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PNAS Papers on Diffuse Large B Cell Lymphoma, Sterile Male Mosquitoes, Infectious Disease Signatures

An international team led by investigators at Columbia University looks at immune escape and lower-than-usual levels of class I major histocompatibility complex (MHC-I) expression in a subset of diffuse large B cell lymphoma (DLBCL) cases. Based on exome sequencing and targeted deep sequencing focused on human leukocyte antigen (HLA) regions of the genome in dozens of DLBCL samples, the researchers identified recurrent somatic alterations in cases with or without MHC-1 expression, including a subset of tumors with monoallelic HLA-1 deletions that appeared to impede neoantigen presentation to immune cells despite high tumor mutational loads. Together with data from other cancer types and from follow-up experiments in mouse germinal-center B cells, the results suggest that "homozygosis of HLA-I loci is significantly and preferentially enriched in the germline of DLBCL patients," the authors write, "suggesting a stepwise process by which limited neoantigen presentation is selected during DLBCL development."

University of California researchers report on results from a CRISPR-Cas9-based genome editing approach used to introduce a male fertility-altering beta-2-tubulin (B2t) mutation in Aedes aegypti mosquitoes. Although the resulting male mosquitoes lacked sperm production and successfully suppressed female fertility, the team found that the genome editing approach did not alter other fitness features in the affected Ae. aegypti individuals, suggesting it may be suitable for "sterile insect technique" (SIT) applications. "While SIT has been successful in suppressing certain agricultural pests, it has been less effective in depressing populations of Ae. Aegypti," the authors explain, noting that the latest results "raise the possibility of employing B2t sterile males to improve the efficacy of SIT in suppressing populations of Ae. Aegypti through repeated releases and thereby reduce the transmission of viruses by these invasive mosquitoes."

A team from Vir Biotechnology, Washington University School of Medicine, and the University of Texas Southwestern Medical Center describes so-called "transfer signatures," or gene expression profiles that appear to be shared between related infectious diseases in humans and model host animals. Using machine-learning methods, available gene expression data, and RNA sequencing profiles representing blood samples collected from infected human or macaque individuals, the investigators showed that the transfer signature strategy predict gene expression patterns related to immunophenotypes for everything from latent tuberculosis progression to active disease to COVID-19 severity or influenza A H1N1 infection. "Our work establishes the validity of this approach and explores the nature of human immunophenotypes," the authors write. "If generally applicable in additional studies, the methods described here may lead to a rapid evolution of clinically and biologically relevant concepts in immunity and pathogenesis."

The Scan

Billions for Antivirals

The US is putting $3.2 billion toward a program to develop antivirals to treat COVID-19 in its early stages, the Wall Street Journal reports.

NFT of the Web

Tim Berners-Lee, who developed the World Wide Web, is auctioning its original source code as a non-fungible token, Reuters reports.

23andMe on the Nasdaq

23andMe's shares rose more than 20 percent following its merger with a special purpose acquisition company, as GenomeWeb has reported.

Science Papers Present GWAS of Brain Structure, System for Controlled Gene Transfer

In Science this week: genome-wide association study ties variants to white matter stricture in the brain, and more.