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This Week in Nature: Apr 25, 2019

In Nature Methods this week, a team led by University of Oxford scientists describes a genomic single-molecule technique for measuring replication fork movement by detecting nucleotide analog signal currents on extremely long nanopore traces. The researchers use the method — dubbed D-NAscent — to study Saccharomyces cerevisiae chromosome biology, generating a whole-genome map of replication dynamics at a single-molecule level and uncovering a class of replication origins that they say could not have been found with established methods.

And in Nature Biotechnology, University of Washington investigators report a method for increasing the accuracy of nanopore DNA sequencing by varying cross-membrane voltage, which changes how a DNA strand moves through the nanopore. This approach, they write, reduces the impact of the two primary error types that affect sequencing accuracy: enzyme mis-steps and sequences with indistinguishable signals. Incorporating the variable-voltage method into nanopore sequencing platforms "will enable wide-scale improvement of all nanopore-based DNA sequencing applications, including species identification, epigenetic mapping, and higher accuracy de novo genome sequencing at lower coverage," the team concludes.

In Nature Medicine, a multi-institute group of scientists discusses the WINTHER trial, a clinical study examining the impact of tumor biopsy-derived DNA sequencing and RNA expression analysis on guiding cancer treatment decisions. Despite the trial's limitations — which include patient pretreatment and the small number of participating patients — it shows that "genomic and transcriptomic profiling are both useful for improving therapy recommendations and patient outcome, and expands personalized cancer treatment," the authors write. GenomeWeb has more on this, here.

Also in Nature Medicine, UK researchers present data from TARGET, a study evaluating the use of circulating tumor DNA sequencing to select patients for early-stage clinical trial enrollment. The investigators state that their findings support the routine implementation of ctDNA sequencing as an adjunct to tumor testing for patient stratification, and that advances in ctDNA assay technology may eventually make it possible to assign certain patients to blood-based testing alone. GenomeWeb also covers this study, here.