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Nature Papers Present Way to Boost Short-Read RNA-seq Transcriptome Accuracy, Sequencing Analysis of Breakthrough Infections

A method that improves the accuracy with which the set of expressed transcripts can be inferred from short RNA sequencing reads is presented in Nature Biotechnology this week. Assembling transcripts from short-read RNA sequencing data is limited by the lack of long-range information contained in each individual short read. At the same time, third-generation technologies are able to read full-length transcripts, but are limited by low throughput, a high error rate, and a high cost per base. To develop an alternative approach, a team led by scientists from Ludwig-Maximilians-Universität turned to an experimental-computational technique — called Ladder-seq — that separates transcripts according to their lengths before sequencing and uses the additional information to improve the quantification and assembly of transcripts. The method, the scientists write, "will allow research facilities to study the composition and dynamics of the transcriptome at an unprecedented level of accuracy based on a technology that has been established for over a decade."

Through an analysis of SARS-CoV-2 sequences from COVID-19 patients in the San Francisco Bay Area, a team led by scientists from the University of California, San Francisco, has found that vaccine breakthrough infections are mostly caused by immune-evading variants. As reported in Nature Microbiology this week, the investigators performed whole-genome sequencing and viral load measurements of nasal swabs, in conjunction with retrospective medical chart review, of 1,373 Bay Area COVID-19 patients between February and June 2021. They discover that vaccine breakthrough infections are overrepresented by immunity-evading variants as compared with unvaccinated infections, probably due to selection pressure in a highly vaccinated community. Notably, the researchers also found that symptomatic breakthrough infection and unvaccinated infections had comparable viral loads, suggesting that symptomatic breakthrough infections may be as efficient in spreading COVID-19 as unvaccinated infections, regardless of the infecting lineage.