All fair enough. The two big immediate challenges in the field are i) that the tumor-derived fraction of total cfDNA can be as low as 1:10000 (stage I) and ii) that it is difficult to make Illumina sequencing more accurate than 1 error in 1000 sequenced bases (in which case the 1:10000 signal is drowned out). This paper uses some clever statistical tricks to reduce Illimina sequencing error; one of these tricks is to leverage population information, i.e. the more samples you sequence the better your understanding of (non-cancer-associated) systematic errors. This follows a long tradition in statistical genetics of using multi-sample panels to improve analysis of individual samples. There are also biochemical approaches like SafeSeq or Duplex Sequencing to reduce sequencing error.
Not-so-obvious point #1 is that the presence of cancer-associated mutations in blood != cancer. You find cancer-associated mutations in the skin of older probands, and assumedly many of the sampling sites would never turn into melanomas. A more subtle point is that cfDNA is likely generated by dying cells, i.e. a weak cancer signature in blood might also be indicative of the immune system doing its job.
Point #2 is that it's not necessarily about individual mutations, which are, due to the signal-to-noise ratio alluded to above, difficult to pick up. One can also look at the total representation of certain genes in cfDNA (many cancers have gene amplifications or deletions, which are easier to pick up because they affect thousands of bases at the same time), and the positioning of individual sequenced molecules relative to the reference genome. It seems that these positions are correlated with gene activities (transcription) in the cells that the cfDNA comes from, and cancer cells have distinct patterns if gene activity.
There is also Freenome, which raised a $65m Series A to bring something similar to market:
> Last year, we raised $5.5 million to prove out the potential of this technology. Now, it’s time to make sure that it’s safe and ready for the broader population.
https://medium.com/freenome-stories/freenome-raises-65m-in-s...
I haven't read the referenced study, but I'm sure this is using the same (or very similar) cell free DNA (cfDNA) sequencing techniques currently used clinically for Non Invasive Prenatal Testing (NIPT) to screen for genetic defects such as trisomy 21 (Down Syndrome).
NIPT is a non-invasive blood screening test that is quickly becoming the clinical standard of care. Many insurance companies now cover the entire cost of NIPT screening for for at-risk pregnancies (e.g. women of "Advanced Maternal Age" (35yo+)). The debate is moving to whether it should be utilized/covered for average-risk pregnancies as well.
[1] http://capsprenatal.com/about-nipt/
[2] https://www.genomeweb.com/molecular-diagnostics/aetna-wont-c...
Slowly but surely. This isn't even close to a real diagnostic, but it's a hopeful proof of concept.
I really do wish detection studies would publish a ROC curve, though, or at least d'.
Possibly a silly question, but is it possible for a 'healthy' person who doesn't have any cancer risk factors to get a test like this done?
According to Craig Venter, early detection is what we need to eliminate cancer:
https://youtu.be/iUqgTYbkHP8?t=15m37s
I guess most are treatable if caught early?
Didn't Grail raise a billion dollars to do just this?
> They found none of the cancer-derived mutations among blood samples of 44 healthy individuals.
Is 98% specificity adequate for a cancer test?
When this test has a near 100% success rate, how does it help the patients? Can it really prevent cancer?
Tangent: I'm invested in a small cap stock, Sophoris Bio, that's in a P2B study for prostrate cancer with a drug developed out of Johns Hopkins called PRX302 (Topsalysin).
That and the article about blood tests shows there's a lot they're working on for noninvasive or minimally invasive procedures to help prevent cancer early on.
I work for another player Guardant Health. We are the Liquid Biopsy market leaders right now. We just raised $360M Series E from SoftBank.
If you find this type of thing interesting and want to be part of it, we are hiring lots of folks. My team is looking for bioinformaticians, Python hackers, and machine learning people. Please reach out to me if you want to know more jgourneau@guardanthealth.com