids. It’s better to not know what’s about to happen.

I think in addition to all of the awesome ideas here, even though we kind of all very clearly said it’s very hard to fundraise, I think it’s actually really important to try to pick investors that are that are going to be good for you and for the company.

And what that means is like, there’s a tendency to try to alter your pitch to be the thing that you think that investor wants to invest in. And the goal isn’t to get that dollar in the door. That is the immediate goal.

But the goal is to build a company that is going to create the kind of change that you’re envisioning when you start the company. And so, to the point that the moment is all about the people, it’s not just the people in your company, it’s also the investors that you surround yourself with.

And science is hard, and it takes a while to do things. And so having investors that are alongside you for that and aren’t going to pressure you to do things that aren’t really your vision of the company, I think is super important.

It’s hard. It’s a hard thing to do when you’re out trying to get a book to say and also be selective. But I do think it makes a difference to end up with strong investors that are aligned with you.

And the other thing I would say is that expect failure. Failure is just a part of the whole thing. Little failures every day. Larger failures company going under. All of these things are just part of growing and learning.

And if you’re not feeling you’re not really doing something interesting. And so, I think just trying to be not afraid of failure and embracing it, I think is important you’re being courageous if you’re starting a company and failure comes with that.

Yeah, I think scientists, people going through the scientific process are probably well versed in failure, so many experience experiments don’t go anywhere. Your methods don’t work. The protocols are wrong. You have to go back to the drawing board.

So hopefully, you know, this is something that many scientists, graduate students, postdocs are in the process of really getting good at right now to be able to take into their into the world with them. Thank you all of you for this wonderful conversation.

This has been great to get. Get your information. And if anybody in the chat giving comments has questions about specific companies, you can reach out to these individuals separately.

Great. Thank you. Thank you, everyone. I’m just echoing what Kiki said. We really appreciate that as a great panel and yeah, like, thank you for your insights. So, I’m going to go ahead and remove you from the stream.

So, thank you and goodbye. And then we’ll wrap up the event.

Oh, why hello there? Well, thank you guys for staying through all that. That was awesome. Nick, Colleen, Momo, I’ve known you guys for a long time. We worked together, possibly eaten burritos together. But to see you guys all in the panel is like amazing.

I’m very privileged to have you. Dr. Kiki is an awesome moderator. For those of you in the audience. Don’t know. Dr. Typekit runs a podcast called This Week in Science. That is super fun, and I was the guest on it once, and you all should watch it or listen to it.

And they talk about not just genomics. They talk about like space and like fungi that control ants and like that kind of stuff. And so big shout out to that big shout out to our sponsors once again. And the final thing we do at the end is I’m going to give away two more of these babies

and the winners are. McKenzie Lynes and Karl Sabby, you’re going to get an email at the end of this and you’re going to get your very own DNA socks, everybody else. Thank you so much. Follow us on Twitter.

I was about to say smash that subscribe button, but I forgot this is not a Minecraft play video. So, follow us on Twitter. We’re going to have more of these. Send us questions. You know, our goal is to connect you and help you guys do what you need to do.

So, with that, I guess I’ll just sort of stop talking and thank you for coming.

Thank you, everyone. Have a good evening.

100 Publications

 

 

Over 100 scientific papers have been published using Phase Genomics technology!

 

Since our founding in 2015, we have sought to bring transformative change to research, industry, and the clinic by building and providing cutting-edge genomic solutions to scientists all over the globe. Now, in 2021, we are happy to look back at the accomplishments made by those using our kits, services, and software.

 

Our team of researchers, computational scientists, and bioinformaticians have refined our ProxiMeta and Proximo Platforms (as well as many other products) to construct platinum genomes, master the microbiome, and expand our knowledge of the human genome and epigenomics. From potatoes to people, cassava to cannabis, bison to basenjis, our molecular tools and software have been used to drive genomic discoveries across many scientific fields. We encourage you to take a look at the fascinating collection of articles we have compiled here that explore more research using our technology.

