@MJLBio@Sanctuary_Bio@Biohazard3737 Sure! I realize I was being a little vague with those statements. Generally, I think you're correct in your interpretation of the importance of P2 (great $/GB, but at a smaller scale) as well as duplex sequencing.
Something that is important to recognize, though ...
@MJLBio@Sanctuary_Bio@Biohazard3737 ... is how product deployment works differently between PacBio and Nanopore, which is partly an artefact of culture and of time in the public markets, in the public markets. I'm not advocating for one over the other with my next statements.
@MJLBio@Sanctuary_Bio@Biohazard3737 PacBio has been a public company for a long time. While the management has changed much since the failed Illumina merger, the familiarity with how to operate as a public company has not.
PacBio is more secretive and only unveils fully built-out commercial products.
Nanopore has a very transparent, quick-turn deployment schedule that is all out in the open. The improvements are visible/incremental, which is a great value proposition for its customers.
I'd like to share my initial reaction to today's Berkeley Lights report. But first, I need to do some housekeeping. I can't comment on stock movements, share financial projections, or debate fair value.
Generally, I respect anyone who's put this much work into a topic. I won't pretend to have a clean rebuttal to every point. In my experience, beyond the hyperbole and hasty generalizations, there is some truth in these types of reports.
I want to soberly appraise those truths.
Also, I'd invite the subject-matter experts waiting in the wings to build off of this thread, add detail, or share their experiences. Ultimately, we're all after the same thing.
I will start with a few concessions and end with a few counterpoints to today's report:
Imagine that a meteor was hurtling through space towards the Earth. Its speed and trajectory indicate that it will destroy the planet in approximately 10 years.
Now, let's say that our best sensors are only ...
... capable of seeing said meteor 1 year in advance. So, 9 years go by and we are blissfully unaware of our impending doom. Then, at the 9-year mark, we detect the meteor and measure our remaining survival time to be just 1 year.
What if I gave you a better sensor? What if this sensor could see the meteor from 10 years away instead of just 1?
How long would our survival time be? While we may have a 10-year lead time instead of a 1-year lead time, the meteor still strikes us on the same day.
As short-read #sequencing (SRS) costs begin to drop again, undoubtedly fueled by a resurgence in competition, I suspect many liquid biopsy providers will add blood-based whole-genome sequencing (WGS) to supplement, or replace, the deep targeted sequencing paradigm.
With a few exceptions, most clinical-stage diagnostic companies build patient-specific panels by sequencing the solid tumor, then downselecting to a few dozen mutations to survey in the bloodstream.
I don't think this approach is going anywhere anytime soon.
However useful, this deep-sequencing approach suffers from several challenges:
1. It requires access to tissue. 2. It requires the construction of patient-specific PCR panels. 3. It requires significant over-sequencing ($$$). 4. It introduces a third layer of error (PCR).
We often discuss how more comprehensive and sensitive techniques improve the diagnostic yield for patients affected by rare genetic diseases. Indeed, yields have improved as we've gone from microarrays to whole genome #sequencing.
However, there's another critical component.
Case-Level Reanalysis (CLR)
By reanalyzing genomic data, as our global knowledge-base grows, we improve diagnostic yields.
We believe the broadest tests should be done first to avoid the need to re-contact and re-accession patient samples.
The economics for both the lab (and patient) change dramatically as well in a 'generate-once-reassess-often' framework. As more is known, variant interpretation may shift from being more manual to more automated.
Still, this is a really hard technological problem.
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.
@NatHarooni@snicobio I’m watching Jeopardy—will come back later tonight. Short answer—no, not competitive to PacBio. Likely friends down the road.
@NatHarooni@snicobio Alright, so in theory the QSI platform can enable DNA (or RNA) sequencing on chip. However, I think of it more like a call option and less of a near-term goal. Proteomics is the killer app enabled by the QSI platform. But, as OP alluded to, multi-omics (inc. proteins) on one ...
@NatHarooni@snicobio ... instrument could be an attractive value prop. from a capital outlay point of view, especially for $50K which is achievable for many labs w/o needing to seek a major grant (so speedy sales cycles). Now, back to the main point about sequencing. If you read the patents ...