Category: Uncategorized

Phase Genomics Announces Appointment of David Shoultz as First Chief Business Officer

Posted on October 8, 2024 by Benjamin Mitchell - Uncategorized

SEATTLE – Phase Genomics, Inc., a leading innovator at the forefront of genomics technology development, today announced the appointment of David Shoultz, PhD, MBA as the company’s first Chief Business Officer. A strategic addition to the executive suite, Shoultz will drive growth as Phase Genomics accelerates market awareness and its work to amplify the impact of technological innovation at the frontiers of human health.

“David’s experience at leading organizations in diverse therapeutic areas and global public health is critical for Phase Genomics’ growth strategy,” said Ivan Liachko, PhD, founder and CEO of Phase Genomics. “He brings the right know-how at the right time to accelerate adoption for our suite of technologies that unlock and integrate new layers of scientific discovery. We’re excited to have David aboard as we strengthen our mission to make the world a better, healthier place.”

Shoultz’s experience includes helping launch the Institute for Protein Design (IPD) spin-out Monod Bio, where he served as co-founder and COO prior to joining Phase Genomics. In addition to his role at Monod Bio, he was previously a key member of the global health product development team at the Bill & Melinda Gates Foundation before directing the global drug development program at PATH, and has also held scientific leadership positions at Neoleukin Therapeutics and PPD (acquired by Thermo Fisher Scientific). Shoultz has raised more than $150 million in venture and non-dilutive capital to accelerate ground-breaking innovations to the front lines of health and medicine.

“Ivan and team built Phase Genomics on a relentless and infectious scientific curiosity. It’s one of the many reasons I am proud to join this team working at the frontiers of discovery. They’ve engineered incredible technological breakthroughs for nearly a decade, and there’s more on the way,” said David Shoultz, PhD, MBA, chief business officer at Phase Genomics. “Phase Genomics has endeavored not only to advance leading-edge genomic tools for research, but to prove out their potential for real-world impact. Together, we’re meeting an enormous opportunity beyond the bench to alleviate the most tremendous needs across diverse therapeutic areas, including oncology and infectious disease.”

In conjunction with his other professional roles, Shoultz currently holds an affiliate professorship in the University of Washington’s Department of Epidemiology and has served as a translational advisor within the University’s IPD. He has been an advisor to Phase Genomics since January 2024.

Shoultz will be attending the BIO Investor Forum this October 15-16, 2024, in San Francisco. Learn more by following Phase Genomics on X and LinkedIn for the latest news and information.

Phase Genomics’ Technology Powers New Anti-Microbiota Vaccine with the Potential to Ease Global Environmental Impacts of Salmon Farming

Posted on July 23, 2024 by Benjamin Mitchell - Uncategorized

Salmon with vaccine and salmon lice swimming away

Data shows proprietary technology enables lower cost and higher efficacy through new induced-dysbiosis vaccine targeting a parasite’s microbiome

The salmon aquaculture industry has – to put it mildly – a lousy problem.

Sea lice have been sucking salmon dry at facilities across Europe and the Americas at a rate of more than 70 times their wild cousins¹, costing the industry a billion dollars annually and wreaking havoc on the natural environment. But researchers at the Universidad de Concepción in Chile recently developed a method to bite back through what could be the world’s first induced-dysbiosis vaccine. A team led by Phase Genomics’ longtime collaborator Dr. Cristian Gallardo Escárate spent the last half-decade creating a vaccine that rids salmon of their lice oppressors by knocking out a key component of the parasite’s microbiome.

