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Nucleic Acids Research Papers on VirusViz, Methylation Sub-Population Analysis, BRCA2 Survival Screen

Investigators in Italy outline a method for visualizing, comparing, and analyzing variants in SARS-CoV-2 and other viral species at the nucleotide and amino acid level. The platform, known as VirusViz, includes a bioinformatics pipeline for analyzing viral data from the ViruSurf database or other sources, the team says, and provides variant visualization, metadata, and more on the viral populations and sub-populations considered. "The VirusViz system is a new powerful tool for supporting comparative virtual analysis of variants, both of nucleotides and of amino acids, accepting input from both public sequences and user-provided sequences, integrated with a curated knowledge base of variants of interest," the authors write, calling it "the only tool currently supporting user-defined grouping of sequences for the comparative inspection of variant distributions across groups."

A Washington University School of Medicine-led team describes a computational approach for looking at methylation patterns within cellular sub-populations or cancer clones. The researchers note that their "deconvolution of sub-populations existing in methylation data," or DXM, method is designed for detecting allelic sub-populations with distinct methylation marks based on bisulfite sequencing data. After comparing the tool with other methylation analysis methods, they applied DXM to data from dozens of diffuse large B-cell lymphoma samples, uncovering relapse-related allelic sub-populations with distinct methylation features. "We expect that DXM will have high applicability and utility for the analysis of sub-population methylation in any heterogeneous sample and in the future similar approach could be adapted to the analysis of cell-free DNA," the authors write.

Finally, investigators at the University of Texas MD Anderson Cancer Center and University of Texas Health Science Center at Houston present a role for cyclin C (CCNC) and other components of the RNA Polymerase II transcription mediator complex in survival in cells with lower-than-usual levels of BRCA2, providing clues to potential mechanisms of PARP inhibitor (PARPi) resistance. Using a whole-genome CRISPR screening strategy, the team searched for pathways that are required in the absence of BRCA2, uncovering reliance on CCNC in cells with inducible BRCA2 depletion — results that were subsequently assessed using RNA sequencing and other experiments. "Taken together, our data reveal CCNC as a critical genetic determinant upon BRCA2 loss of function, which may help the development of novel therapeutic strategies that overcome PARPi resistance," the authors write.

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