Thread by @investing_city

Genomics Thread #4

Today we're talking about synthetic long-read companies like 10x Genomics and Bionano Genomics...

1/ In the last thread, we discussed the differences between SRS and LRS (go back and read if you need a refresher).

SRS is owned by Illumina and they have brought costs down a crazy amount.

LRS is being pioneered by PacBio and Oxford Nanopore.

2/ But in the past 5 years, there has been a lot of innovation in synthetic long-read sequencing.

The leader here is 10x Genomics.

Broadly speaking, using 10x's Chromium system, researchers can get comparable read lengths at a lower cost than true LRS.

3/ The way it works is through bar-coding each cell or DNA fragment.

The technology is called next-gen GEM (Gel beads in EMulsion).

Essentially, this bar-coding enables a more thorough assembly of short-read sequencing runs.

4/ So instead of purchasing an entire SMRT system made by PacBio, you can utilize your existing Illumina machines in tandem with 10x's Chromium/library prep kits.

In short, it helps you save money.

Here are all of 10x's products:

5/ Recently, 10x has acquired 3 different companies in the spatial genomics space.

The idea is to sequence RNA in its native tissue environment (aka in situ).

Their product in this space is called Visium and it can be used with any imaging microscope.

6/ In 2018, 10x settled with Bio-Rad in a patent infringement case that ultimately led to 10x winding down its "linked-reads" product.

What it does today is very similar but it's mainly focused on RNA and the GEM tech is more advanced.

The other competitor here is NanoString.

7/ Another LRS company to watch is Bionano Genomics.

Bionano's system is called Saphyr and it is the dominant platform in optical mapping.

8/ Optical mapping is also complementary to SRS.

The goal is to find structural protein variations.

As you might remember, one of the big shortcomings of SRS is that it's good for detecting single nucleotide variations but the DNA length is too short for more nuanced mutations.

9/ Bionano and 10x aren't really considered competitors even though their core goals are similar: complementing SRS to get a more full picture of the transcriptome (RNA).

I think eventually they may encroach more on each other's space but they can also be used in tandem.

10/ Both $BNGO and $TXG have appreciated a lot in the past year so there is clearly some buzz around their products.

I don't quite know what to make of these products versus pure-play LRS companies.

I think there are definitely trade-offs.

End/ One concern about synthetic LRS is that the pure LRS companies will continue to bring down costs and add richer optical mapping on top of their tech.

On the other hand, synthetic LRS allows researchers to be platform agnostic.

I'd love to hear feedback from experts!