Category: Science

Unlocking New Frontiers in our Understanding of Human Disease through Deep Learning and Three-Dimensional Genomics

Posted on July 16, 2020 by - Genomics, Hi-C, Proximo, Science

 

By Ivan Liachko, Ph.D – Founder & CEO, Phase Genomics

 

As we enter the era of personalized medicine, novel genomic technologies are enabling a much deeper understanding of the biology of individual people. Such knowledge improves our ability to detect and diagnose diseases, offering personalized treatments that leverage each person’s unique genetic makeup for maximum safety and efficacy. However, human biology is very complex, and – despite decades of advances in DNA sequencing and analysis methods – we have yet to realize the full promise of genomics-enabled personalized medicine.

To truly realize the benefits of genomics in healthcare, we must go beyond basic sequencing efforts that look at mutations or gene expression patterns, and study the higher-order structure of the genome, i.e. its organization and shape. These are known to drive many kinds of human diseases including cancer, autism, and infertility.

Phase Genomics has commercialized a new genome sequencing technology that enables us to look beyond the genetic code and characterize the higher-order organization of genomes. This technology, called “proximity ligation“, not only detects sequence differences. It enables us to identify and characterize changes in genome structure called “structural variation”, as well as patterns in the three-dimensional organization of the genome.

Phase Genomics has developed and commercialized several products that leverage proximity ligation in different research contexts. We are now combining the technology with deep learning to deliver new research and diagnostic capabilities for human disease.

The new, revolutionary approach currently in development at Phase Genomics combines deep learning with several other supervised and unsupervised machine learning methods to identify, recognize, and contextualize structural variants or other perturbations in a human genomic sample, based on recognizing structural signatures hidden deep within the proximity ligation data. Once variants are detected, they can be connected to the body of research and medical literature to provide actionable clinical information. The high-throughput nature of both the biological and computational underpinnings of this technology means that the approach is not only more effective than other methods; it is also faster, cheaper, and more scalable.

Phase Genomics will be announcing additional products delivering new dimensions of genomic insights into human disease in the coming months. For now, the research, development, and testing continue.

Built on Amazon’s AWS cloud computing and machine learning technology, and in consultation with 1Strategy – a leading cloud architecture and development firm – Phase Genomics’ proximity ligation plus deep learning technology is poised to open new frontiers in human clinical diagnostics.

Q&A with Co-Authors About Bees, Mites, and Their Genomes

Posted on April 5, 2019 by - Hi-C, Proximo, Science

Co-authors Dr. Alexander Mikheyev of the Okinawa Institute of Science and Technology and Dr. Jay Evans from the U.S. Department of Agriculture’s Bee Research Laboratory had such great answers that we wanted to share some of them. This research was also featured in ZME Science.

Why is it important and useful to have a high-quality genome for Varroa species? Is there any combined value with the recently published bee genome?

Dr. Mikheyev: Understanding the mechanisms of parasitism requires detailed information about the organization of the genome. Many recent ideas for fighting Varroa rely on molecular tools, which in turn rely on genomic data. Furthermore, a good genome enables us to understand the coevolutionary interactions between mites and the bees. For now, our studies are focused on understanding how the mite has evolved to become a better parasite. However, my lab is also looking at the bee side of the coevolutionary interaction. Having high-quality genomes for both will allow us to identify genomic regions and genes involved in coevolution.

Why did you choose to use Hi-C? Why did you need chromosomes for your genome assembly?

Dr. Evans: From prior genome efforts, we had no information on the physical positions of mite gene features. Now with these in place, we can leverage synteny information from other arthropod genomes and narrow searches for some hard-to-find proteins like olfactory receptors, which often occur in clusters. Generally, the improved genome helps us know what might be unique to Varroa — and therefore a novel clue into their biology and control.

Dr. Mikheyev: One element of this study was to look at patterns of gene duplication, which could indicate diversification of particular gene families. Having a contiguous genome allows us to better localize these duplications and confirm that the different copies are homologous. In the future, when we’ll be looking at signatures of selection, a really powerful approach is to identify genomic regions with reduced genetic diversity. Having adequate chromosomal scaffolding will be essential there.

What genomic clues were found in the two Varroa species that may contribute to parasitism?

