Tweet

Simon Barnett

11 Mar, 10 tweets, 7 min read

@NatHarooni

@NatHarooni @snicobio I’m watching Jeopardy—will come back later tonight. Short answer—no, not competitive to PacBio. Likely friends down the road.

@NatHarooni

@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

@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 ...

@NatHarooni

@NatHarooni @snicobio ... you'll notice that QSI's detection method is similar to PacBio's zero-mode waveguide (ZMW) and dissimilar from Illumina's, which uses clusters and amplification and not single-molecule chemistry (QSI and PacBio share this). So, my guess is that if PacBio wanted to ...

@NatHarooni

@NatHarooni @snicobio ... they could allow their chemistry to be readout on a QSI detector to speed the proliferation of HiFi chemistry. Illumina could do the same, but I'm skeptical they would and I'm not sure the pieces would fit (Tool pun) as well as QSI <> PacBio because of the similarities ...

@NatHarooni

@NatHarooni @snicobio ... between SMRT and QSI library prep, which could both be enabled on QSI's universal library prep instrument. Enabling a HiFi readout on a QSI platform would also help QSI (is my guess) because they can push more instruments. Note that QSI's detection method ...

@NatHarooni

@NatHarooni @snicobio ... is optical, not based on fluctuations in current across a channel -- so you couldn't run a nanopore library on a QSI system is my guess. I think QSI (in a year or a few) could allow DNA seq companies to run their libraries on QSI systems (good for everybody). Finally, if ...

@NatHarooni

@NatHarooni @snicobio ... you look at QSI's pitch deck, the image for DNA seq is literally exactly what's happening inside a PacBio instrument -- anchor a polymerase and feed a circularized DNA loop to get a consensus read from a single, long molecule. Now, you could ask why QSI ...

@NatHarooni

@NatHarooni @snicobio ... doesn't just do their own DNA seq on its own instruments, and I would remind folks that doing sequencing to the level of HiFi is REALLY hard and involves way more molecular engineering than just a good detector. QSI's IP (aptamers, etc) is for proteins, not DNA.

@NatHarooni

@NatHarooni @snicobio Also, this was a very good/interesting thread @snicobio, and thanks @NatHarooni for tagging me into it

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More from @sbarnettARK

Simon Barnett

@sbarnettARK

22 Feb

@NatHarooni

@NatHarooni @AlbertVilella In my opinion — HiFi reads are the most accurate/complete, but currently are more expensive and lower throughput. Nanopore reads are cheap, fast, and high-throughput, but have a weaker error profile. Both of these descriptors are changing and may not be the case in a few years.

@NatHarooni

@NatHarooni @AlbertVilella As far as QSI is concerned, it’s a little too early for me to calculate operating costs per run. I’ll update when I know more.

@NatHarooni

@NatHarooni @AlbertVilella Regardless of how you consider the remaining engineering obstacles, necessary R&D spend, or computational issues—I feel that long-read sequencing (as a class of tech), will outperform short reads on virtually every relevant metric by 2024-2025

Read 4 tweets

Simon Barnett

@sbarnettARK

21 Feb

@nhawk45

@nhawk45 @AlbertVilella Hey, @nhawk45 -- Sure, I think I can take some of these. Let's start from the beginning to help explain why certain features of QSI's approach/IP are needed and interesting.

First: Why are proteins the hardest molecules to sequence of the 'big three'? (DNA/RNA/Proteins) ...

@nhawk45

@nhawk45 @AlbertVilella Here are some of my notes on reasons I could think of, but I'll take a moment to elaborate on some of them.

The proteome is estimated to have the largest 'unit diversity' for lack of a better term. DNA = 20K genes, RNA = 10^5 isoforms, proteins = 10^6 proteofroms ...

@nhawk45

@nhawk45 @AlbertVilella Proteomic diversity is driven by post-translational modifications (PTM), which is a set of chemical alterations to peptides not dissimilar to how DNA can have #epigenetic modifications like methylation. Combine this w/ the fact that peptides have a 20-letter alphabet ...

Read 7 tweets

Simon Barnett

@sbarnettARK

18 Feb

Anyone have any opinions on how self-insured employers consider innovative healthcare offerings to pass on to their employees?

As I understand it, by shouldering the financial risk, self-insured employers can curate a list of more relevant benefits ... (1/10)

... thereby avoiding paying out lofty insurance premiums for services that its employees don't use or want. There seems to be a long list of intangible benefits having to do with talent acquisition and retention, but I'd like to understand the cost equations more fully. (2/10)

In the context of multi-cancer screening, I'm skeptical that it could be cost-saving for small or medium-sized employers (<500 employees). Assuming a representative sample of the population, there are simply too few cancers and too many false positives w/ expensive ... (3/10)

Read 11 tweets

Simon Barnett

@sbarnettARK

17 Feb

@TerraPharma1

@TerraPharma1 @hiddensmallcaps Apologies for the incoming Tweet storm . . .

@TerraPharma1

@TerraPharma1 @hiddensmallcaps Here are some of my thoughts on the Personalis <> Natera tie-up. This is mostly a tech-focused breakdown, so not a recommendation to buy, sell, or hold any security: (bit.do/eyRo8)

First, a bit of background on the details and opinions scattered throughout . . .

@TerraPharma1

@TerraPharma1 @hiddensmallcaps Historically, Personalis has focused entirely on serving the biopharma market. These customers aren't as price-sensitive and they have an insatiable appetite for novel discoveries. In our view, Personalis' NeXT platform is a great biopharma product-market fit. Why? . . .

Read 17 tweets

Simon Barnett

@sbarnettARK

17 Feb

As cash-rich molecular diagnostics companies scale volume and expand menu breadth, there could be an "acqui-hire" shockwave.

These growing companies likely will continue vertically integrating in front (sample prep) and behind (informatics) to gain . . . (1/4)

. . . operating efficiencies on the move up. Or, there could be a weak link in the existing R&D pipeline that needs mending all-of-a-sudden. For example, that extracting bite-size #epigenetic signal from blood would be central to earlier #cancer detection . . . (2/4)

. . . maybe wasn't as obvious five years ago. There seems to be a ton of awesome IP/university spinouts that've gone on to become private companies and/or patents. Along with this, a fleet of brilliant scientists/impassioned people who . . . (3/4)

Read 4 tweets

Simon Barnett

@sbarnettARK

16 Feb

@TGen

Interesting that Exact acquired Ashion (private) ostensibly to bring tumor-normal profiling onto the platform. This comes after they got exclusive rights to the TARDIS platform for MRD testing. Both Ashion and TARDIS come out of @TGen, so likely a smoother integration.

Here's the original TARDIS paper: tgen.org/news/2019/augu…

Seems to be another form of error-corrected sequencing, which is useful for liquid biopsy applications where tumor fraction (amount of cancer in body) is very low, so this reads through to mutation-based early ...

... detection assays (CancerSEEK) as well as for MRD, where tumor burden is low, but more emphasis on dynamics of the tumor (treatment resistance, clonal evolution, etc) in addition to just quantification of the tumor (ctDNA % up or down).

Read 6 tweets

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