Albert Vilella Profile picture
Mar 2, 2021 31 tweets 19 min read Read on X
My highlights of the @10xGenomics #Xperience2021 event. The list of products keeps growing, I would highlight Chromium Connect as an underappreciated tool to bring the products up another level of throughput. Important as with #NGS, it won't take long to go from n=1 to n=96+. Image
#CellPlex species-agnostic multiplexing up to 12 samples: not dissimilar to products such as TotalSeq, but baked-in so that it's been tested to work with the rest of the workflow. Image
Going close to 1M cells, the #ChromiumX brings about 100x fold throughput increase, all marked with 'HT' in the Kits. I'd be interesting to know how the different #BodyAtlas projects embrace this and for what. ImageImage
Now fixed RNA: I am not interested in this (much), but I can see the appeal: store the samples for a few days, make pooling (logistics) easier. Image
Also, pharma companies have shelves upon shelves of tissue slices, so as long as 'old FFPE' works as well as 'recent FFPE', pharma will *love* this: Image
Low-Throughput Gene Expression Kit (1/3 of the cost of standard throughput): very clever move by @10xGenomics, as adoption is always inversely proportional as the barrier to entry of a "failed experiment": can you afford a failed experiment to not dissuade you to try again? Image
A new 5' CRISPR kit: important for applications where 3' does not work. Image
BEAM-T and BEAM-Ab: antigen-specificity, although it doesn't describe how is this done. For BEAM-T, it's based on Tetramer shop peptide synthesis system. Image
BEAM-Ab exemplified for #COVID19 antigen-specificity of 5 different protein probes. This reads to me as "Libra-seq a-la 10X" but no details of the specifics in the presentation. ImageImage
#ChromiumConnect gets more preps available: 5' GEX and immune expression. Smaller prep variability, Hands-on-time, throughput. ImageImage
#Cloud Analysis: who doesn't love the cloud? As some of these analyses are IO heavy and CPU heavy, this facilitates analysis for people without the right infrastructure, but also it's provided *free* for every sample produced. ImageImage
Example of drug screening at different time points, bringing #CellPlex and #ChromiumX: a good way of telling people what kind of experiments they can imagine with these new tools: 96 conditions, 500k cells in 1 HT kit. ImageImage
The second half of the presentation is all about #spatialomics
The #SpatialTranscriptomics acquisition key to improvements by @10xGenomics in #spatialomics (James Chell talking from Stockholm). The #VisiumHD is the biggest announcement, but the FFPE RNA expression Visium is huge for clinical samples.
Good that they acknowledge that the longer the FFPE is in storage, the greater the degradation of the DNA/RNA material. New method starts with high sensitivity. ImageImage
FF vs FFPE correlation plots and pathology annotation correlations with the clustering performed by the #Visium software. Same for IHC. ImageImageImageImage
Initially supported for human and mouse genomes. Image
New configuration of the slides, with large capture areas (2 per slide), with the same resolution as the current ones. Image
Now to the next trick: how to make compatible the samples that are already in slides, and need transferring to the #Visium slides? #CytAssist helps both previewing the tissue sections and select the ones to transfer to #Visium ImageImageImageImage
Loupe Browser Pathology Annotations: manually curated regions to match the pathology-derived reasoning, which then can be interactively turned into biomarkers. ImageImageImage
A network for #Clinical #Translational #Research, including GSK as the biggest pharma partner: Image
Now onto proteins: same tissue section, we can do mRNA, but also proteins: current product allows for a handful of proteins. Now highly multiplexed assay available: 10s of proteins (up to 100?) alongside mRNA. Image
The same sample is thus utilized for mRNA and proteins: no approximations from before/after section.