 

Over the years, we have also helped break records and make headlines as researchers use our platforms to make breakthroughs in science.

 

A Question Hidden in the Platypus Genome: Are We the Weird Ones?

-The New York Times

Phase Genomics Releases Platform for Discovering New Viruses in Microbiome Samples

-BusinessWire

Precision Medicine Looks beyond DNA Sequences

-Genetic Engineering and Biotechnology News

 

We are grateful to all the researchers who have been working with us to accomplish these feats. Together, we can drive innovation and continue to make advances in genomic science. We will continue to work on ways to add applications and support current research, making it easier to get high-quality data and comprehensive reports.

 

Follow us on social media (Twitter, LinkedIn, YouTube) or subscribe to our quarterly newsletter (Phasebook) to receive updates on our technology and highlights from the latest in genomics.

Unlock the Virome with ProxiPhage

viruses moving through a net

 

Metagenomic studies are illuminating the diverse array of microbiomes that exist from the ocean floor to our gastrointestinal tracts. Understanding these microbial communities is essential to understanding modern health and the environment; however, outdated lab techniques are laborious, costly, and fail to create a complete picture of the microbiome. This article, posted by Ivan Liachko, describes how advancements in biotechnology are facilitating exciting discoveries with recent tools developed to capture phage and other mobile genetic element dynamics within microbiome samples.

Continue reading to discover how ProxiPhage, a recent addition to the ProxiMeta platform, is helping scientists answer questions relating to microbiome composition dynamics, prophage prevalence, frequency of transient infections, spread of antibiotic resistance, and more.

https://www.linkedin.com/pulse/unlocking-virome-proximity-guided-metagenomics-new-frontier-liachko/

 

 

Academia to Industry: What Students can Do to Prepare for Startup Career Paths

Five panelists speaking during online event

 

“Try not to be a sociopath” – Robert Hayes, PhD

A morsel of advice unanimously agreed upon by the panel of experts at the Spring Genome Startup Day event, good communication and empathy go a long way in startup environments. However, it takes more than a good attitude to flourish in this diverse and expanding industry. During our Spring Meetup, we assembled a panel of speakers to discuss how to succeed in a startup, to explore the range of startup career paths, and to provide advice on making the jump from academia to industry. 

 

The Bridge to Success

Initiating the fireside chat, CEO of Phase Genomics, Ivan Liachko, PhD, along with founder and CTO of Pacific Biosciences, Stephen Turner, PhD, also emphasized the importance of passion in the startup workforce. 

“Startups succeed because of the passion of the employees.” – Stephen Turner, PhD

However, Turner noted that startups must have more than ambition, and work tactically to “build the bridge” between their product and their consumer base. This notion was echoed in our panelist discussion. Lena Shaw, director of marketing at Navigating Cancer, cautioned against being caught in the “overanalysis paralysis” of technological development, and instead, focusing on improving client outcomes, which drive startups towards success. 

 

Foundation & Integration

Many entering startup companies look for positions outside of being a founder or CEO. During the event, fireside speakers and panelists had a lot to say about the wide range of roles in startup communities and how to prepare for them. While each role may vary depending on the company and its needs, there are universal traits that will facilitate better integration into startup working environments.

A common theme discussed was the importance of versatility. Gabriella Kiss, PhD shared her experience with the transition from working in a very specialized position as a doctoral student to the multiple roles she undertook when moving to a startup company. Moreover, just as important as versatility, is communicability. Being responsive and working well in close-knit environments is essential to performing well in these companies. Panelists described their work life as akin to family life, needing to collaborate to overcome differences and disagreements. 

 

Starting during a Pandemic

Despite the complications the COVID-19 pandemic imposed on the world, our speakers remarked that biotech startups are actually growing! Dr. Kiss noted that working with teams around the world became more economic and ecological as many adapted to online conferences instead of flying for meetings that could otherwise be done virtually. Furthermore, several panelists mentioned the growth they have experienced in their companies over the past year. Concluding the meetup, they were adamant about encouraging viewers to seek startup employment opportunities, assuring that startups are always looking for the right candidate to hire. 

