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Genome Biology Papers on Long Tail Cancer Mutations, Circular RNA Pipeline, Stem Cell Differentiation

A Yale University-led team looks at the "long tail" of genes marked by recurrent mutations across 17 cancer types. With the help of a new network propagation analytical strategy, the researchers analyzed protein-protein interaction networks for genes expressed in Cancer Genome Atlas project profiles, searching for so-called "upward mobility genes" with rare-to-moderate mutation frequencies that alter interactions for the genes or related pathways in ways that "significantly propel their mutation frequency-based rank upwards during [cancer] propagation." Their search highlighted 18 genes that were not linked to cancer in the past, which were validated using new and available RNA interference, CRISPR gene editing, and gene knockdown experiments.

Researchers from Israel and ­the US present a pipeline for prioritizing circular RNAs (SRCP). The two-step "short read circRNA pipeline" (SRCP) is designed for comprehensively detecting and tallying circRNAs based on RNA sequence data, the team says, noting that SRCP is also capable of quantifying circRNAs tracked down with alternative pipelines. After cataloging circRNAs in newly RNA-sequenced mouse, rat, monkey, or human tissue samples, for example, the authors applied SRCP to their search for AGO2 microRNA effector protein-interacting circRNAs in the human brain. There, they note, "only a handful of circRNAs are strongly bound to AGO2 and could potentially regulate the function of specific miRNAs."

A University of Washington-led team tracks nuclear structure, chromatin accessibility, and gene expression profiles in differentiating mouse embryonic stem cells. Using a combination of single-cell RNA sequencing, Hi-C-based chromosome interactions, and chromatin accessibility clues gleaned from ATAC-seq data, the researchers assessed allele-specific features in mouse embryonic stem cells during and after the differentiation process, detecting differences between differentiated stem cells with or without inactivated X chromosomes. "Based on [allelic] trajectory analyses, three distinct nuclear structure states are detected reflecting discrete and profound simultaneous changes not only to the structure of the X chromosomes, but also to that of autosomes during differentiation," the authors report, noting that "long-range structural changes to chromosomes appear as discrete events, unlike progressive changes in gene expression and chromatin accessibility."