How do circRNA-based biomarkers compare to miRNA-based approaches?
Cofactor Genomics (YC S15) Pursues RNA Testing, Offers Better Diagnoses Than DNA
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Re: Cofactor Genomics (YC S15) Pursues RNA Testing, Offers Better Diagnoses Than DNA
#22Hi everyone! Dave Messina from Cofactor Genomics here. I'd be happy to answer any questions you might have. We're excited to launch!
Congrats! 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.
Re: Cofactor Genomics (YC S15) Pursues RNA Testing, Offers Better Diagnoses Than DNA
#23Hi everyone! Dave Messina from Cofactor Genomics here. I'd be happy to answer any questions you might have. We're excited to launch!
Congrats! 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.…
It'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.
Re: Cofactor Genomics (YC S15) Pursues RNA Testing, Offers Better Diagnoses Than DNA
#24Earlier quoted context omitted.
I 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 circularizati…
Hi 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 r…
Finally a topic on hackernews that I am getting my PhD in..! Anyway, do you have any data indicating what percentage of circRNA is "free" in the plasma versus inside of other entities like platelets or extracellular vesicles (exosomes)?
Re: Cofactor Genomics (YC S15) Pursues RNA Testing, Offers Better Diagnoses Than DNA
#25Bioinformatician 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.
Hi, 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.
Circular RNAs are really "hot" these days. But, one should keep in mind that the amount of virtually all circular RNAs is lower in cancer (compared to non-cancerous adjacent normal tissue), thus they are not very promising as biomarkers. Also, their biological role is unclear. We did comprehensive literature review on this topic and found nothing truly convincing.
Re: Cofactor Genomics (YC S15) Pursues RNA Testing, Offers Better Diagnoses Than DNA
#26Earlier quoted context omitted.
Hi, 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.
Circular RNAs are really "hot" these days. But, one should keep in mind that the amount of virtually all circular RNAs is lower in cancer (compared to non-cancerous adjacent normal tissue), thus they are not very promising as biomarkers. Also, their biological role is unclear. We did comprehensive literature review on this topic and found nothing truly convincing.
That some circRNAs are lower in cancer than in normal tissue is a reliably detectable difference and is precisely what makes them an excellent biomarker.
There's additional evidence shown here: "Using circular RNA as a novel type of biomarker in the screening of gastric cancer". http://dx.doi.org/10.1016/j.cca.2015.02.018
Re: Cofactor Genomics (YC S15) Pursues RNA Testing, Offers Better Diagnoses Than DNA
#27Earlier quoted context omitted.
Circular RNAs are really "hot" these days. But, one should keep in mind that the amount of virtually all circular RNAs is lower in cancer (compared to non-cancerous adjacent normal tissue), thus they are not very promising as biomarkers. Also, their biological role is unclear. We did comprehensive literature review on this topic and found nothing truly convincing.
That some circRNAs are lower in cancer than in normal tissue is a reliably detectable difference and is precisely what makes them an excellent biomarker. There's additional evidence shown here: "Using circular RNA as a novel type of biomarker in the screening of gastric cancer". http://dx.doi.org/10.1016/j.cca.2015.02.018
I am aware of this study. Funny, how they show expression in deltaCT to make it appear higher in cancer ;). But regardless, the marker has a specificity of 0.62 - really that excellent? Such a high false-positive rate does not belong anywhere near a patient sample.
Re: Cofactor Genomics (YC S15) Pursues RNA Testing, Offers Better Diagnoses Than DNA
#28The 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.
Re: Cofactor Genomics (YC S15) Pursues RNA Testing, Offers Better Diagnoses Than DNA
#29The 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 esti…
Thanks 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.
Re: Cofactor Genomics (YC S15) Pursues RNA Testing, Offers Better Diagnoses Than DNA
#30The 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 esti…
Thanks 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.
I 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.