Dr. Evans: We found a clear set of genes for the proteins — olfactory receptors and others — that these mites must be using to react to their bee hosts. Hopefully, knowing these proteins will lead to smarter controls and insights into why each species maintains a specific host preference.

Dr. Mikheyev: For us, the most striking finding is this: The evolutionary trajectories of both mites, despite their similarities and close relatedness, were completely dissimilar. At this stage, it is still a bit hard to tell specifically what the selective pressures were and what the mites are adapting to. Curiously, in both species, genes involved in stress tolerance and detoxification were already under selection. This most likely happened before they ever faced miticides and suggests that they may have pre-adapted strategies for dealing with our chemical warfare strategies against them. We hope to tackle this in an upcoming study looking at population-level differences between mites adapted to original and novel hosts.

How do you hope these genomes will be used to help save honey bees?

Dr. Evans: Prior genome drafts had enough gaps that we missed candidate proteins for mite control. These mite genomes will lead to focused efforts to target pathways or traits not found in bees by techniques like small molecules, biological controls, and RNA interference.

Dr. Mikheyev: They can be used to develop new strategies for Varroa control. Also, in upcoming studies looking at how mite populations are adapted to original vs. switched hosts, we hope to identify genes and genomic regions that are specifically important in host switches.

Is there any genomic evidence that the western honeybee could be developing resistance to these pests?

Dr. Evans: Yes. Some bee breeders are targeting these traits, from behaviors to virus resistance. A recent, improved assembly of the honey bee genome — aided in part by Hi-C sequencing — is being used for trait identification and marker-assisted breeding right now.

Dr. Mikheyev: They most definitely are. Intriguingly, wild populations of honey bees seem to evolve tolerance to the mites relatively quickly. In one of my favorite studies, a USDA-monitored population in Louisiana first saw high mortality upon the arrival of Varroa, but a few years later colonies lived even longer than before. There are resistant populations known in the U.S. and in Europe, and resistance is a trait that can be selected. How this adaptation takes place in the bee is really interesting, and something we’ll continue to look into.

Isolating Varroa mites from bees involves a creative use of powdered sugar. How do you think this technique came about?

Dr. Mikheyev: We don’t know. The papers describing this method are pretty prosaic. It seems that in the late 1980s, wheat flour was used to control Varroa by knocking them off the bees — and eventually, someone tried sugar.

Dr. Evans: Since they’re attached to their bee hosts, researchers have used a variety of ‘irritants’ to get mites to fall off. Powdered sugar is safe for the bees and might even be an extra calorie boost. The bees pull sugar from each other and the mites fall off — mostly because of the sugar itself, but also because the grooming bees find them.

What is your favorite weird food that involves honey?

Dr. Mikheyev: It’s not really a food since it is honey, but I love the fact that the giant honey bees of Nepal make psychedelic honey from Rhododendron flowers. The story is worth tracking down for no other reason than the dramatic photos of the men that harvest this honey from sheer cliffs.

Dr. Evans: Honey lemonade. Sorry, I am required by my kids to not say weird things.

Lil BUB Aids in Discovery of New Bacteria

Posted on August 1, 2018 by - Hi-C, Metagenomics, ProxiMeta, Random, Science

Published author, talk show host, movie star, musician, and philanthropist—Lil BUB has now also helped to discover novel microbial life living in her gut in collaboration with AnimalBiome, KittyBiome, and Phase Genomics. Enter to sequence your cat’s microbiome in our #Meowcrobiome twitter raffle!

 

We live in an era of discovery, especially as it relates to the microbiome and how microbial diversity influences our world, our health—and even our pet’s health. To better understand the microbial life of our feline friends, Lil BUB volunteered to sequence her gut microbiome. Thanks to a recent collaboration with AnimalBiome, KittyBiome, and Phase Genomics, Lil BUB helped discover 22 new microbes living in cats which, in time, could reveal new insights into cat health and happiness.

When KittyBiome started back in 2015 with an intent to understand the cat microbiome,  Lil BUB’s owner Mike “Dude” Bridavsky provided a sample of her poop to be analyzed. Because of Lil BUB and over 1,000 other cats, KittyBiome’s microbial census will help us identify what microbes are associated with healthy cats and work towards helping cats with Inflammatory Bowel Disease (IBD), diabetes and other ailments likely to be associated with the microbiome.