 

View the event recording below for the full conversation and more insights into the world of biotech startups. 

 


Stay up to date with Genome Startup Day on Twitter and LinkedIn or watch previous events on the Genome Startup Day website.


 

Better together: long-range and long-read DNA sequencing methods, combined, reach record heights in microbiome discovery

Microbiome plate and Phase Genomics logo. Reads "Breaking records in microbiome discovery"

 

Click here for an updated blog post.

 

Since its debut, next-generation sequencing has not rested on its laurels. Improved sequencing platforms have reduced error and lengthened reads into the tens of thousands of bases. The debut of long-range sequencing methods that are based on proximity ligation (aka Hi-C) has brought a new order-of-magnitude into reach by linking DNA strands with their neighbors before sequencing.

 

This progress has birthed high-resolution metagenomics, the sequencing and assembly of genomes from environmental samples to study ecosystem dynamics. But metagenomic experiments often undersample microbial diversity, missing rare residents, overlooking closely related organisms (like bacterial strains), losing rich genetic data (like metabolite gene clusters), and ignoring host-viral or host-plasmid interactions.

 

A revolution within a revolution

 

New sequencing platforms and methods can reform metagenomics from within. Long-read platforms, such as the PacBio® Sequel® IIe system, now yield HiFi reads of up to 15,000 base pairs with error rates below 1%. In addition, Phase Genomics created ProxiMeta™ kits to generate proximity-ligated long-range sequencing libraries, which preserve associations between DNA strands originating in the same cell.

 

In a study posted May 4 to bioRxiv, a team — led by Dr. Timothy Smith and Dr. Derek Bickhart at the U.S. Department of Agriculture and Dr. Pavel Pevzner at the University of California, San Diego — employed both PacBio HiFi sequencing and ProxiMeta in a deep sequencing experiment to uncover record levels of microbial diversity from a fecal sample of a Katahdin lamb. Combined, PacBio HiFi sequencing and ProxiMeta eased assembly, recovered rare microbes, resolved hundreds of strains and haplotypes, and preserved hundreds of plasmid and viral interactions.

 

HiFi family trees

 

The team constructed SMRTbell® libraries to generate HiFi data, and ProxiMeta kits to generate long-range libraries. The two datasets, along with the metaFlye and ProxiMeta algorithms, allowed them to assemble contigs and create draft genomes without manual curation.

 

Researchers compared the breadth and depth of HiFi data-derived metagenome-assembled genomes, or MAGs, to control MAGs from assemblies of the same sample made using long, error-prone reads. HiFi data yielded more complete MAGs — 428 versus 335 — from more bacteria and archaea. HiFi data also generated more low-prevalence MAGs, capturing a larger slice of the community’s diversity by picking up more genomes from less common residents.

 

The HiFi MAGs also contained more than 1,400 complete and 350 partial sets of gene clusters for synthesizing metabolites such as proteasome inhibitors, which likely help some of these microbes colonize the gut. HiFi data picked up about 40% more of such clusters than control MAGs, illustrating just how much data is lost when long reads aren’t also highly accurate reads.

 

The team also used the HiFi MAGs to trace lineages within the community. They computationally resolved 220 MAGs into strain haplotypes, based largely on variations within single-copy genes. One MAG had 25 different haplotypes, which are likely strains of the same genus or species.

 

ProxiMeta’s long-range discoveries

 

The ProxiMeta-generated libraries added flesh to these MAG frames skeletons by unveiling additional rich biological information. Long-range sequencing linked nearly 300 HiFi-assembled plasmids to specific MAGs — revealing the species that hosted them. One plasmid, for example, was found in bacteria from 13 different genera. Long-range data also identified the first plasmids associated with two archaea, Methanobrevibacter and Methanosphaera.

 

Long-range sequencing illuminated the viral burden in this community. The HiFi library included nearly 400 viral contigs, more than half of which came from a single family of viruses that infect both bacteria and archaea. The team identified 424 unique viral-host interactions, including 60 between viruses and archaea, which is a more than 7-fold increase over controls.

