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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

#11

Post by bhickey »

davemessina wrote: post #7
daemonk wrote: post #4

Bioinformatician 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.

Are 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.

Re: Cofactor Genomics (YC S15) Pursues RNA Testing, Offers Better Diagnoses Than DNA

#12

Post by lucidrains »

davemessina wrote: post #10
Asparagirl wrote: post #3

Earlier quoted context omitted.

What 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?

We are looking at Parkinson's, heart disease, and cancer initially.

Hi, could you point us to some papers on this subject? I have never heard of circular RNAs put into clinical use.

Re: Cofactor Genomics (YC S15) Pursues RNA Testing, Offers Better Diagnoses Than DNA

#13

Post by daemonk »

davemessina wrote: post #7
daemonk wrote: post #4

Bioinformatician 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.

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 circularization rates consistent among different genes?

Re: Cofactor Genomics (YC S15) Pursues RNA Testing, Offers Better Diagnoses Than DNA

#14

Post by davemessina »

bhickey wrote: post #11
davemessina wrote: post #7

Earlier 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.

Are 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.

Here's a good place to start: http://dx.doi.org/10.1038/cr.2015.82

Re: Cofactor Genomics (YC S15) Pursues RNA Testing, Offers Better Diagnoses Than DNA

#16

Post by danieltillett »

davemessina wrote: post #7
daemonk wrote: post #4

Bioinformatician 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.

Dave what is the patent landscape like for circular RNA? I hope it is better than RNAi or antisense?

Re: Cofactor Genomics (YC S15) Pursues RNA Testing, Offers Better Diagnoses Than DNA

#17

Post by davemessina »

danieltillett wrote: post #16
davemessina wrote: post #7

Earlier 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.

Dave what is the patent landscape like for circular RNA? I hope it is better than RNAi or antisense?

Hi Daniel,

We've filed patents on our work.

Is there any biotech patent landscape as bad as RNAi? :)

Re: Cofactor Genomics (YC S15) Pursues RNA Testing, Offers Better Diagnoses Than DNA

#18

Post by jarmstropreamp »

daemonk wrote: post #13
davemessina wrote: post #7

Earlier 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.

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 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.

Re: Cofactor Genomics (YC S15) Pursues RNA Testing, Offers Better Diagnoses Than DNA

#19

Post by Asparagirl »

davemessina wrote: post #10
Asparagirl wrote: post #3

Earlier quoted context omitted.

What 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?

We are looking at Parkinson's, heart disease, and cancer initially.

...and the gatekeeping?
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