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Cofactor Genomics (YC S15) Pursues RNA Testing, Offers Better Diagnoses Than DNA
- davemessina 11y agoHi everyone! Dave Messina from Cofactor Genomics here. I'd be happy to answer any questions you might have. We're excited to launch!
- Asparagirl 11y agoWhat kinds of disorders and diseases will you be testing for? Will your tests be available direct-to-consumer, or will patients have to go through health provider gatekeeping?
- rational-future 11y agoor will patients have to go through evil health provider gatekeeping? FTFY :)
- Asparagirl 11y agoI was trying not to editorialize too much. :-)
- davemessina 11y agoWe are looking at Parkinson's, heart disease, and cancer initially.
- Asparagirl 11y ago...and the gatekeeping?
- lucidrains 11y agoHi, could you point us to some papers on this subject? I have never heard of circular RNAs put into clinical use.
- rational-future 11y agoHey Dave, how does RNA sequencing work for an individual customer? Do you plan to have something like the 23andMe collection kit? In my understanding human cells have may different types of RNA, which one are you sequencing?
- davemessina 11y agoWe plan to offer testing through your doctor, rather than direct to consumer. We are measuring circular RNAs.
- salimmadjd 11y agoCongrats! Co-founder of AsthmaMD here. I'm curious why you are going through doctors and not direct to consumers at the begging? I understand FDA might force you to limit your marketing claims, however you now need to convince both physicians and consumers of the benefits of these tests. No? Where as I would imagine there will be enough early-adopters in the consumer space who'd be happy to pay for a test like this. You can later move to the physicians space and assuringly get insurance companies cover the costs, when you have been more stablished. Would love to learn more about your thinking and strategy here.
- davemessina 11y agoIt's the fastest way for us to get this powerful diagnosis technology on the market and helping people. We believe that our RNA test can become a routine part of a doctor's visit, both as an early indicator of disease and — if there is disease — as a means to monitor the effectiveness of treatment.
- navi54 11y agoWould you ever hire someone from Europe? And what skills do you seek after in a employee?
- daemonk 11y agoBioinformatician here. When you say RNA testing, you mean RNA-seq? Gene expression? If yes, then do you think blood samples will be enough to make these type of diagnosis? I imagine you will probably need tissue specific samples to make some of these disease predictions.
- davemessina 11y agoHi, Great question. We're developing tests around a recently discovered type of RNA called circular RNA. Tissue-specific circular RNAs are present in blood, and so that's how it's possible to use a blood test instead of having to go to tissue like you would with traditional mRNA-seq.
- bhickey 11y agoAre there some key publications you could point us at? I've been out of the bioimformatics game for a couple of years and I'm always curious to see where the state of the art is at.
- davemessina 11y agoHere's a good place to start: http://dx.doi.org/10.1038/cr.2015.82 http://dx.doi.org/10.1038/cr.2015.82
- daemonk 11y agoI don't quite understand how just using circ. RNAs would give you better predictions. From the little I've read about circ. RNAs is that they can form from normal RNAs and possibly function in sequestering regulatory small-RNAs. So you can detect circ. RNA that come from specific tissues and partition those reads out as expression for those tissues? What kind of coverage do you need to do that? Are mRNA circularization rates consistent among different genes?
- jarmstropreamp 11y agoHi daemonk, Jon Armstrong from Cofactor Genomics here. You hit on some excellent points. So you can detect circ. RNA that come from specific tissues and partition those reads out as expression for those tissues? In reality, we are detecting circRNA that arises or predominates during a specific disease state and then partition those reads out as a signal for the disease state. On a related note, the circRNA molecule resists degradation much more than linear RNA molecules, leading to a longer half-life and less variability in signal from tissue, plasma, and exosomes. What kind of coverage do you need to do that? Currently, 100's of million of reads need to be generated to just detect the highest expressed circRNAs. We have a patent pending circRNA enrichment technology (supported by a large NIH phase II grant) that increases the ratio of circRNA in the total RNA pool by logs, thus one could sequence logs less reads for the same level of detection. The coverage cutoff for detection can be "tuned" for assay sensitivity. Are mRNA circularization rates consistent among different genes? CircRNAs do not seem to be translated into proteins and probably perform multiple regulatory functions. Also, the level of a linear form does not correlate with the level of the circular form for the same gene. As with linear mRNA production, which is not consistent from gene to gene or tissue to tissue, we observe the same phenomenon with circRNA. Hope this info helps.
