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Nucleic Acids Research Papers on Malaria Hydroxymethylation, Single-Cell Sequence Clustering, More

Researchers from France, the US, and Singapore describe cytosine hydroxymethylation (5hmC) modifications that appear to coincide with gene expression in the malaria-causing parasite Plasmodium falciparum. Using enzyme-linked immunosorbent assays, RNA sequencing, hydroxymethylated DNA-immunoprecipitation sequencing, mass spec, and other approaches, the team saw 5hmC levels that appeared to outpace cytosine methylation levels in the parasite's asexual life stage. "The identification of a novel predominant type of cytosine modification points to a new epigenetic layer that contributes to [messenger RNA expression in P. falciparum]," they write, noting that the study "raises interest to exploit cytosine modifications for new intervention strategies against malaria parasites."

A University of North Carolina at Chapel Hill and University of California, San Francisco, team introduces a computational approach for clustering sequences from individual cells profiled by RNA sequencing. The mixture-model method — known as "single-cell, aggregated clustering via mixture model ensemble" (SAME)-clustering — appears to offer advantages over unsupervised clustering methods, the researchers say, while the broader clustering strategy is expected to be applicable to other types of data. When they applied SAME-clustering to more than a dozen single-cell RNA-seq datasets, for example, the authors found that the "SAME-clustering ensemble method yields enhanced clustering, in terms of both assignments and number of clusters."

Michigan State University researchers retrace RNA-editing patterns involving a handful of genes suspected of dual coding in cell lines from Trypanosoma brucei, a protozoan parasite that can be transmitted to mammals via tsetse fly bites. Prior studies have shown that T. brucei uses a guide RNA-based editing system to modify specific bases in messenger RNAs produced from mitochondrial sequences, the team says, noting that individual genes undergoing alternative RNA editing may be capable of coding for two distinct proteins. Based on open reading frame use detected in transcripts profiled by deep RNA sequencing in two T. brucei cell lines, the authors conclude that the "[guide RNA]-guided editing system can respond to different metabolic conditions and also dramatically increase protein diversity in spite of a rigid and mutationally fragile system."