 

USING GENOMICS TO FIND MICROBES

Late last year, Phase Genomics offered to analyze samples from Lil BUB and another cat, Danny (belonging to Jennifer Gardy—a microbiologist at the University of British Columbia and science TV host), using our ProxiMeta™ Hi-C Metagenomic Deconvolution platform to obtain complete microbial genomes from their samples.  This method solves a huge problem in microbiome research—how to tell apart different species when their DNA is all mixed up in one sample (imagine a thousand jigsaw puzzles mixed together).

ProxiMeta Hi-C revealed about two hundred different species of microorganisms living in Lil BUB and Danny’s poop, many of which have never been seen before. The genome sequences of the microorganisms found in these samples were analyzed using our software and other microbiome analysis tools to measure the quality of the different assembled genomes and to see if those genomes matched any known microbes (Lil BUB’s and Danny’s data are available for free on our website). Without using our ProxiMeta Hi-C platform to extract these genomes, many of them would have been undetectable and gone unseen.

Lil BUB and Danny the Cat

Phase Genomics sequenced both Lil BUB (left) and Danny’s (right) poop samples.

 

OVER 20 NEW BACTERIAL GENOMES DISCOVERED

Lil BUB being heldTogether, Lil BUB and her buddy Danny carry 22 previously undescribed bacterial species in their guts.  Lil BUB’s poop sample had 13 species and Danny’s sample had 9 species that have never before been fully sequenced or characterized.

These new bacterial species mostly belong to the order Clostridiales, and the team is currently analyzing the genomes to better characterize them. This discovery will help continue to build a database that contains cat bacteria that are new to science, so we can better identify the contributions of the microbiome to various health conditions.

This cool discovery, made with the help of Lil BUB and Danny, highlights that there’s a  universe of undiscovered microbial life out there. If we found 22 potentially novel species in only two cats, just imagine what else is out there, and what the implications might be for new ways to support and improve the health of our pets.

 

WHO ARE OUR HERO CATS?

Lil BUB is a one of a kind critter, made famous on the Internet due to her adorable genetic anomalies. She is a “perma-kitten”, which means she will stay kitten-sized and maintain kitten-like features her entire life. She has an extreme case of dwarfism, which means her limbs are disproportionately small relative to the rest of her body. Her lower jaw is significantly shorter than her upper jaw, and her teeth never grew in so her tongue is always hanging out. Lil BUB is also a polydactyl cat, meaning she has extra toes – 22 toes total!  Lil BUB and Her Dude travel all over the country raising hundreds of thousands of dollars for animals in need.

Danny, an exotic shorthair with a face much like Grumpy Cat, is equally adorable.  He is the companion cat of one of KittyBiome’s original researchers, Jennifer Gardy, and was one of the very first cats to lend his poop profile to the KittyBiome initiative.  He is a very healthy cat and his microbial profile has helped us learn what a balanced gut in cats looks like.

WHAT’S NEXT?

Phase Genomics and AnimalBiome are eager to learn more about these newly-discovered bacterial species. They hope to work with the scientific community to analyze, identify, characterize and publish these genomes, starting with exploring their identities based on 16S rRNA and other marker genes.

HOW TO GET INVOLVED

  • Help characterize the new bacteria: If you know of a researcher, scientist or cat-lover who would like to help us, we are soliciting input on the analysis that needs to be done to properly characterize and publish these genomes. Participants who contribute in a substantive manner to the project will be co-authors on the publication. All data associated with the project will be deposited into publicly available databases and we will publish the findings in open access journals, so all pet lovers can read them. We will hold a raffle to award one lucky contributor a free Hi-C sample kit from Phase Genomics. If interested, contact us at team@animalbiome.com to learn more.
  • Name the new bacteria: We’re looking for input from the community on what we should name these 22 new bacteria, so if you have any fun ideas, please drop us an email at team@animalbiome.com. The format should follow standard practices of scientific nomenclature, so it should be constructed like this: “Clostridium _________.”
  • Submit your pet’s sample for genomic research: If you don’t win the raffle and still want your pet to contribute to scientific knowledge through the identification of new bacterial species, please contact us at team@animalbiome.com. We can provide you with the details and pricing involved for us to identify new species in your cat or dog through in depth analyses like we did for Lil BUB and Danny using the Hi-C approach pioneered by Phase Genomics, which would also result in a publication.