- jonlucc 11y agoIf I find myself in the area, can I take a tour of your lab? I work in pharma and this is interesting to me.
- jarmstropreamp 11y agoJonlucc, Shoot us an email through the website and I am sure we can set something up.
- _ihaque 11y agoHow do circRNA-based biomarkers compare to miRNA-based approaches?
- carbocation 11y agoThe article has a DNA versus RNA spin that, scientifically, is more of a distractor than anything when it comes to cancer. I understand that for marketing, it's useful. In blood cell cancers, Steve McCarroll's group has shown that oncogenic somatic DNA changes are readily discovered through routine sequencing, and these are prognostic of poor outcome.[1] If you do this on a pre-disease schedule based on the risk estimates from your first round of sequencing, you will be able to detect blood cell cancers at any stage you like. In non-blood cell cancers (say, breast cancer), you don't expect to capture any of the tissue-specific cell of interest from a blood draw to determine if there are somatic mutations occurring. However, there is growing evidence that there is often enough circulating tumor DNA in the blood that it can be of diagnostic significance.[2] In contrast, for diseases that do not involve somatic mutations (in other words, for diseases aside from cancer), an RNA-based assay could be quite interesting. For example, getting better characterization around non-dilated cardiomyopathies would be of broad interest. 1 = http://www.nejm.org/doi/full/10.1056/NEJMoa1409405 http://www.nejm.org/doi/full/10.1056/NEJMoa1409405 2 = https://www.genome.gov/27556716 https://www.genome.gov/27556716
- davemessina 11y agoThanks for your comments, and yes, you've got it exactly. In cancer, both DNA and RNA can be effective diagnostics, and there's been a lot of great work on the DNA side in cancer. In essentially all other diseases, though, there are changes in RNA but not in DNA.
- carbocation 11y agoI really think that with heart failure, we need the biomarker equivalent of somatic pre-cancerous DNA changes in cancer. But we also need (to steal from the psychiatrists), better endophenotyping, because many different aberrant states lead to very similar clinical syndromes of "heart failure". A group, perhaps yours or in concert with yours, could both define the disease subsets based on biomarkers and then diagnose/prognose/inform treatment. Surely the same is true for other diseases, this is just one high-impact example.
- jeffdavis 11y ago
- mmaunder 11y agoRelated: Check out Jorge Soto's talk on NPR's Ted Radio Hour: http://www.npr.org/programs/ted-radio-hour/ http://www.npr.org/programs/ted-radio-hour/ Soto is the CTO of Miroculus and they're using MicroRNA analysis to develop a cost effective way to provide early diagnosis for a variety of cancers. So far they've made progress with pancreatic, breast and IIRC two others. This is huge because usually cancer is discovered when you become symptomatic which is usually stage three or worse and it's much harder to treat then. If they can make this cost effective enough to be included in a regular doctor 'check up', then we may catch a large proportion of cancers early which makes treating them way easier.
- robbiep 11y agoSo they're getting 20k from YC to get valley contacts, at the cost of a percentage of the company, when they already have pharmaceutical and NIH funding? Or is there a different deal in place for biotechs?
- davemessina 11y agoOver half of the YC companies (us included) don't really need the money. The $120k investment is only a small part of what YC does. See http://www.ycombinator.com/atyc/ http://www.ycombinator.com/atyc/