#VisiumHD: 5um spot size. Images speak for themselves. FFPE compatible. Spots are also tightly packed, so single-cell scale is achieved. All that applies to #Visium does to #VisiumHD now. ImageImageImage
Finally, #ReadCoor and #Cartana acquisitions (Harvard and Stockholm tech, respectively): In Situ platform by @10xGenomics. Nikhil Rao presents. This is for orthogonal approach when you know what you are looking for. Image
Hybridization of probe barcodes directly on tissue, multiple rounds of imaging. No need for #NGS, as it's image-based readout. Showing 1/2 of a mouse brain below, showing oligodendrocytes in blue, single-molecule marks. ImageImage
Combined usage is perceived by @10xGenomics as a great way of deeply studying biology. #singlecell sequencing for discovery, design a targetted panel for in situ, then apply to slides directly. Image
Integrated hardware+software In situ solution coming soon, supporting FFPE and FF. Access program for now. ImageImage
A final remark on the company's segmenting of the market: from research to translational to clinical. They didn't say they want to offer clinical-grade products, but I guess if they could, they would?
All in all, as many have already commented on social media, a very rich presentation from @10xGenomics, which I feel compensates by the lack of oomph by any of the #NGS companies in #AGBT21 so far.
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More from @AlbertVilella

May 18, 2023
The tech update from Oxford @nanopore #NanoporeConf now ongoing with @The__Taybor now presenting:
Duplex: 1.5% of the time, the complement strand follows the first strand naturally.
Initially, modified the adapters and reached 30% duplex rate. Image
Stereo base caller uses similar ML approaches as ChatGPT, Image
Read 9 tweets
May 17, 2023
On library prep at #Nanoporeconf, a description for PCR-free methods showing the difference between ligation (max output) and rapid mode (10minutes, minimal lab equipment needed). Ultralong reads (ULR) also enabled, all Kit14. Image
Rapid ULR. Current record is about 4 megabases. Image
PCR expansion kits enable the use of samples with low input amount. Image
Read 10 tweets
Apr 21, 2023
I did a deep dive on the different workflow management (WFM) tools for #Bioinformatics Data Analysis a few years ago, and since then there have been a few extra entrants in this segment, still mostly concentrated in serving the Next-Generation Sequencing field.
A few years ago, there were two communities dominating the open-source WFM ecosystem in NextFlow and SnakeMake, and two platforms dominating the the commercial offerings in DNAnexus and Illumina BaseSpace.
Since then, a company out of the founders of Nextflow has started offering enterprise support for Nextflow workflows in the cloud: Seqera Labs. They offer the extra level of support that some organizations require to run Nextflow on their Data Analysis setups.
Read 7 tweets
Apr 21, 2023
More interesting Next-Generation Sequencing knowledge in the ASeq Discord channel (by @new299). Illumina patterned flowcells and the etching process to "print" the wells into the flowcell. Could be down to 350nm diameter for some flowcell configurations now. Image
If I remember correctly, Illumina started with a 600nm diameter for the patterned flowcell, in the HiSeq X and then later on in the evolution of the platform that used these patterned flowcells.
They then said to have gone down to 500nm, and what you are showing seems to indicate that it's at 350nm now, at least for the NextSeq 2000? I am not sure if they claimed that for NovaSeq X?
Read 8 tweets
Apr 20, 2023
There have been some acquisitions in #CancerDiagnostics and #CancerScreening recently, some of which signify a trend towards consolidation that is worth describing:
$A Agilent is moving towards some more vertical integration in Cancer Dx and Cancer screening
by recently acquiring both announcing a partnership with Akoya Bio and announcing the acquisition of Avida Biomed. Image
Some may ask: isn’t $A Agilent too small to go into this field? Would they be able to compete against $ILMN Illumina/GrailBio or $GH Guardant Health or $EXAS Exact Sciences?
Read 4 tweets
Apr 20, 2023
It is likely that as Spatial Biology tools become more robust and user-friendly, they will become increasingly popular and widely adopted in the scientific community.
This may lead to a shift in the balance between single-cell and Spatial Biology approaches, with the latter eventually becoming more prevalent.
Additionally, as more and more datasets are generated using Spatial Biology techniques, the field of Machine Learning and Artificial Intelligence will likely play an increasingly important role in analysing and interpreting this data.
Read 6 tweets

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