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UK Team Presents Genetic, Epigenetic Sequencing Method

A University of Cambridge and Cambridge Epigenetix team outlines a sequencing strategy for profiling 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) epigenetic marks in concert with whole-genome sequencing. As they report in Nature Biotechnology, the researchers relied on an enzymatic DNA processing approach for their six-letter sequencing method, which is designed to pick up 5mC and 5hmC as well as all four canonical DNA bases on existing DNA sequencing platforms. After testing a five-letter version of the approach, used to sequence four DNA bases and modified cytosines (5mC and 5hmC) across the genome in a B lymphoblast human cell line on the Illumina Novaseq platform, they tweaked the approach to distinguish between 5mC and 5hmC using DNA methyltransferase 5 and beta-glycosyltransferase enzymes to assess 5mC and protect 5hmC through glycosylation, respectively. The authors found that the six-letter sequencing strategy unearthed 5mC marks with more than 95 percent accuracy in aligned reads, while finding nearly 98 percent of 5hmC bases and offering some 99.9 percent accuracy when it came to sequences for unmodified cytosine bases. "As the platform fundamentally uses Watson-Crick base pairing to decode information," they write, "it can be made readily compatible with any sequencer platform and we see opportunities for its future application to long-read sequencing and single-cell analysis."

The Scan

Harvard Team Report One-Time Base Editing Treatment for Motor Neuron Disease in Mice

A base-editing approach restored SMN levels and improved motor function in a mouse model of spinal muscular atrophy, a new Science paper reports.

International Team Examines History of North American Horses

Genetic and other analyses presented in Science find that horses spread to the northern Rockies and Great Plains by the first half of the 17th century.

New Study Examines Genetic Dominance Within UK Biobank

Researchers analyze instances of genetic dominance within UK Biobank data, as they report in Science.

Cell Signaling Pathway Identified as Metastasis Suppressor

A new study in Nature homes in on the STING pathway as a suppressor of metastasis in a mouse model of lung cancer.