Clincal Questions

I was talking about clinical markets again today and realized it might be useful to pull together and summarize my previous notes so here goes.

Sample-to-Answer Sequencing

What would you need to do to build a sample-to-answer system, like we have in qPCR but with sequencing? Notes on a Cepheid of Sequencing here.

A sample prep approach for infectious disease testing. Oxford Nanopore’s sample to answer patent.

Rapid NICU Sequencing

My notes here. A fundamentally important idea, which I’m strongly in favor of. Where I couldn’t get the numbers to work as a startup pitch. Fundamental problem, only 10% of current cases with a suspected genetic cause get any genetic testing anyway. You need to expand that to near 100% to have a sufficiently large market to attract investors. That seems like a hard sell, particular as many of those cases may be things like cleft lips where there is a genetic contribution, but identifying it is unlikely to change care opinions.

Clinical Sequencing Market Breakdown

My notes here on breaking down Illumina’s $2B clinical market. Which is “~25% NIPT, ~25% genetic disease testing (GDT) and 50% oncology”. Mostly applications where are currently well served by Illumina style, long time to answer short reads and would benefit little from new approaches which may need to look elsewhere to expand the market?

Except for perhaps oncology?

Sequencing For Oncology

My notes here as part of breaking down Illumina’s $1B oncology market. My guess: “no one segment of MRD, Therapy Selection and Germline goes over 50% of revenue for Illumina. You might expect that Germline testing (things like BRCA tests) is largest, then therapy selection then MRD.”

Again, probably all markets well served by Illumina? So new approaches would need to seek to expand elsewhere in oncology?

My notes on GRAILs cfDNA paper, and cfRNA paper.

Why I Sometimes Get Depressed Thinking About Clinical Sequencing

My notes on my I love clinical sequencing and why it doesn’t get used as much as it perhaps should (yet). That case of Malaria in Maryland, which helps me calibrate my thinking on how testing is used in practice. My experiences with clinicians who don’t want to perform genetic tests for intellectual disability.

Infectious Disease Testing

Reticula: Why we should do metagenomic sequencing based infectious diagnostics testing for pandemic preparedness. A technological approach that might work.

Sequencing is more sensitive than qPCR. My initial assertion that sequencing is more sensitive than qPCR. A review showing that sequencing is more sensitive than qPCR, a model showing sequencing is more sensitive than qPCR.

An analysis showing that you only need very short reads for infectious disease testing. A discussion of one paper in this area. A write up on the utility of long reads for infectious disease testing.

Arguments against metagenomics based infectious disease testing, basically boils down to “people quite like qPCR actually”. It’s cheap, they get to charge high margins, it’s targeted. Gives them the answer they’re looking for.

A case of Malaria in Maryland, where they didn’t do test and then ignored tests, until they finally decided to change treatment.

Thoughts on sample prep for clinical apps.

Other Things

A very quick look at repeat expansions using long reads. Playing looking at some theoretical questions on the utility of long reads. Sex selection technologies.