The new, less expensive and more effective vaccine could produce major economic and environmental benefits. Farmed Atlantic salmon are Chile’s second largest export after copper. In 2021, salmon shipped out of the country were valued at almost $5 billion, according to the USDA. Yet infestations by the sea louse, Caligus rogercresseyi, in salmon aquaculture facilities dampen productivity, spread disease, threaten native fish and reduce profits. Like all sea lice, Caligus are crustaceans, not insects. The parasites attach themselves to their unfortunate fish hosts, feeding on blood and mucus. Lice keep salmon from growing and building muscle. They can also transmit pathogens, including an infectious viral anemia that can spread to native fish. Chilean salmon farms spend hundreds of millions of dollars trying to beat back C. rogercresseyi infestations with increasingly ineffective treatments.

The breakthrough from Gallardo Escárate’s lab at Chile’s Interdisciplinary Center for Aquaculture Research, which is nearing commercialization now, could become the first commercial example of a vaccine against a target’s microbiome. And Phase Genomics’ platform for metagenomics unlocked the new dimension of microbiome biology to drive the keystone discovery in salmon sea louse hologenomics.

Slashing costs and scaling back environmental impact with proximity ligation

Phase Genomics used its proximity ligation metagenomics technology to assemble and annotate the genomes of the entire sea louse, including the myriad microbes living within the parasite. Dr. Gallardo Escárate and his team combed through the never-before-seen data delivered by Phase Genomics to latch onto a key discovery: They realized that one bacterium was providing its louse host with a key metabolite, in this case iron, that the louse could not acquire on its own. The team’s resulting vaccine directly targets that microbe, creating a dysbiosis within the sea louse’s microbiota to turn off the louse’s metabolite tap, killing the pest in the process while saving the salmon.

Field tests show that salmon administered the anti-microbiota vaccine were essentially free of sea lice. If widely applied, Chile’s salmon aquaculture industry may find itself with extra biomass to export, fewer sea lice to cross-contaminate the natural environment, and more money in the bank. The initial findings, detailed recently in The Economist, show that vaccinated salmon are 90-95% louse free and more effective than fish managed using conventional antiparasitics. The new method also lowers the environmental impact from salmon farming, which accounts for 70% of all salmon consumed².

Cover image of an issue of The Economist with an image of a globe.

Image of an article from The Economist with an image of salmon

Phase Genomics’ proximity ligation unlocks anti-microbiota pest control from fish to farm for sustainable

Salmon farms in Canada, Great Britain and Scandinavia also suffer from sea lice, but a different species called Lepeophtheirus salmonis. Dr. Gallardo Escárate cites similar findings around common bacteria core among Chilean sea lice ectoparasites which he believes could present a common vulnerability to the current immune dysbiosis vaccine across species.

This is not only the first time metagenomic data have been used to create a vaccine against the microbiome of a target, Dr. Gallardo Escárate also believes this proximity ligation approach could serve as a template for the development of vaccines that protect against other parasitic ne’er-do-wells, whether they’re nibbling away at fish in the sea or four-legged farm animals on land.

“Without this detailed knowledge of this parasite and its microbiome, this vaccine would not exist – and we would not have a blueprint to look for this same phenomenon in other species,” says Phase Genomics founder and CEO Ivan Liachko. “This study nicely demonstrates why we need next-generation metagenomics: It has the power not just to solve problems in one or two economically important industries, but to reveal the patterns and leads that will transform dozens of industries. The days of blunt instruments are over. We now can target with surgical precision.”

Dr. Gallardo Escárate is currently conducting the largest study to date of the vaccine in one million salmon in the waters off of Chile.

¹https://www.captainjacksalaska.com/seafood/pc/catalog/salmon_diseases.pdf

²https://www.worldwildlife.org/industries/farmed-salmon

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

Posted on March 5, 2024 by Benjamin Mitchell - Uncategorized

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

A Year in Review: 2023

Posted on December 29, 2023 by Benjamin Mitchell - Uncategorized

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.

Metagenomics Innovation of the Year

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!

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

Posted on August 7, 2023 by Benjamin Mitchell - Uncategorized

$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.

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.