 

What’s around the bend?

 

This study has lessons beyond one lamb’s gastrointestinal tract. It shows decisively that the highly accurate long reads generated by HiFi sequencing ideal partners for Hi-C-derived methods like ProxiMeta — together generating increasingly sophisticated metagenome assemblies for biologists to interrogate.

 

Applied to other environmental samples, this platform could illuminate the diversity and complexity of other microbial communities — from the bottom of the sea to mountain peaks, and within the stomach of every human being. It could probe pressing issues of our day, such as antibiotic resistance, soil health, or how microbes can break down pollutants. These endeavors will not just fuel the engines of scientific inquiry. Broader use of this method could generate new insights into pressing problems of our times, including antibiotic resistance.

New genome assembly method makes fruitful advances in genomic technology

 

A collaboration between Phase Genomics and Pacific Biosciences of California is bringing about the next generation of genome assembly technology. A newly published software tool, FALCON-Phase, combines genomic proximity ligation methods developed by Phase Genomics™, with the high accuracy, long-read sequencing data from PacBio®, enabling researchers to create haplotype-resolved genome sequences on a chromosomal scale, without having parental genome data. This method and its application to several animal genomes was published today in Nature Communications.

cow, zebra finch, and human hand arranged in a collage

Humans, as well as other animals, carry DNA sequence copies from both parents. These parental sequence “haplotypes” can carry millions of mutations unique to one of the parents and are often very relevant to diseases and other genetic traits. Until recently, accurately separating paternal and maternal mutations on the whole-genome scale required sequence information from the individual parents or extensive efforts that relied heavily on imputation from population studies. The new method employs the physical proximity information captured by proximity ligation (a technology also known as “Hi-C”) to separate maternal and paternal haplotype information from long-read genome assemblies. This development significantly increases the actionable information content coming out of genome sequencing studies.

 

 

“It’s an exciting time for genome assembly and PacBio HiFi sequencing continues to lead the way in this area with its powerful combination of read length and accuracy,” wrote Jonas Korlach, Chief Scientific Officer at Pacific Biosciences. “Phase Genomics Hi-C complements PacBio technology by extending our data into the ultra-long-range domain, enabling us to connect phase blocks and deliver chromosome-scale diploid assemblies without parental data. We are fortunate to have this excellent partnership with Phase Genomics, and we look forward to continuing to work together to create the highest quality reference genomes available.”

 

Assembling two fully-phased genomes in a single, streamlined process not only saves on the costs of research, but it also enables scientists to upgrade their genome assembly pipelines and obtain previously unobtainable information.

 

Dr. Erich Jarvis, professor at Rockefeller University and chair of the international Vertebrate Genomes Project, wrote, “Chromosome-scale haplotype phasing is critical for generating accurate genome assemblies and for understanding genomic variation within a species.” Furthermore, FALCON-Phase produces maternal and paternal haplotypes without family-trio data, so it can be applied to wild-caught samples or organisms lacking pedigree information. Jarvis notes, “In wild populations that many work with, parental samples are usually unavailable and therefore we need a method that can phase paternal and maternal sequences in the offspring individuals. With FALCON-Phase, we are able to use the Hi-C data that we have already generated for genome scaffolding and add a new dimension to every genome assembly, even retrospectively for previous projects. Our collaboration with Phase Genomics and PacBio has been extremely fruitful and the combination of the two technologies through FALCON-Phase will be highly beneficial to genomic sequencing efforts focused on conservation.”

 

FALCON-Phase is applicable to any diploid genome, including plants, animals, and fungi. It is available as free of charge open-source software (https://github.com/phasegenomics/FALCON-Phase) and Phase Genomics offers services that include the application of this method to varying genome projects. See the latest news and publications on this and other genome assembly methods at https://phasegenomics.com/resources-and-support/publications/.

 

For more information, email us at info@phasegenomics.com.