Thread by @sbarnettARK

@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 @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 @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 ...

@nhawk45 @AlbertVilella ... and one can appreciate how a sequencer could struggle to differentiate so many unique states at a high speed, especially since mistakes are made all the time with DNA sequencing (only 4 states by comparison).

I'll switch gears to your question about 'single-molecule'.

@nhawk45 @AlbertVilella Illumina short-read DNA sequencing is a clonal, meaning that the instruments build a consensus from millions of amplified clusters of molecules. We can use all of nature's DNA machinery (polymerases, nucleases, etc) to amplify and detect molecules.

@nhawk45 @AlbertVilella We don't have this same luxury with proteins, meaning that an accurate consensus sequence needs to be generated from single molecules (bc we can't amplify proteins like we can w/ DNA).

PacBio/Nanopore platforms also exhibit single-molecule capabilities.

@nhawk45 @AlbertVilella Here's a broad overview of what QSI's protein sequencing workflow looks like.

As far as I know, QSI is gunning for full sequence and PTM detection, which is a high aspiration in the burgeoning proteomics space. Did I leave anything out?