A Year in Review: 2022

Posted on January 19, 2023 by Benjamin Mitchell - Uncategorized

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

Tech-Boosted Genome Assembly Helps Resolve Closely Related Microbes in Metagenomic Sample (Genomeweb, Jan. 2022)
Phase Genomics Advances Precision Oncology with OncoTerra™ a New Ultra-Long-Range Sequencing Powered Platform (BusinessWire, Jan. 2022)
Biotech Leader, Kyiv Native Rallies Support For Ukraine (Bioprocess Online, March 2022)
With New Funding, Phase Genomics Seeks to Eliminate One of Biology’s Biggest Blind Spots (BusinessWire, June 2022)
Phase Genomics Wins $5.5M in NIH, Gates Foundation Grants for Therapeutic Phage Discovery (Genomeweb, June 2022)
Gates Foundation funds biotech company cataloging the viruses that infect bacteria (Geekwire, June 2022)

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!

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

Posted on November 14, 2022 by Benjamin Mitchell - Uncategorized

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.

Funding the Future of Cancer Research

Posted on April 20, 2022 by Benjamin Mitchell - Uncategorized

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 30^th, 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

Posted on April 1, 2022 by Benjamin Mitchell - Uncategorized

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

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

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

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.

A Year in Review: 2021

Posted on January 10, 2022 by Benjamin Mitchell - Uncategorized

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

“Phase Genomics to Develop Commercial Platform for the Discovery of New Viruses with $1.7 Million Grant” – Business Wire

Publications

In the News

“A Question Hidden in the Platypus Genome: Are We the Weird Ones?” – The New York Times
“Genomes go platinum” – Nature Portfolio
“One size doesn’t fit all” – Puget Sound Business Journal
“New “Genomic Microscope” for the Microbiome Discovers Carbon Dioxide-Eating Microbes Living in Superheated Seafloor” – ZME Science
“Phase Genomics Revs up Product Development for Hi-C Assay Applications with Eyes on Cytogenomics” – GenomeWeb

Webinars

Next Generation Cytogenomics for Reproductive Genetics and Oncology

Genome Startup Day

January Event – Accelerate, Incubate, Neither or Both?
May Event – Beyond CEO: Exploring the Range of Rewarding Startup Career Paths
October Event – More than a Gut Check: Behind-the-Scenes with Startup Leaders Breaking New Ground in the Microbiome Industry

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!

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

Phase Genomics Transformative Genome Phasing Tool (FALCON-Phase) Now Compatible with Nanopore Sequencing

Posted on October 28, 2019 by admin - Uncategorized

Nanopore and Hi-C produce a new fully-phased, chromosome-scale genome for the red raspberry.

On October 22, scientists at KeyGene revealed the first fully-phased, chromosome-scale reference genome for the red raspberry, sequenced with Oxford Nanopore long-read technology and scaffolded and phased into full chromosomes using Phase Genomics’ Proximo™ Hi-C method.

Assembling complex plant genomes used to be considered nearly impossible as they can be extremely large, polypoid, and contain highly repetitive regions. Long-read sequencing generates genomic data spanning very long regions, but still needs to be scaffolded, or “put together” into chromosomes. Proximo Hi-C not only helps guide the assembly to produce chromosome-level scaffolds but can also tell which sequences and mutations come from the maternal and paternal chromosome copies (this is called phasing). Our phasing method, FALCON-Phase was originally released in 2018 and was used in conjunction with the Proximo pipeline to generate this “platinum level” raspberry genome.

Read more about the assembly and future directions for the project here.

Q&A with Co-Author Dr. Nora Besansky about Malaria, Mosquitoes, Insecticides and Adaptations!

Posted on April 25, 2019 by admin - Uncategorized

New Genome Published for Malaria Vector Mosquito, An. funestus.

Plasmodium parasites—the microbes that cause malaria—are right at home in the tropics. After all, tropical regions harbor the two animals that the malaria parasites need to complete their complex lifecycle: female Anopheles mosquitoes and human beings. And in 2017 alone, Plasmodiumracked up 219 million cases of malaria, with 435,000 deaths…

Read the full article in Genes to Genomes!