Improving databases of the microbiome of cats (and dogs) with new bacteria like this could help us learn more about how the gut microbiome helps support the digestive health of all pets.

ENTER YOUR CAT IN OUR TWITTER RAFFLE

Phase Genomics, AnimalBiome and KittyBiome are hosting a twitter raffle where you can enter to sequence your cat’s microbiome! All you have to do is go to either the Phase Genomics’ or AnimalBiome’s original tweet of this blog, retweet it with a picture and introduction of your cat with the hashtag #Meowcrobiome. On August 8th 2018, we will randomly draw one (1) winner whose cat poop will be scientifically analyzed by Phase Genomics with ProxiMeta Hi-C to search for novel microbes, and three (3) additional winners whose cat poop will receive a Kitty Kit to have their cat’s poop analyzed by Animal Biome to compare their cat’s gut to healthy cat guts.  Send in your cat’s poop, and you too can help discover new microbial life!

LIL BUB AND DANNY’S STORY FEATURED ON GEEKWIRE PODCAST

GeekWire discussed Lil BUB, Danny, and the new bacteria found in their poop in their weekly Week in Geek podcast. Check out the full podcast on their website (the segment begins around 22:58), or play just the segment about Lil BUB and Danny below.

 

 

A sweet new genome for the black raspberry using Proximo™ Hi-C

Posted on March 28, 2018 by - Genomics, Hi-C, Proximo, Science

Black raspberries

The Black Raspberry, known for its sweetness and health benefits studied further to reveal its chromosome-scale genome.

What is a black raspberry you may ask? Jams, preserves, pies, and liqueur are just a few of the delicious products made with black raspberry. The black raspberry offers much more beyond its exquisite flavors. For instance, did you know it contains a compound called anthocyanins that is used as a dye? It is also used in anti-aging beauty products and contains compounds that may help fight cancer. The useful properties of black raspberry are encoded within the genome.

A multi-national team of scientists have built a full map of the Black Raspberry genome. Teams from New Zealand, Canada, and the U.S.A. contributed to the project led by Drs. Rubina Jibran and David Chagné. The work was published in Nature, Horticulture Research. In the project they leverage Proximo™ Hi-C to order and orient short-read contigs into chromosome-scale scaffolds.

A chromosome-scale reference genome is an important step for basic biology and for breeding programs. Breeders can use this genome while crossing plants to select for traits like color or taste.  To learn more about how Hi-C technology was used to improve the black raspberry genome we contacted Dr. Chagné and Dr. Jibran for a Q&A session. We also wanted their take on the scientific value of Proximo Hi-C and to share their experiences working with us.

 

What is a black raspberry? How is it different from the blackberries we have in Seattle?

The black raspberry we used is no different from the ones found in Seattle. Actually, I remember seeing some black raspberries (also called black-caps) at Pike market few years ago! Washington and Oregon are the largest producers of this delicious crop. Raspberries belong to the genus Rubus, which includes red (Rubus idaeus) and black (R. occidentalis) raspberries, blackberries, loganberries and boysenberries.

 

There are many curious uses of black raspberries, what’s yours?

Black and red raspberries are great on top of Pavlova, alongside slices of kiwifruit. Pavlova is New Zealand’s iconic dessert served around Christmas time, which is the berry fruit season down under here.

 

What are molecular breeding technologies? What are some of the traits in black raspberry you’d like to breed for?

Molecular Breeding techniques use DNA to inform selection decisions. My colleague Cameron Peace from Washington State University did a very good review about the use of DNA-informed breeding in fruit tree.  Plant & Food Research is leading in the use of molecular tools for breeding fruit species, for example we are using genetic markers to predict if apple seedlings carry certain loci for black spot resistance or if they are likely to be red fruited. The breeding goals for Plant & Food Research’s raspberry breeding programme are high fruit flavour, berry anti-oxidant content, pest and disease resistance and higher productivity.

