Tag: blog

A Year in Review: 2024

image of microscope and dna with Phase Genomics logo

 

Phase Genomics continues to pioneer genomic innovation, driving advancements in human health and life science research over another impactful year. Our efforts range from developing novel tools for detecting chromosomal abnormalities to managing the world’s most extensive phage-host interaction atlas, thereby accelerating genomic research and promoting a healthier future.

Our ultra-long-range sequencing technology is fostering advancements across a wide array of research applications, both at Phase Genomics and in laboratories worldwide. Utilizing our microbial platform, we are driving transformative discovery in metagenomics and ecology while making bounds in human health with cutting-edge approaches to antimicrobial research and oncology.

Thank you to our supporters, collaborators, and clients for their contributions to making this an outstanding year. Here are some key highlights from 2024.

 

Insights in oncology

This year, our cytogenetic platform uncovered novel, clinically-relevant chromosomal aberrations critical for assessing patient care in oncology. Genomic Proximity Mapping™ (GPM) is an upgraded approach to cytogenetic analysis – meeting and  surpassing current risk stratification assessments. Over the summer, researchers at Fred Hutchinson Cancer Center and University of Washington Medical Center published research that used GPM to analyze 48 patient samples, identifying known and novel chromosomal aberrations. Read the MedRxiv preprint to discover the expanding possibilities in leukemia research here » image of DNA

 

Cow burps, super bugs, and our enemy’s enemy–phages

We are actively developing solutions to address the growing threat of antimicrobial resistance and in the same stroke, advancing environmental health efforts with lysin discovery. By leveraging metagenomic data and AI, scientists can harness the evolutionary power of bacteriophages to target and eliminate harmful microbial pathogens with precision. Discover how we are turning the tables using our antimicrobial discovery platform with support from the Bill & Melinda Gates Foundation in our blog here »

 

A novel approach to vaccination

Phase Genomics’ metagenomic deconvolution technology helped crack the code on a potential new vaccine for farmed salmon to defend against sea lice by targeting the parasite’s microbiome. Published in The Economist, researcher Cristian Gallardo Escárate shares results that led to the creation of the groundbreaking invention that could ease global environmental impacts of salmon farming. More here » image of a salmon

Diving into the data 

Two new data analysis tools were made available to ProxiMeta and CytoTerra platform users this year: ProxiMeta™ Explorer and CytoTerra® Curator.  

ProxiMeta™ Explorer is an interactive, cloud-based genome-resolved metagenomic analysis platform for data visualization and exploration. The platform provides fully customizable analyses and reports for tracking genomes across time, conditions, groups, and more with a click of a button. 

CytoTerra® Curator enables users to effortlessly review, revise, and generate reports from cytogenetic data – no prior bioinformatics experience required. From curating calls to constructing circos plots, Curator provides fast, accurate insights for human genomics and oncology research.

 

Tune in to this year’s podcasts

Listen to Phase Genomics CEO, Ivan Liachko, discuss the breadth of applications supported by Phase Genomics’ ultra-long-range sequencing technology in these podcast episodes. Discover the story behind commercializing and implementing biotech innovations and get a glimpse at where this technology is taking us. 

 

Looking Forward

In 2025, we aim to elevate our technology to new heights and broaden our impact across science and medicine. We hope you will follow us on our journey on X, LinkedIn, and BlueSky as we lead genomics innovation to an insightful and healthy future. 

 

Happy New Year from our team at Phase Genomics!

 

 

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

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.