By generating a high-quality genome assembly for one of these mosquitos, researchers in the future will be able to reveal genomic clues as to why An. funestus is able to be a key vector for malaria. Here is our the Q&A with Dr. Nora Besansky, a leading author behind the new genome assembly for malaria vector mosquito, An. funestus.

Why is it important to understand mosquito genetics in malaria research?

Dr. Besansky: Malaria parasites are not spread directly between humans, unlike cold or flu viruses. Malaria mosquitoes — the subset of all mosquitoes that spread the disease — are essential for malaria transmission. Mosquitoes must bite humans to spread the disease, but they don’t operate like dirty syringes. Malaria parasites enter the mosquito when it bites an infected human. The parasite then has to complete a long (at least 10-day) and exquisitely complex developmental process inside the mosquito before that mosquito can infect another human through its bite. The propensity of a mosquito to bite humans, and the ability of the malaria parasite to develop successfully inside of the mosquito depends on mosquito and parasite genetics. Mechanistic understanding of mosquito genetics provides novel opportunities for us to control disease transmission by mosquitoes, without harming the environment or other organisms.

How does access to health care affect treatment for malaria?

Dr. Besansky: Malaria is actually a curable disease — if humans are infected with malaria parasites that are susceptible to the current drugs, and if the infected humans have access to those drugs and to health care. But malaria is a disease of poverty. Health care is not often accessible or affordable, and malaria parasites are rapidly becoming resistant to anti-parasite drugs. Since these drugs have only a short-term effect in the human body, they are impractical for control of malaria in high-transmission parts of the world, even in the absence of parasite resistance, due to the economic burden and the lack of infrastructure for drug distribution.

How does the rise of insecticide use affect the spread of malaria?

Dr. Besansky: In the absence of an effective malaria vaccine, broad-spectrum insecticides against malaria mosquitoes are the mainstay of malaria control. But like malaria parasites, the mosquitoes are also becoming resistant to the insecticides that have been approved for use inside homes and on bed nets, particularly in the face of massively scaled-up insecticide-use campaigns to control malaria. Resistance not only means that mosquitoes can survive exposure to the insecticide; resistance can also be behavioral. For example, mosquitoes that normally enter houses to bite at night, when people are sleeping under bed nets, and rest on indoor walls may change their behavior to daytime biting and outdoor resting — making it much more difficult to specifically target those mosquitoes. Genetic research offers the opportunity to understand in detail aspects of mosquito behavior and physiology that are essential to the mosquito life cycle or to the parasite developmental process inside the mosquito, revealing new and specific ways to intervene and protect human health.

**Why is it important to have a chromosome-scale genome assembly for Anopheles funestus?**

Dr. Besansky: Human malaria is prevalent in many tropical regions across the globe. But Africa suffers disproportionately. About 90 percent of malaria cases and malaria deaths occur in tropical Africa south of the Sahara. This is mainly due to the dominance of two highly efficient mosquito vectors of human malaria that occur throughout that region: Anopheles gambiae and Anopheles funestus. Owing to its acknowledged importance in malaria transmission, An. gambiae was the first insect, after the fruit fly Drosophila melanogaster, to have its genome fully sequenced and assembled. Sequencing and assembly of other anopheline malaria vectors has lagged, but in 2015, an additional 16 Anopheles reference genomes were made available, among these An. funestus. However, limitations of the sequencing technologies applied at that time meant that these reference genomes were not chromosome-scale assemblies. Just as driving from New York to Los Angeles is facilitated by a road map, genetic research also is more powerful, efficient and accurate if the 260 million puzzle pieces of nucleotides in the nuclear genome are properly ordered and oriented.