 

The initial black raspberry genome assembly was built from short-read data. Why did you choose to scaffold the short-read contigs rather than create a new long-read assembly? Would you get chromosome scale contigs from a long-read assembly? 

Actually we took both approaches and we decided we would like to see how much of the short-read assembly we would be putting together using Proximo Hi-C. A long-read based assembly will be released soon and the comparison of both assemblies will be extremely informative on what strategy to use for future assemblies of other crop species.

 

How did you validate the Proximity Guided Assembly (PGA) scaffolds? How did you correct errors in the scaffolds?

The PGA for black raspberry was first validated by aligning it to a linkage map and then by aligning it to the genome of strawberry (Fragaria vesca) as they have syntenic genomes.

 

What was the process like in working with Phase Genomics? Would you recommend them to your colleagues?

I enjoy a lot working with Phase Genomics. Black raspberry is not the first genome that we collaborated with Phase Genomics, as we had assembled genomes for kiwifruit and New Zealand manuka previously. The way we work with Phase Genomics is very iterative and they are excellent at trying new methods and assembly parameters until we are satisfied with our assemblies. Every organism has its own challenges when it comes to genome assembly and working with Phase Genomics in a very collaborative way is extremely useful. I have recommended Phase Genomics to colleagues.

Uncovering the microbiome: What will you do with metagenomics?

Posted on March 1, 2018 by - Hi-C, Metagenomics, ProxiMeta, Science

In this Nature Microbiology blog post, Mick Watson shares his journey into the depths of the rumen microbiome. Read more here to learn how Phase Genomics ProxiMeta Hi-C Metagenomic Deconvolution techniques are helping investigators advance their metagenomic research in complex samples. This study successfully assembled 913 genomes and will help to improve our understanding of the microbial population in cow rumen in an unprecedented way using these new metagenomics techniques. We look forward to seeing what else comes from Microbiome 2.0. and are proud to be a part of this impressive piece of work.

Hundreds of Genomes Isolated from Single Fecal Sample with Hi-C Kit

Posted on October 18, 2017 by - Hi-C, Metagenomics, ProxiMeta, Science

 

Hi-C Kit Microbiome

A Phase Genomics Hi-C kit for any sample type are now available!

Phase Genomics recently launched its ProxiMeta™ Hi-C metagenome deconvolution kit + software
product, enabling researchers to bring this powerful technology (previously only available through the ProxiMeta service) into their own labs. A new paper posted to biorxiv describes the results of employing ProxiMeta technology to deconvolute a human gut microbiome sample.

 

In the paper, ProxiMeta was used on a single human gut microbiome sample and isolated 252 individual microbial genomes or genome fragments, with 50 of these genomes meeting the “near-complete” threshold typically used as the standard according to the CheckM tool (>90% complete, <10% contaminated). Examining the tRNA and rRNA content of the genomes found 10 to meet “high-quality” and 75 to meet “medium-quality” thresholds. Additionally, 14 of the genomes represent near-complete assemblies of novel species or strains not found in RefSeq, showing that even after many years of research, there remain numerous unknown microbes in the human gut that are discoverable with new approaches.

 

ProxiMeta’s results were compared to those achieved with MaxBin, a common tool used to perform metagenomic binning based on heuristics such as shotgun read depth and tetranucleotide profiles. MaxBin was able to create 29 near-complete genomes (cf. 50 for ProxiMeta), with only 5 meeting high-quality (cf. 10) and 44 meeting medium-quality (cf. 75) thresholds based on tRNA and rRNA content. In terms of ability to construct similar sets of near-complete genomes, ProxiMeta and MaxBin constructed 27 of approximately the same genomes, with ProxiMeta constructing an additional 32 genomes that MaxBin did not, and MaxBin constructing 9 genomes that ProxiMeta did not. ProxiMeta’s assembled genomes also exhibited a much lower amount of contamination than MaxBin’s assembled genomes, with 43% of MaxBin’s assemblies exceeding the 10% contamination limit that is the typical standard for genome quality, compared to only 2% of ProxiMeta’s assemblies.

