dvdt
Joined 16 years ago
Joined 16 years ago
We're recently opened up a position for a Staff Software Engineer (https://apply.workable.com/billiontoone/j/2F0405817C/).
If you're interested, please reach out to me directly at [email protected]
BillionToOne develops innovative diagnostics tests that can affect the lives of millions of patients. Our QCT technology platform improves the resolution of cell-free DNA testing by >1000x fold and enables novel tests for both prenatal and oncology care. We've raised over $30M and have launched multiple clinical products in the past 2 years, including an FDA authorized COVID-19 test.
We are hiring a senior engineer (5+ years experience) to build internal APIs, bioinformatics procecessing pipelines, laboratory automation tools, and help manage CI/CD. We use python, django, rabbitmq, circleci, dbt, postgres, heroku, aws, and a variety of other tools.
If you have experience in full stack web development, love seeing your work positively affect your colleagues, and thrive in a fast-paced entrepreneurial environment, this could be a great opportunity for you.
Please contact me directly at [email protected] if interested.
- ClojureScript with Figwheel and the web browser
- Clojure with Emacs Cider, Clojure with Cursive
- R and Rstudio
- Matlab
- ipython jupyter notebook
- Pycharm debug breakpoints that are triggered by unittests (Running the unittest to initiate a python repl at the breakpoint)
Purely speculative, but I think if swabs remain an issue for too long, alternatives could start coming online, such as even using qtips + saline (no idea if it works, it's just an example). The current swab + Universal / Viral Transport Medium combo is optimized for flexibility; it is designed to work across a very broad range of viruses and bacteria that have different viral loads and shedding characteristics. The current pandemic is pretty much COVID-19 only, so I think it's a priori feasible that a specimen collection procedure can be found that uses common materials. We did try early on to see if saline or other buffers affected the performance of the assay, and it worked fine in those conditions.
We use fairly standard chemicals. I haven't heard from our suppliers about shortages for the chemicals we use. Chemicals and enzymes tend to be relatively fast to scale up for bulk manufacturing.
There's always manufacturing risk that a product will not work as expected. In fact, the first COVID-19 test developed by the CDC did not work as expected, and this delayed testing by several weeks. We de-risk this as much as possible by performing experiments as early as possible, akin to the fail fast mentality of checking for the highest risk failure modes first. Since we don't have a national healthcare system in the US, the manufacturer takes on the vast majority of the risk of a defective product.
The FDA has recently made clear that no at-home self-collection tests are allowed (for now): https://www.fda.gov/medical-devices/emergency-situations-med...
The way currently available COVID-19 testing works is by detection of viral RNA. Since the amount of viral RNA in a patient sample is too low to detect directly, we first need to amplify it by PCR. However, this viral RNA is packaged within all sorts of proteins and lipids that could make it inaccessible to amplification unless they are first purified away. Furthermore, the sample is shipped in "viral transport medium", which is essentially a cocktail of chemicals designed to preserve the virus. Unfortunately, these preservatives often have the side effect of interfering with PCR amplification, so these too need to be purified from the sample.
However, since RNA extraction is usually the most laborious part of the assay, there has been a lot of interest in optimizing the amplification so that it is resilient to all of these impurities. The preprint referenced in our manuscript (https://www.biorxiv.org/content/10.1101/2020.03.20.001008v1) gave us the initial idea that this could be possible, and much of it comes down to the choice of amplification method (e.g. choice of enzymes and buffers) that you choose.
However, even when you choose a "good" enzyme and buffer, you will still suffer an amplification penalty, and this will cause you to return a false-negative on some affected samples because there was so little virus in the sample to begin with. The innovation we have is to spike-in a correspondingly low level of DNA to the reaction mixture. That way, if you see the low level of DNA without seeing any viral signal, you can be assured that the amplification still worked and that there truly is no virus in the sample.
I think that where the Abbott machines might hit a wall is that they are one at a time, and they require Abbott's consumable test cartridge and device to run (think printer ink / printer). I don't have any firsthand knowledge, but I would anticipate that it is difficult to scale-up manufacturing of the devices rapidly enough to keep pace with the pandemic growth.
We absolutely need contact tracing to find everybody who needs to be tested. We're not working on scaling up contact tracing, but I think several people in the tech community are working on making that easier to perform at scale.
The core of our machine learning is Ax=b :grins:
More seriously, the main reason why traditional sanger sequencing can't be used for COVID-19 testing is because it would be unclear whether a lack of signal is truly due to lack of virus, or if it is just because the assay failed (happens all the time!)
What we've done is introduce a reference sequencing signal that is biochemically very similar to viral RNA, but produces a distinct vector of electrical signals that is different from the signals emitted by viral RNA. Since we know what both the reference and viral signals look like, we can perform linear regression analysis to fit the linear combination of viral and reference signals that best match our data.
BillionToOne has developed a DNA molecular counter that increases cfDNA diagnostic resolution by over 1,000x. BillionToOne's first product, UNITY, is the first and only non-invasive prenatal test that directly screens an unborn baby for the most common and severe genetic disorders using only a single tube of blood from the pregnant mother without the invasiveness of amniocentesis.
BillionToOne is ranked at the top 5% of Y Combinator companies and has raised $300M+ in funding from prominent VC firms.
We are hiring a Staff Software Engineer to scale up compute-intensive bioinformatics workflows and build infrastructure tools that enable scientists, bioinformaticians and other technical teams at BillionToOne to robustly write and deploy code.
Tools we use include: python, Django, AWS, Terraform, Sentry, and Datadog.
Apply here: https://boards.greenhouse.io/billiontoone/jobs/4203247005