Is it time for sequencing entire antibody repertoires?


Continuing on the theme of immunosequencing, this post is about Atreca, Inc., founded in 2010 in San Carlos, California, and funded by the Bill & Melinda Gates Foundation. I first heard about this company a year ago from its co-founder Prof. Robinson of Stanford. As he explained in his talk given at Scripps, the company utilizes a novel HT technology, called Immune Repertoire Capture™, allowing to isolate B cells (plasmablasts, or plasma B cells producing antibodies, precisely), to barcode and sequence their cDNA, and finally to perform bioinformatics analysis (building a tree from comparison of antibody chain sequences). In the result, in two weeks, the whole antibody repertoire of an individual is decoded, and most importantly the pairing between light and heavy chains of each antibody is established because the technology allows to barcode each cell individually. That allows to get the whole makeup of an in antibody repertoire, frozen in time, and to see the rare clone families of antibodies, immunodominant (recognizing specific antigens) antibodies and also memory B cells, which would look like single branches on the dendogram of all antibodies (or B-cells, which is the same here as each B cell produces one type of antibody).

Applied to human disease, Immune Repertoire Capture™ is an engine for the discovery and development of antibody-based therapeutics, vaccines, diagnostics, and research reagents in therapy areas including cancer, infectious disease, and autoimmune disease.

How could it be? One example, take a cancer patient who is a long term non-progressor and look into which unique antibodies she produces that progressors do not — those antibodies can be studied to become antibody therapeutics against that form of cancer.

How is the company doing today? Unfortunately, not much info can be found in the news for the last year, except about 3 rounds of financing, two of which are debt financings, and a job ad on BioSpace for a Research Associate, versed in PCR and NGS. The company website is dated by 2012. Searching for Atreca, LinkedIn returns 20 profiles. The concept looks right and timely. Or, overwhelmed by genomics data, the world is not ready to deal with yet another deluge of big data?

Human Longevity, Inc. plans to overrun BGI

It is already three months as Human Longevity, Inc. was officially announced. The company now has a beautifully designed website and announcements about new executive hires.  The caliber of executives points at the company plans to grow huge and grow fast; thus CIO comes from AstraZeneca, where he was the Vice President, R&D IT responsible for the global IT organization services, analytics and infrastructure supporting drug discovery and development, leading a global team of approximately 300 and was accountable for the more than $120 million R&D IT budget. The company is also building a computing and informatics program and facility in Singapore.

BioIT World was one of the first to write about the company’s launch (for more news check the company’s website):

In a move that would be shocking from almost anyone else, Venter declared that his brand-new company’s sheer sequencing power will be leapfrogging the world’s best-established genomic research centers, such as the Broad Institute.

The company has acquired 20 the latest Illumina’s HiSeq X Ten machines ($1 million a piece), which would allow for sequencing full genomes of 40,000 people a year. For comparison, BGI by the end of 2013 had already sequenced 57,000 individuals. HLI doesn’t even need to compare itself with BGI as it plans to rapidly scale to 100,000 human genomes a year (considering that Illumina is among investors).

Human Longevity will also be characterizing at least some participants’ microbiomes, and, in partnership with Metabolon of North Carolina, their metabolomes, or the constantly changing array of small molecules present in the body. On top of that, said Venter, “we will be importing clinical records of every individual we’re sequencing,” in order to bring on board crucial phenotypic data.

The goal is to integrate this mass of data for new discoveries that can wed individuals’ own genetic variants, the composition of their bacteria, the molecules in their blood, and most importantly, their medical histories. Venter stressed that his aim is to enable predictive and preventative medicine for healthy aging, discovering early warning signs for susceptibility to chronic illnesses like cancer, Alzheimer’s, and heart disease, as well as new interventions tailored to each individual’s distinct profile. “We think this will have a huge impact on changing the cost of medicine,” added Venter.

A longer-term goal is to translate some of this information into stem cell therapies, an application that ties Human Longevity to Venter’s existing company, Synthetic Genomics.

But the goal of this year is sequencing genomes of cancer patients in collaboration with the UCSD Moores Cancer Center.

