DoveTail Transposes Their Hi-C Methodology

Technologies vying for state-of-the-art in human genome analysis are a recurrent theme in this space, and there are many ideas on this in the collection I really need to get out over the next two weeks before my brain is overwhelmed by London Calling.  Up today: Dovetail Genomics popping back on the scene (as a subsidiary of Cantata Bio)  with an AACR poster several weeks ago showing early results from a "LinkPrep" kit that will commercialize tagmentation (in vitro transposition to fragment DNA and add adapters) for Hi-C library generation, with the promise of enabling short read sequencing to deliver both SNVs as well as long-range structural information all from the same library.  

On The Expanding Versatility of Single Molecule Sequencing for Detecting Anomalous DNA

An exciting aspect of true single molecule sequencing has been the detection of methylated bases.  Both Oxford Nanopore and Pacific Biosciences technology generate altered signals if methylated bases are present.  For Oxford Nanopore this is hardly surprising, as it would seem any change in the DNA should alter the complex interaction with the protein pore and it should become just a computational challenge of recognizing that signal.  PacBio is a bit more surprising, but the kinetics of base incorporation are apparently sensitive to the complementary base.  I wanted to point out, though without much deep analysis, three recent preprints that demonstrate detection of other modifications to DNA and thereby enable some interesting applications (and of course, some wild speculations on my part).  It's also interesting because of the overlap between the papers, as they are interconnected to a degree in their methods.

First Illumina Complete Long Reads Preprint

Readers of this space might have detected a significant slant towards skepticism in my coverage of Illumina Complete Long Reads (iCLR), exacerbated by now deposed Illumina CEO Francis deSouza claiming it isn't a synthetic read technology.  Illumina's posters on iCLR at AGBT this year seemed to reinforce my view that Illumina was marketing purely on short-read like terms - call SNPs in a few more hard-to-map regions of the genome, but not really compete head-to-head with the true long read platforms.  But now there is a preprint out on MedRxiv that reports iCLR results for a Genome In A Bottle (GIAB) sample as well as seven samples from individuals wiith potential genetic diseases of unresolved cause.  The GIAB sample was also sequenced with some of the latest Oxford Nanopore chemistry (Duplex R10.4.1) and as HiFi libraries on PacBio Revio - enabling comparisons of the platforms.  The preprint is probably going to be revised and expanded - I'm certainly hoping some of my comments are found constructive - but is very useful to see.  And perhaps it will soften positions such as mine on iCLR's utility.