A Diagnostic Sequencing Roadmap

I’ve been working on a report on clinical diagnostic sequencing (focused on pandemic preparedness) for a philanthropic organization. If you’d like a copy get in touch (new@sgenomics.org), we’ve been looking for reviewers.

The main idea is to develop a sequencing platform that could displace qPCR.

Individuals with suspected infections would be be diagnosed through meta-genomic sequencing, which would provide a full respiratory panel, as well as detection currently unknown viruses.

The platform therefore needs to be as fast, as cheap, as sensitive, and as accurate as qPCR, in addition to providing all the benefits of sequencing.

In terms of what sequencing technology this approach should use, I personally remain convinced that a single molecule optical approach is one of the only routes to an ultra-low cost per sample platform. The other viable approach might be a cost optimized nanopore platform. But I don’t think this will come from Oxford Nanopore…

However one of interesting things to come out of this report, is how easy it would be to build a cheap ($2 COGS, sold for $10?) meta-genomic sample prep system. This would take a meta-genomic sample (nasal swab) and perform extraction, cDNA synthesis and library preparation. This could then be thrown onto an existing sequencer (MiSeq).

Current automated sample prep platforms have all been designed for heterogeneous workloads where they can be user reconfigured to address different applications.

But, what we’re suggesting would be a cost-optimized cartridge which looks much more like a GeneXpert cartridge than a complex pipette robot or digital microfluidics platform.

This is something we could build today (if anyone has $1M and would like to help build this get in touch :)). And it would be immediately useful to a number of users. Allowing respiratory (or other) sample to be diagnosed in < 8h, providing a full respiratory panel, and a full meta-genomic diagnostic for <$1000 and with minimal technician time.

Such a platform would likely only be viable for samples which have no clear diagnosis which a first stage diagnostic (either qPCR or a panel). But, this could be the first step in a roadmap to a much cheaper device which could displace qPCR:

Here, you would start by working with groups already doing meta-genomic sequencing on samples that have failed be diagnosed using existing approaches. This would provide an immediate benefit and allow them to expand their efforts (which are likely somewhat limited by technician time).

Building on this you could expand to make instruments incorporating sequencing, and which could be placed directly in hospitals and clinics. And finally, iterate on the platform reducing the instrument and consumable cost until it just doesn’t make sense to use qPCR at all any more.

Why am I so focused on killed qPCR? Because I think that’s the only way we can build a platform that makes us robust to future pandemics.

A first diagnostic which uses meta-genomic sequencing allows us to detect future pandemic capable viruses early and gives us the opportunity to prevent their spread.