Reviewing the Oxford @nanopore presentation now available to replay. Two highlights/thoughts that I didn't tweet about before:
1) Spike-in for re-training
2) Strand-specific DNA modifications
1) Looking at the kind of stuff presented, where temperature settings, salt, etc. are being more available to end-users, there is an opportunity here to retrain models and improve basecalling for specific datasets.
On a much simpler level, Illumina sequencer did and still do some of that: one would need to spike-in a certain amount of PhiX for the machine to calibrate itself. For low-complexity applications, like 16S sequencing, this could be as high as 25-50% of the reads/throughput.
Even though not explicitly mentioned by @The__Taybor in the latest presentation (as of 2022-04-08), this maybe something to think about: spike-in certain known sequences, and together with the measured temperature/salts/etc of the run, then use that to re-train the models and ...
... then basecall at higher accuracy. One of my obsessions with #NGS is #epigenomics, and thus improvements on accuracy of 5mC/5hmC/5fC/etc are in my opinion move the needle forward in #LiquidBiopsy and other important applications.
2) Strand-specific base modifications:
Even though Oxford @nanopore has already surpassed bisulfite sequencing with their 5mC base calling, there is another aspect of this that I want to highlight.
The fact that Duplex calling of base modifications works on the basis of a non-PCRed molecule (double-stranded DNA), one guarantees that both strands came directly from the sample, thus when sequencing both strands and calling base modifications...
... the modified bases are naturally strand-specific. This can have important applications, as the order and tempo with which the base modifier enzymes perform inside the cells matters in understanding cell states.
Now, even though there are lots of scientific publications on strand-specific base modifications and their link to cell biology and cell development, I think the field is not as mature in diagnostics as it is for the non-strand specific use of #epigenomics for diagnostics.
Unless someone with more knowledge can correct me, applications such as the ones GrailBio and Guardant Health are using are non-strand specific, either by design or by technology limitation. And none of them uses yet a combination of 5mC / 5hmC, which relate to each other.
And here is where I think there is an opportunity for either Oxford @nanopore or adaptations of current methods using short-read 4-base sequencing to do both profiling of 5mC + 5hmC but adding the strand-specific readout that comes naturally from nanopore Duplex reading.
Still something to mull on further, but I believe that the signal is there to be mined.

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More from @AlbertVilella

Apr 6
In #biotech #stock news, I've added $NSTG NanoString to the list of companies I follow, one of the players in the single cell and spatial omics fields Image
The field is still dominated by $TXG 10X Genomics, which also have recently acquired 3 different companies in the spatial omics area, which encapsulate 60-70% of the technologies used for all the papers published using such technologies. Image
You can read more about the history of the field and current players and trends in this document produced by @LambdaMoses : pachterlab.github.io/LP_2021/index.…
Read 4 tweets
Mar 19
Recap on #NGS after the @ElemBio #AVITI instrument release. Who are the main players in NGS?
Illumina remains the market leader with the short-read SBS technology. They segment their products into high-throughput (NovaSeq $1M), mid-throughput (NextSeq $220-350K) and low-throughput (MiSeq, MiniSeq, iSeq $40-150K).
Then there are to large players, but smaller to Illumina in comparison, in the long-reads field: Oxford Nanopore, with their MinION, PromethION and other modes of sequencing, and PacBio, with their Sequel2 instrument, but with a future play on short-reads with Omnione.
Read 18 tweets
Mar 14
Element Bio (@elembio) is announcing their first instrument today. I'll concentrate on my own highlights on the presentation, which I am sure it'll be available as a video later on.
My professional interest on the announcement today is: could this be a replacement to a mid-throughput instrument like the NextSeq 2000/1000? If the price in the first specs slide is right, I think the answer is yes!
The Challenge -- Decrease Cost/Gbp without requiring ultra-high throughput
Read 30 tweets
Feb 20
Quick history of @10xGenomics products:
=== Linked-Reads Chromium Genome and Exome ===
10x Genomics started as a company by selling instruments and reagents for their Linked-Reads method to generate long synthetic DNA reads out of short-read readouts such as those from Illumina SBS sequencers.
These Linked-Reads were useful for de novo genome assembly applications, where the length of the reads is crucial to produce long assembled sequences. As of June 30, 2020, the company discontinued the sale of the Chromium Genome and Exome product lines.
Read 13 tweets
Jan 23
Those who follow my account for a while will already know that I've been following the field of Next Generation Sequencing for many years now, and I keep a series of resources comparing different platforms and technologies.
Beyond the first tier of 4-5 large NGS companies out there, such as Illumina, PacBio, Oxford Nanopore, Thermo's Ion Torrents and MGI Tech, there is now a growing group of small companies pinning for an NGS market which is growing and maturing in many ways.
I keep a table comparing these companies, with around 40 different ones, although some of them have a small chance of making it into the market, and they may be acquired by someone else to expand their technological capabilities. bit.ly/nngseq
Read 10 tweets
Jan 14
One more from #JPM22, maybe the last one from me: PacBio's presentation which took place on the 13th January. Intro slide about the company. Image
There are now 374 Sequel II/IIe machines installed, the company's revenue is growing and is in the triple digit annually. Image
The number of SMRT Cells shipped has almost doubled since 2020, quadrupled since 2019. That's a good sign for PacBio. Image
Read 25 tweets

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