 

Other results unique to ProxiMeta include the discovery of near-complete genomes for 14 novel species or strains and various associations of plasmids with their hosts. Of the 14 novel genomes, 10 appear to be of the class Clostridia, a common group of gut microbes that are poorly characterized due to their difficulty to culture.  ProxiMeta also assigned 137 contigs containing plasmid content to a cluster and identified candidate plasmid sequences as being present across multiple, distantly related bacteria. For example, ProxiMeta placed a known megaplasmid into an assembly for Eubacterium eligens that included homologous plasmid sequences placed into several other genomes, suggesting either the presence of the megaplasmid into other species, or variants of the megaplasmid being found on other mobile elements spread through the metagenome.

 

The depth of the resulting data and results offers the opportunity to learn much more about this microbial niche and research continues to unlock new discoveries about this community. Phase Genomics is thrilled to be able to offer all researchers the same new power to dig deeper into their mixed samples than ever before, especially now with a product that puts the power of discovery in their hands.

 

To learn more about ordering our kits or services, just send us an email at info@phasegenomics.com

Orphan Crop Gains Reference Genome with Proximo Hi-C

Posted on September 1, 2017 by - Genomics, Hi-C, Proximo, Science

Amaranth genome assembly brought to the chromosome-scale using Phase Genomics’ Proximo Hi-C technology. 

 

“Orphan crops” are growing in popularity because they have the potential to feed the world’s expanding population.  You may have heard of orphan crops like quinoa or spelt, but have you heard of amaranth?  The amaranth genus (Amaranthus) is a hearty group of plants that produce nutritious (high in protein and vitamin content) leaves and seeds.  Amaranth species grow strongly across a wide geographic range, including South America, Mesoamerica, and Asia.  Amaranth was likely domesticated by the Aztec civilization and has been a staple food of Mesoamericans for thousands of years. Breeders wish to enhance amaranth’s beneficial properties like drought resistance, nutrition, and seed production to improve the usefulness of amaranth as a food source.  However, effective plant husbandry requires genetic and genomic resources, and building these resources has been inhibited by the high cost of genome sequencing and assembly.

 

Genome assembly Hi-C Orphan Crop

Dr. Jeff Maughan (left) and Dr. Damien Lightfoot (right), are the primary authors of the amaranth genome paper.

Dr. Jeff Maughan, professor at Brigham Young University, is a champion of orphan crop genomics.  Over the past year, Dr. Maughan and his team built a reference-quality amaranth genome on a tight budget.  They built upon an earlier,  short-read assembly by adding Hi-C data, which measures the conformation of chromatin in vivo, as well as low coverage long reads and optical mapping data.  After using optical mapping to correct assembly errors in the short read assembly, the Hi-C data was used to cluster the short genome fragments into nearly complete chromosomes using Phase Genomics’ Proximity-Guided Assembly platform, Proximo™ Hi-C, Then, the long reads were used to close remaining gaps on the chromosomes.  This cost-effective strategy recovered over 98% of the 16 amaranth chromosomes.

 

The completed reference genome provides an important resource for the community and will boost the efforts of plant breeders to unlock more agricultural benefits for amaranth.  In their paper, Dr. Maughan’s team demonstrated the utility of the reference quality genome in at least two ways.  First, they looked at chromosomal evolution by comparing the amaranth genome to the beet genome, which enables researchers to better understand amaranth in the context of how plants evolved, and second, they mapped the genetic locus responsible for stem color, which clarifies the scientific understanding of a useful agricultural trait.  Dr. Maughan points out that both of these experiments would have been impossible without the chromosome-scale genome assembly afforded by Proximo Hi-C.

 

A high-quality reference genome is the first of many important steps towards creating a modern breeding program for amaranth. We contacted Dr. Maughan to learn more about how he is improving amaranth genomics and the importance of orphan crops.

 

What is an orphan crop? 

According to the FAO (Food and Agriculture Organization of the United Nations) the world has approximately 7,000 cultivated edible plant species, but just five of them (rice, wheat, corn, millet, and sorghum) are estimated to provide 60% of the world’s energy intake and just 30 species account for nearly all (95%) of all human food energy needs.  The remaining species are underutilized and often referred to as “orphan crops”.

 

How is genomics relevant to orphan crops?

