In #NextGenerationProteomics news, today we cover the basics of Proximity ligation assay (PLA) technology, also known as proximity barcoding assay technology, which is a method for detecting protein-protein interactions in cells or tissues.
The assay is based on the principle of ligating two probes (such as antibodies) that are in close proximity to each other, typically within a few nanometers. The ligation reaction produces a circular DNA molecule that is amplified by polymerase chain reaction (PCR) and
can be detected by sequencing or by fluorescence-based microarray readouts. The technology allows for the quantification of specific protein interactions in complex biological samples and can be used for a variety of applications, including drug discovery,
protein biomarker validation, and protein expression analysis. An example use of the technology can be that of a case/control proteomics analysis:
A case/control analysis of protein presence and abundance involves comparing the levels of specific proteins between two groups: a "case" group, which represents individuals with a particular disease or condition of interest, and a "control" group, which represents individuals
without the disease or condition. The goal of this analysis is to determine if there is a significant difference in the levels of specific proteins between the two groups.
For example, let's say that a researcher is interested in studying the presence and abundance of a protein (protein X) that is believed to be involved in the development of a particular type of cancer. The researcher collects tissue samples from a group of individuals with
the cancer (the case group) and a group of healthy individuals (the control group). The samples are then subjected to a proteomics analysis to determine the levels of protein X in each sample.
The results of the assay are then analyzed to compare the levels of protein X between the two groups. If there is a significant difference in the levels of protein X between the two groups, this suggests that the protein may play a role in the development of the cancer.
On the other hand, if there is no significant difference, this suggests that the protein is unlikely to play a role in the development of the cancer. This type of case/control analysis can be used to gain insights into the presence and abundance of specific proteins in
various diseases and conditions, and can inform the development of new diagnostic tests and treatments. Extending the reasoning of the analysis of "protein X" to a group of proteins, for example, 100 different proteins, or 1000, or 7,500, with an NGS readout, is what $OLK Olink
is doing in the field of next-generation proteomics.
Sensitivity via a two-mAb system is one of the advantages of the Olink method. The disadvantage is that it is limited to the probes that have been designed, so it's not a de novo discovery tool.
The method is currently limited to how many probes can be added to a panel. Larger panels will grow the TAM for these type of technologies. So if Olink is capable of execution into both larger panels and its commercial reach, they have a bright future ahead of them.
Olink is not the only player in this new wave of proteomics assays, and others apply similar methodologies to them, with small differences, like SomaLogic. Other technologies, such as the ones from Seer, Nautilus Bio, Quaterix, MesoScale or Luminex are offering equivalent
methods that either have different depth (number of samples/proteins) or amplitude (log-scales of quantitation).
Finally, companies such as Quantum-SI are doing de novo protein sequencing, which means they can be used as a discovery tool, rather than based on panels.
Erisyon and Encodia can also be put in a similar bucket by a broad definition of "de novo". Oxford Nanopore has shown interest in the space but no POC as of yet.
More on #Proteomics of the Next-Generation at

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Feb 10
A summary of announcements/highlights from #AGBT23 (in no particular order):
#AGBT23 cfDNA methylation profiling as a blood biomarker for Congestive Heart Failure. This is from the same team that gave you the @GrailBio Methylation Atlas, now applied to biomarker discovery.…
#AGBT23 Miga on the comparison between PacBio Revio and Oxford @nanopore High Duplex / UltraLong reads. PacBio 21/46 T2T and ONT 24/46 (higher is better). Ultralong reads scaffolding for both (unconfirmed) would mean ONT lead is even bigger.
Read 13 tweets
Feb 9
#AGBT23 More details on the $ILMN Illumina Infinity reads technology from Alex Aravanis (post from LinkedIn).
Also first data shared on XLEAP-SBS chemistry for the NextSeq 1000/2000 instruments. Not sure why would anyone buy one of these instruments given the alternatives from @ElemBio and @CompleteGenomic 's G400.
First shipment on NovaSeq X: if Illumina can beat the competition at anything in the next few months, it'll be on manufacturing and deployment of the NovaSeq X.
Read 4 tweets
Feb 8
Given all the talk of $100 genomes and tens of thousands of genomes being sequenced per year on a single instrument, the question arises: how many of these sequencing factories are we going to see? how many genome equivalents do we need capacity for?
Taking the 50,000 genomes a year mark as a starting number, and considering we have 140 million new-borns a year, we would need 2,800 DNBSEQ T20 factories distributed around the world only to keep up with the new-born human population.
If we consider that about 10% of the world population is older than 65 years, that's 788 million people. If we rounded up to 1 billion people needing cancer screening via liquid biopsy, and estimated the sequencing needed to be 1/10th of a human genome equivalent, then
Read 8 tweets
Feb 8
In #NextGenerationSequencing, @CompleteGenomic's new of the <$100/genome with their DNBSEQ T20 available from Q3 2023, and their T7x3 $130/genome pricing, we now have 3 companies that have hit the $200/genome mark with announcements: @ElemBio $ILMN Illumina and Complete Genomics.
Both $ILMN Illumina and @CompleteGenomic's will hit the $200/genome and <$100/genome mark in the second half of 2023, but @ElemBio Element Bio AVITIx3 and Complete Genomics T7x3 pricing models are *now* available at $200/genome and $130/genome respectively.
Also @UltimaGenomics is working on their U100 instrument aiming at $100/genome, and had several announcements of partnerships with library prep providers at #AGBT23.
Read 4 tweets
Jan 13
In #JPM2023, $NAUT Nautilus Bio didn't make their slides available, but they have a slide deck from an investor meeting in December 2022. They intend to launch their Proteome Analysis Platform in Mid-2024.
They see a market opportunity of $25B, where 50% would be BioPharma customers, and 20% Academic and Research.
One of the biggest piece of news is that $NAUT Nautilus Bio recently partnered with Abcam to enhance their affinity reagent development program.
Read 7 tweets
Jan 13
In #JPM2023 news, $SEER also presented. They are another of the Next Generation Proteomics Sequencing players. One of their USPs is that they have an approach capable of finding different protein variants that would be undistinguishable with affinity-based approaches.
This includes slice variants, where the "Peptide Level" identification allows them to detect meaningful differences where other approaches are not able to.
Since their method is based on peptides, they can go into the 1M+ elements per run, where panel-based affinity methods are limited to the thousands or maybe tens of thousands.
Read 4 tweets

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