Thread by @sbarnettARK

The widespread adoption of liquid biopsy seems to be 'un-commoditizing' DNA synthesis in the molecular diagnostics industry.

Recall that synthetic DNA probes, molecules that bind and pull a DNA out of solution, are a critical input for liquid biopsy.

Diagnostics companies buy probes to use in their clinical tests, oftentimes in bulk, from a synthetic DNA provider. There's been a prevailing notion recently that DNA providers only can differentiate on the basis of cost or turnaround time.

I think liquid biopsy changes this.

Firstly, a huge technical constraint in liquid biopsy is the availability of cancerous DNA in a tube of blood, which decreases exponentially with tumor size.

Remember that smaller tumors don't leak as much DNA into the bloodstream.

Sequencing can be a lossy process.

It doesn't matter how deeply you sequence if you don't have cancerous DNA to start with. There may be only ~10 copies of the genome in a tube of blood. Shipping, isolation, extraction, amplification, methylation conversion, all these steps carry risk of destroying the DNA.

So, this is placing a huge premium on capture efficiency and uniformity - basically how good synthetic DNA probes bind and pull out of solution what you want to sequence versus what you don't. At scale, this can result in massive improvements in operating efficiency.

So, beyond just cost and turnaround time, uniformity and efficiency come into play. Remember that diagnostics companies also devote lab space to design/build/test cycles for new tests, so turnaround time gets even more important.

Now let's talk about multi-omics.

With earlier cancer detection, labs 'stack signals' by building diagnostics that input multi-dimensional biological data - say DNA mutations, DNA fragment patterns, epigenetic signatures (5mC, 5hmC), cell-free RNA, and whose to say we won't keep adding more?

Stacking orthogonal data steams can turn a faint cancer signal into a loud one, making it easier to detect even in early stages.

Each of these buckets of data is another sample prep obstacle (or opportunity?) for SynBio vendors.

For example, methylation conversion alters sequence complexity and may cause probes to be blocked from binding to their targets, necessitating more sophisticated probe design and another avenue for differentiation.

Diagnostics companies are becoming hyper-competitive.

I think the market for differentiation NGS capture/conversion/sample prep solutions will grow as liquid biopsy grows. Many new companies will come to the table and the long tail of dedicated researchers will want to contribute to our collective knowledge as well.