What exactly the company is going to do with all these data? Do research and publish papers? Yes, and some of principal scientists hired by the company got appointments at Craig Venter Institute. Sell data and the results of analysis? Yes. “Venter and his colleagues also held out the possibility of other commercial products and properties emerging from the company’s basic research.” The company is also actively hiring, and not only computational professionals but clinical and wet lab scientists as well. Here are some more about the company mission from job ads:

HLI will develop the most comprehensive gene-phenotype database in the world, with phenotype information deriving from molecular, physiologic, clinical, microbiome and longitudinal data assays. This database will be mined for biological meaningful patterns that can lead to better diagnostics, therapeutic targets and next-generation cell-replacement therapies.



23andMe doesn’t want people to wait around for 10 years for personalized medicine

Human Chromosomes

Eric Topol interviews Anne E. Wojcicki, co-founder and CEO of 23andMe.

Ms. Wojcicki: [We have] 650,000 [genotyped individuals] now. We are by far the largest. It is phenomenal. When you look at some of our papers, and we say that we had 40,000 people with asthma, and 150,000 controls, our numbers are genuinely huge. My inspiration was my father. He’s a particle physicist, and they collect really big data. He used to laugh at clinical trials. He would say, “Three hundred people — what is this?” So my goal was always to get huge numbers to really understand how things work. The price point has dramatically dropped, and that has really spurred the volume.

… everything I see the Obama administration doing is pushing individuals to take more control of their health.

You can already see what the Beijing Genomics Institute is doing. It is the largest in the world. They have massive interest in getting everybody genotyped or sequenced. Saudi Arabia announced plans [to genotype] 100,000 individuals. The United Kingdom is doing 100,000; Scotland has a big program. The rest of the world is moving forward aggressively with this, but we are somewhat stuck. It’s going to happen, and overwhelmingly it is going to improve healthcare. So how do we do that?

Ms. Wojcicki: The way I run the company is to think about if I were sick with a disease; what would I want to happen? If you have a child with sarcoma, you don’t care whether Pfizer or Glaxo or Hopkins or Harvard gets the data. You just want someone to do something with the data. Rather than saying that we are going to monetize and do all of these things, I point the finger at all of the pharma companies and groups who are just sitting on frozen piles of data because they don’t want to do anything with it yet. I want everybody to start to use the data to do something good. Otherwise, for this child with sarcoma, what’s going to happen?

Dr. Topol: When you have a million or even 10 million people, and you can find these rare variants that a lot of other people can’t find, that’s an exciting opportunity. We are going to watch this and follow along with you.

Ms. Wojcicki: That is definitely the direction in which we are going.

See this my post about BGI.

To GitHub or not to GitHub?


I wanted to write about open source for a while. Then I saw in several bioinformatics job postings an experience with open source software being listed among desired skills — something I never saw before. Then I bumped into an article in a paper version of Computerworld “Saying Yes to open source” and the following: Netflix is built on open source — since its so low priced service; Kaiser Permanente has been using GitHub since 2011.

Well, what is open source? Wikipedia says: “open source is a development model that promotes a) universal access via free license to a product’s design or blueprint, and b) universal redistribution of that design or blueprint, including subsequent improvements to it by anyone” and adds that Wikipedia is an example of applying open source outside the realm of computer software. Inside, the best example of an open source software would be Red Hut Enterprise Linux; while Unix, which I for example use on my MacBook, is not open source. RStudio is an open source IDE for R programming language. Eclipse, one of my favorite IDEs for whatever language, is also open source allowing to anyone to edit existing and to  write new plug-ins. A lot of commonly used bioinformatics software  is open source: Jmol and RasMol viewers, BioPython, BioJava, Bioconductor (and other R packages in CRAN), Galaxy — a workflow web-based system for analysis of genomics data and integration of data from UCSC Genome Browser and user data, and many other.

On another side of this free open source paradise is code hosting web repositories. And while many of them have been set up in the last 15 years, only the oldest, SourceForge (hosts more than 430,000 projects and has more than 3.7 million registered users, by Wikipedia), and the youngest, GitHub (hosting over 11.7 million repositories makes it the largest code host in the world), are the two everyone can name on-the-spot.

GitHub seems to be one to go with, for now. I first encountered GitHub last summer when my summer high school students refused to use SVN and sent me a link to GitHub. Now they have something to show up to the world :). We haven’t embraced GitHub at work yet, while are considering to use it for showing up the code (it is not free for private developments). While according to some posts it is worthwhile to pay and transition to GitHub for private developments as well.