**Does heterozygosity or haplotype diversity affect genome assembly methods for the Anopheles species?**

Dr. Besansky: A major international consortium, modeled after the 1,000 human genomes consortium, published its findings based on 765 An. gambiae mosquitoes sampled from natural populations. A major conclusion was that, on average, there is a polymorphic site every other nucleotide in An. gambiae, emphasizing the almost unprecedented heterozygosity of this species. This same consortium has begun work on An. funestus, a species expected to be equally diverse. Such nucleotide diversity is well-known to pose difficulties for chromosome-scale assemblies based on traditional sequencing technologies.

What are chromosomal inversions? Do they affect the spread of malaria?

Dr. Besansky: Chromosomal inversions are reversals in gene order that occur when a linear chromosome breaks in two places, and the intervening segment rotates 180 degrees before rejoining the other two pieces. They affect the spread of malaria, indirectly if not directly, because they typically contain hundreds or thousands of genes involved in climatic or local adaptation, allowing their mosquito carriers to fully exploit heterogeneous and otherwise challenging environments. Due to their modification of recombination rates along the chromosome, undetected inversions can mislead genome-wide association studies and other genetic studies. Chromosome-scale assemblies make it possible to localize inversions in the genome.

Hi-C Technology Links Antimicrobial Resistance Genes to the Microbiome

Posted on December 4, 2018 by admin - Hi-C, Metagenomics, ProxiMeta, Uncategorized

Antibiotic resistance is a rapidly growing global health threat as bacteria share and spread resistance genes via plasmids and other mobile genetic elements. Several teams of researchers applied a new method to understand which microorganisms house genes for antibiotic resistance within complex microbiome communities.
Read the paper, Linking the Resistome and Plasmidome to the Microbiome.

ANTIMICROBIAL RESISTANCE ON THE RISE

According to the World Health Organization, antimicrobial resistance (AMR) in microbial pathogens is expected to take 10 million lives by 2050 if there are no new pharmaceutical or technological advancements dedicated to combating this pressing problem. For almost a century, medicine has made remarkable impact on human life by using antibiotics to treat infections, but this has led to a very concerning overuse problem, stoking an arms race between antibiotics and the pathogens they target. The CDC points out that at least 30% of antibiotic prescriptions are unnecessary and there is a massive contribution to antibiotic overuse in the food and agriculture industry where each year 130,000 tons of antibiotics are given to food animal livestock. Both of these problems correlate with the rise of AMR.

Though there are naturally occurring antibiotic-resistant bacteria, there are two mechanisms by which bacteria can acquire antimicrobial resistance genes (ARGs) and become resistant: 1) through spontaneous genetic mutations and/or 2) by acquiring genetic material from other microbes via plasmids, viruses, or other means of horizontal gene transfer. Due to the evolutionary pressure exerted on microbes by antibiotic overuse, pathogens resistant to these antibiotics within our body, hospitals, and the environment become reservoirs of transmittable AMR genes that can rapidly spread and accumulate within a single microbe contributing to the emergence of multidrug-resistant microbes commonly known as superbugs.

PROXIMITY-LIGATION (HI-C) LINKS ARG AND PLASMIDS TO THEIR HOSTS

One of the biggest obstacles faced by scientists when studying AMR is the inability to determine which microbes are carrying and spreading specific ARGs. Because these genes often travel on mobile elements, they can move dynamically between different species and can therefore be found in numerous organisms without one clear parental host. When attempting to sequence the DNA of a mixed microbial sample, all the DNA is purified from all the cells at the same time and the host-plasmid connection is severed, making it nearly impossible to determine where each mobile element came from or if they were shared among several species. In this newly published paper, researchers highlight a novel method for linking ARGs and other mobile genetic elements to their hosts directly from microbiome samples using the latest version of the proximity-ligation (Hi-C) data analysis tool, ProxiMeta Hi-C.

Phase Genomics CEO, Dr. Ivan Liachko, describes how our Hi-C platform solves one of microbiologists’ greatest problems pertaining to the linking of plasmids with their hosts.

