3 ms·

Original paper [1]: > Here we report the preliminary results of PanSeer, a noninvasive blood test based on circulating tumor DNA methylation... I’m very surpr

Original paper [1]: > Here we report the preliminary results of PanSeer, a noninvasive blood test based on circulating tumor DNA methylation... I’m very surprised that parts of the methylome, the per-cell state-machine that controls what genes are transcribed, have sufficient serum concentration to be detected. I suspect that this approach should work for any diseased cell targeted by the immune system as long as the disease results in a small but unique methylation signature. [1] https://www.nature.com/articles/s41467-020-17316-z https://www.nature.com/articles/s41467-020-17316-z

patall 6y ago
With most of these (cell free DNA) assays, its not a single site that you are measuring but a statistical aggregate about profiles that have been defined for a certain cell type. If you know the overall profile of prostate cells and the profile of normal blood, you can subtract the expected profile from a patient sample and the analyse the left-over fraction for whether it is just noise or is matching to one or multiple known cell types. The surprise from this publication is only that they detect such signatures 4 years earlier than other non-invasive testing. (although nobody in the cfDNA field would be surprised about that).
gww 6y ago
There are newer methods that use antibodies to enrich for methylated dna prior to sequencing [1]. The method increases sensitivity as the majority of plasma cfDNA is unmethylated and hematopoietic in origin. [1] https://www.nature.com/articles/s41586-018-0703-0 https://www.nature.com/articles/s41586-018-0703-0
sradman 6y ago
gww and patall both point out that this is related to cfDNA [1]: > Circulating free DNA (cfDNA) are degraded DNA fragments released to the blood plasma. [1] https://en.wikipedia.org/wiki/Circulating_free_DNA https://en.wikipedia.org/wiki/Circulating_free_DNA

patall 6y ago

With most of these (cell free DNA) assays, its not a single site that you are measuring but a statistical aggregate about profiles that have been defined for a certain cell type. If you know the overall profile of prostate cells and the profile of normal blood, you can subtract the expected profile from a patient sample and the analyse the left-over fraction for whether it is just noise or is matching to one or multiple known cell types. The surprise from this publication is only that they detect such signatures 4 years earlier than other non-invasive testing. (although nobody in the cfDNA field would be surprised about that).

gww 6y ago

There are newer methods that use antibodies to enrich for methylated dna prior to sequencing [1]. The method increases sensitivity as the majority of plasma cfDNA is unmethylated and hematopoietic in origin. [1] https://www.nature.com/articles/s41586-018-0703-0 https://www.nature.com/articles/s41586-018-0703-0

sradman 6y ago

gww and patall both point out that this is related to cfDNA [1]: > Circulating free DNA (cfDNA) are degraded DNA fragments released to the blood plasma. [1] https://en.wikipedia.org/wiki/Circulating_free_DNA https://en.wikipedia.org/wiki/Circulating_free_DNA