Would you invest your entire 401K savings in just three stocks?  In essence, that is what we are doing with world food security.  This comes with tremendous risk.  If we are going to diversify our food crops, it will be with these orphan crops.  Modern plant breeding programs leverage genomics to significantly enhance genetic gain (yield), such methods will undoubtedly expedite the development of advanced varieties in orphan crop species.

 

What are the challenges facing researchers interested in orphan crop genomics?  How have you overcome them?

Funding has long been the main obstacle to developing genomic resources for orphaned crops.  The development of cheap, high-quality next-generation sequencing technology has dramatically ameliorated this problem – making genomics accessible for most plant species.

 

You used two scaffolding technologies for your assembly, Hi-C, and BioNano. How did they compare?

Both technologies are extremely useful and complementary but address different genome assembly challenges.  The Hi-C data allows for the production of chromosome length scaffolds, while the BioNano data allows for fine-tuning and verification of the assembly.

 

Beyond building a high-quality genome assembly, what other genomic resources are required to encourage the adoption of orphan crops?

While genomic resources (such as genome assemblies and genetic markers) are fundamental for developing a modern plant breeding program, often what is missing with orphan crops is the collection of diverse germplasm (or gene bank) that is the foundation of a hybrid breeding program.  The U.S. and other nations have extensive collections (tens of thousands of accessions) that serve as the genetic foundation for staple crop breeding programs – unfortunately, such collections are minimal or non-existent for orphan crops.

 

Who stands to benefit the most from a complete amaranth genome?  How do you disseminate your work to them?

We collaborate extensively with researchers throughout South and Central America, where amaranth is already valued as a regionally important crop.  Dissemination of our research occurs though traditional methods (e.g., peer reviewed publications) as well as through sponsored scientist and student exchanges.

 

Amaranth is used in a variety of interesting foods, what’s your favorite dish?

Alegría, which is made with popped amaranth and honey, and is common throughout Mexico.

 

Spotlight on Hi-C in Science: New Technologies Boost Genome Quality

Posted on July 7, 2017 by - Genomics, Hi-C, Proximo, Science

Science writer, Elizabeth Pennisi, outlines available genomics technologies that are helping researchers improve genome assemblies with a focus on Hi-C’s ability to bring genome assembly to the chromosome-scale.

This article, by Elizabeth Pennisi, focuses on how new technologies are making genome quality much better.  Long-reads, optical maps, and Hi-C data are being synergistically applied to improve modern genome assemblies including goat (Dr. Tim Smith), humming bird (Dr. Eric Jarvis), maize, and more.  Importantly, Hi-C provides the finishing touch to these genomes, by providing ultra-long contiguity information that can scaffold entire chromosomes. We, at Phase Genomics, are glad researchers have chosen Proximo Hi-C to scaffold the goat, hummingbird, and hundreds of other assemblies into contiguous chromosome-scale reference genomes.

 

Read the article here

Hi-C Used to Assemble Extremely Large, Difficult Barley Genome

Posted on April 27, 2017 by - Hi-C, Science

Barley is the 4th most cultivated plant in the world and has been a reliable food source for over 10,000 years. Genome Web reports on the exceptional state of the genome assembly and how researchers used Hi-C technology to tackle this extremely complex genome.

 

The barley genome, like many other grains, is notorious for being extremely difficult to assemble due to extensive polyploidy, long repeat regions, and its large genome size (5.3 Gb). However, the Barley Genome Sequencing Consortium (IBSC) used Hi-C to tackle this genome assembly, producing chromosome-level scaffolds representing over 95% of the genome in an attempt to understand the biology of this widely cultivated plant. After completing the assembly, the researchers began annotating the genome and identified over 87,000 different genes, publishing their findings in Nature.

 

Obtaining reference-quality assemblies for complex genomes, such as barley, used to be an extremely challenging endeavor. With Hi-C, obstacles like polyploidy and multi-Gb genomes are manageable due to its ability capture ultra-long-range genomic contiguity information from unbroken chromosomes, replacing the need for genetic maps. This ability enables researchers to answer questions otherwise difficult or impossible, including structural variation, complex gene structure, gene linkage, gene regulation, and more. While the researchers performed the barley assembly themselves, Phase Genomics’ Proximo Hi-C service makes it easy for any researcher to obtain similar results and has been used to assemble hundreds of genomes to chromosome-scale over the past two years, including complex genomes like barley.