Hi-C utilizes in vivo proximity-ligation which can assemble complete genomes down to the strain-level directly from mixed-population samples as well as physically links plasmids/ARGs to their host. This method is particularly useful for researchers studying the “dark-matter” of the microbiome because the method does not require culturing nor a priori information about a sample.

USING HI-C TO TRACK ARGs IN THE MICROBIOME

Lead author Thibault Stalder from the University of Idaho used the ProxiMeta Hi-C kit on a complex microbiome wastewater community, a suspected AMR reservoir, to learn more about which bacteria carry ARGs. After the Hi-C library was sequenced, Phase Genomics used the data to inform contig clustering of hundreds of genomes, most of which are novel, with our cloud-based software – ProxiMeta. Using the genome clusters found by ProxiMeta, the Hi-C linkages of each ARG-, plasmid-, and integron-bearing contigs to each genome were measured to determine which species physically hosted the relevant mobile elements.

ProxiMeta was able to cluster contigs into >1000 genome clusters and search for over 30 groups of ARGs, plasmids, and integrons which speed up the adaptive process of newly integrated ARGs (Figure 1, circle plot). For each of these genes, we inferred hosts (Figure 2). Moreover, these organisms generally belonged to families known to host each known gene (marked with an “X” in Figure 2), supporting the accuracy of the analysis. In the future, this information will allow us to track the spread of AMR in complex communities consisting of many diverse organisms.

Microbiome Antibiotic Resistance Genes and Plasmids

Figure 1: Hi-C linkage between ARGs, plasmid markers, and integrons among clusters belonging to Alpha, Beta, Gamma and Delta Proteobacteria.

Over 200 genome clusters had strong Hi-C links to ARGs, of which 12 had high-quality assemblies. These resultant genomes include both gram positive and gram-negative bacteria and most belonged to species that were previously unsequenced. ARGs were mostly linked to genome clusters belonging to the Gammaproteobacteria, Betaproteobacteria and Bacteroidetes (Figure 2, below).

Microbiome Antibiotic Resistance Genes AMR and Plasmids

Figure 2: Normalized Hi-C links between ARGs, plasmids, and families of bacteria.

FUTURE DIRECTIONS

This method can be useful for researchers not only studying the microbiome, but the virome as well. Phages, or viruses, also distribute genetic information amongst bacteria to influence host biology, much like plasmids. Several previous studies showed that in vivo proximity-ligation can be used to link phages with their hosts directly from mixed complex samples, much like was done with plasmids and AMR genes in this study. This information could be crucial to labs and companies that are now engineering phages that could replace the widespread use of antibiotics and combat AMR.

This year, antibiotic resistant bugs have infected more than 2 million people globally; 23,000 of those individuals will die because of our inability to fight these superbugs. By using ProxiMeta Hi-C to better understand the genomics of microbial communities suspected to be AMR reservoirs, researchers can identify ARG carriers down to the strain-level and quantify how prevalent these genes are. With further exploration, this tool could one day offer a new solution to limit the spread of these genes and reverse the trend of increasing antibiotic resistance and save lives.

BRING A HI-C KIT INTO YOUR LAB TODAY

Phase Genomics offers a wide variety of proximity-ligation products and services including Hi-C preparation kits and a range of different cloud-based bioinformatic analysis platforms. Power your microbiome research with ProxiMeta Hi-C and our easy Hi-C kits; assemble hundreds of complete genomes for novel, unculturable microbes, and associate plasmids with hosts directly from raw microbiome samples using ProxiMeta Hi-C.

Earth’s Wine Cellar: Digging into the Microbiome of Vineyards

Posted on September 6, 2018 by admin - Hi-C, Metagenomics, ProxiMeta, Uncategorized

Phase Genomics partnered with Browne Family Vineyards to begin to understand, the microbiome makeup of soils within different vineyards across the state of Washington. The findings were unveiled at the Pacific Science Center’s “STEM: Science Uncorked” winetasting event.