 

Read more about the barley genome on Genome Web.

Spotlight on Hi-C in The Atlantic: The Game-Changing Technique That Cracked the Zika-Mosquito Genome

Posted on March 29, 2017 by - Genomics, Hi-C, Proximo, Science

One of the most prolific science writers, Ed Yong, profiles how Hi-C sequencing technologies can make genome assembly easier and more cost-effective than ever before. 

Science writer Ed Yong covers the narrative on the researchers’ tackling the disease carrying Aedes aegypti genome, and how Hi-C “knitted” the genome from 36,000 pieces into complete and contiguous chromosomes. Yong points out that the completed genome will not only help scientists better understand the biology of the mosquito at a much deeper level, but it also marks a technological pivot in genomics: Hi-C makes genome assembly cheaper, more accurate and faster than ever before. Also, mentioned in the article: our collaborator, Dr. Catherine Piechel’s newly published three-spine stickleback genome, and Dr. Erich Jarvis’s hummingbird were also cited as examples of the power of Proximo Hi-C scaffolding.

 

Read the article here

Papadum’s Recipe for an Outstanding, Chromosome-Scale Genome with Hi-C

Posted on March 6, 2017 by - Hi-C, Proximo, Science

Meet Papadum the Goat! Papadum is a descendent from a rare population of goats that used to inhabit the San Clemente Island, and notably, Papadum also now holds the world record for the most contiguous non-model mammalian genome.  The recipe for a his amazing de novo genome assembly? Long reads, optical mapping, and Proximo Hi-C genome scaffolding. Read NIH’s article about Papadum’s genome here.

 

The goat genome has been of scientific interest for several reasons: goats are important suppliers of milk, cloth, meat, and more. But prior to the Papadum genome, scientists’ ability to fully understand how the goat genome controls its biology was limited. As a part of the “Feed the Future” initiative, in 2014 the U.S. Agency for International Development awarded innovative scientists Dr. Tim Smith, Dr. Derek Bickhart and Dr. Adam Phillippy a grant to attempt to eliminate these limitations by assembling Papadum’s genome. As pioneers in the genomics field, the scientists teamed up to leverage two rather young technologies, long reads and Hi-C, to create an ultra-high-quality new assembly of the goat genome.

 

Their efforts ultimately led to the creation of the highest quality de novo genome assembly of a mammal to date and are published in Nature Genetics.  With this new reference-quality goat genome, scientists will have a better understanding of goat biology and health to guide better breeding decisions, improving traits like milk production, meat quality, and resilience from disease.

 

The Papadum genome assembly includes large DNA sequences called “chromosome-scale scaffolds” which are nearly complete representations of entire chromosomes from Papadum. These chromosome-scale scaffolds are critical achievement that allows far better understanding of the mechanics of the goat genome than earlier, less advanced results, which included thousands of tiny fragments of chromosomes and lacked the overall structure of the goat genome. The difference is not unlike having an entire intact book, versus a jumble of all the individual words from the book.

 

The ability to reconstruct nearly complete chromosomes was made possible largely by a new technique called Proximity-Guided Assembly, performed with Phase Genomics’ ProximoTM Hi-C scaffolding technology. This process was followed by a tool called PBJelly, which identifies and closes gaps (regions of uncertainty) in the chromosome-scale scaffolds. After Proximo and PBJelly, the resulting assembly included 31 chromosome-scale scaffolds containing only 663 gaps total across the 3 billion base pair diploid genome. Descended from research first published in 2013, Phase Genomics has since successfully demonstrated the success of the Proximo Hi-C scaffolding method in the genomes of plants, animals, fungi and more.

 

Papadum’s genome marks the beginning of an era where reference-quality genomes are achievable and affordable for any organism, not just extensively studied model organisms like mice, fruit flies, and humans. The availability of these extraordinarily complete genomes enables scientists to answer many new biological questions that have the potential to help farmers, government agencies, agricultural companies, and developing countries solve a significant part of the food security problem.

 

Read more about the grant, the scientists, and Papadum’s genome on the NIH’s National Human Genome Research Institute website.