There are many different factors that contribute to soil composition, such as parent material, topography, climate, geological time, and the thousands of different and undiscovered microbes living in the soil—the least understood factor. In April of 2018, Browne Family Vineyards staff visited five of their vineyards, filled a bag with soil from each site, and sent it to Phase Genomics to analyze the microbiome in each of the soil samples.

SYMBIOSIS BETWEEN PLANTS AND MICROBES

Plants rely heavily on their microbiome to live, grow, and protect themselves from pathogens. One example of this symbiotic relationship is that plants release chemicals into the soil in order to attract microbes. These microbes bring nutrients such as nitrogen, iron, potassium, and phosphorus to the plants in exchange for sugar, which the microbes require to survive. Microbes also play an important role in nitrogen fixation, organic decay, and biofilm production to protect the plant roots from drought. It is evident that this symbiotic relationship between microbes and plants is critical to the health and survival of both, but further research into this complex community is inhibited by two main problems: It is impossible to isolate microbes in such a complex mix and most of the microbes have never been discovered before.

THE DARK MATTER OF THE MICROBIOME

Microbes live in communities where they rely on each other. This makes it difficult to isolate or culture (i.e. grow) microbes without killing them or altering their genetic makeup. Moreover, there can be millions of microbes living in a single teaspoon of soil, making these samples extremely complex environments. This causes most of the microbial world to be unknown, sometimes referred to as the “Dark Matter of the Microbiome”.

The most effective way to identify the microbes in the community is to look at the genetic makeup of the microbiome to try to classify microbial genomes present. Standard practices include sequencing of 16S (a hypervariable genomic region) and shotgun sequencing. By combining these standard practices with Hi-C, researchers are now able to fully reconstruct genomes from a mix because Hi-C captures the DNA within each microbe to exploit key genetic features unique to each individual in the community. The Phase Genomics Hi-C kit and software, ProxiMeta^TM, uses this information to capture even novel genomes straight from the sample without culturing—illuminating the dark matter of the microbiome.

THE PROCEDURE

Figure 1: Shotgun Sequencing Procedure and Difficulties

Once the soil samples were collected from the five vineyards, Phase Genomics produced shotgun libraries to obtain DNA from all of the microbes in each sample (Figure 1)—essentially taking the soil sample, breaking open all of the microbial cells then purifying the DNA (1.A). Since DNA is fragile, most of it gets broken into smaller pieces during this process, leaving a mix of many DNA fragments from all of the microbes that were present in the original soil sample. The fragmented DNA is then sequenced and the “sequence reads” are uploaded into a database of known microbial genomes (1.B). This database then searches for matches or “hits” to see if the reads are similar to anything in the database (1.C).

A problem with relying on shotgun data is that it’s unclear which DNA fragments belong to which microbe, thus relying heavily on computational techniques and the accuracy of the reference database for classification. This results in little improvement or clarity on the makeup of the sample, again, leaving the microbiome in the dark. Though shotgun sequencing only provides a glimpse into the microbial community, this data allows scientists to differentiate the taxonomy (phyla, genera, species) of the microorganisms living in the soil.

THE RESULTS

Shotgun sequencing identified over 10,000 different species from each of the vineyard soil samples; however, it is impossible to know if this is the true number of species because only ~ 20% of the reads matched the database, indicating ~80% was either incomplete or undiscovered (see table below).

Table 1: Vineyard Read Classification
Vineyard	Total Reads	Percent of Reads Classified	Number of Organisms Found	Percent of Unknown Organisms
Canyon	19,001,222	15.95%	10,726	73.32%
Canoe Ridge	21,214,190	17.66%	11,721	55.55%
Waterbrook	19,469,954	19.6%	10,782	50.58%
Skyfall	63,850,810	16.17%	15,101	80.08%
Willow Crest	43,941,026	17.13%	13,914	71.84%

Moreover, of assigned reads, >50% did not match to a genus or species—hinting that many of the organisms found are novel. Without digging too deep into the microbiome analysis, it is evident that the microbial makeup is different for each of the samples. Varying levels of reads from each vineyard were able to be classified (Table 1), and among the classified reads, the vineyards have 3-4 microbes that vary in abundance in common. These microbes, such as Proteobacteria, Rhizobacteria, and Actinobacteria, generally, are very common in soil.

Proteobacteria

There are obvious differences in the biodiversity of the soil samples both in number of species and relative abundance. For example, Canoe Ridge and Waterbrook samples were >20%, Delftia, while the microbes in the other vineyards were more evenly distributed, with abundance closer to 1-5%. Interestingly, Delftia, a rod-shaped bacterium, has the ability to break down toxic chemicals and to produce gold.

Actinobacteria

There are two main components that influence microbe classification in these samples: the desired taxonomy level, and the statistical threshold, or minimum number of reads, set to define it. Much like zooming in and out, the most “zoomed out” analysis is achieved by a stringent threshold and will reveal phylum, while the most “zoomed in” analysis is achieved by a more lenient threshold and will reveal genus and species

If the data is “zoomed in” further, about 37% of the microbes in each community can be identified by genus. On average, 63% of the communities do not match to a genus at all, hinting that these microbes may have never been sequenced. The most abundant microbe genera present in these samples are Bradyrhizobium, Streptomyces, and Nocardiodes.

As discussed earlier, this data highlights the issues that are present with shotgun data and the corresponding analysis: there is still far too much that is unknown. In order to better understand these samples, we also performed Hi-C on two of the samples which will be discussed in further detail in the next section.

HI-C AND FINDING NOVEL GENOMES

One thing all these soil samples have in common is that they are composed of numerous novel species. To obtain more information on the microbes present in these samples, and solve the issue discussed earlier surrounding shotgun data, Hi-C was performed on two of the soil samples, Skyfall and Willow Crest. Essentially, Hi-C assigns DNA fragments from shotgun sequencing to the correct species by connecting DNA while the cells are still intact.

Hi-C enables clustering of shotgun assemblies and subsequently yields complete genomes from a microbiome, even if the genome has never been sequenced before. With complete microbe genomes, it becomes easier to classify organisms down to the strain-level—a step even further than species. By having the genome, we can essentially read a microorganism’s blueprint and learn more about its genes, evolution, and even function once the genome is annotated.

For example, preliminary data from the Willow Crest soil sample yielded 400 different genome clusters. When compared to known bacterial genomes in the RefSeq database, which aggregates all published microbial genomic data, over half of the extracted genomes are unable to be identified at a genus level and thus likely represent newly discovered bacterial organisms.

SCIENCE UNCORKED

When the microbiome data from the vineyards were presented to the public at the Pacific Science Center, two questions consistently arose: How does this influence wine taste, and how can growers select for a healthy microbiome? These very forward-thinking questions unfortunately cannot be answered—yet.

Scientists do know that soil plays a big role in plant health, and this could in part be due to the plants’ symbiotic relationship with microbes, as discussed earlier. It has also been shown that biodiversity can benefit plants because of the diverse functions individual microbes have, i.e. with more microbes, there are more potential functions being served versus 1 microbe serving one function. However, nailing down answers to these questions will take a lot of research. With emerging technologies, like Hi-C, the answers have become much more obtainable.

Though the term “microbiome” may not be household vocabulary, many of the attendees were very aware about the role that microbes play in human health, and how they influence the world around us. It goes to show that the rapid developments in the microbiome field are reaching beyond just research and becoming more tangible for the general public. Relevant stories—like looking into the microbiome of vineyards— are helping them understand the intricate concept of microbial life.

Learn more about ProxiMeta Hi-C and the microbiome by visiting our website www.phasegenomics.com and connect with us on twitter by following @PhaseGenomics