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Nucleic Acids Research Papers on RIMS-seq, MMBIR in Cancer, Induced Pluripotent Cell Transposable Elements

Researchers in the US and France report on a "rapid identification of methylase specificity" sequencing (RIMS-seq) approach for characterizing 5-methylcytosine methylation-related methylase enzyme specificity in concert with DNA sequencing in bacterial genomes. After validating the sequencing strategy, the team used RIMS-seq to assess synthetic and real gut microbial communities or skin microbiomes, where the approach appeared to compare favorably with available DNA sequencing and bisulfite sequencing methods. "RIMS-seq shows comparable sequencing quality as DNA-seq and accurately identifies methylase specificities," the authors report. "Applied to characterized strains or novel isolates, RIMS-seq de novo identifies novel activities without the need for a reference genome and permits the assembly of the bacterial genome at metrics comparable to standard shotgun sequencing."

A team from the University of Iowa identifies insertions stemming from microhomology-mediated bread-induced replication (MMBIR) events in cancer. With the help of their MMBSearch software, the investigators saw an overrepresentation of so-called MMB-Tis templated insertions stemming from MMBIR in cancer cells, in dozens of tumor samples profiled for the Cancer Genome Atlas, and in lung adenocarcinoma samples sequenced for the study. "[W]e observed that MMB-Tis readily accumulate de novo across several cancer types, with particularly high accumulation in some breast and lung cancers," they report. "By contrast, MMB-TIs appear only as germline variants in normal human fibroblast cells, and do not accumulate as de novo somatic mutations."

Finally, researchers in China and the UK describe transposable element insertions in human pluripotent stem cells (hPSCs). Based on its long- and short-read RNA sequencing analyses of hPSCs, the team uncovered transposable element-related sequences in more than one-quarter of the predicted protein-coding sequences and in roughly 65 percent of non-coding transcript sequences assessed — insertions that varied to some extent depending on the transposable element family considered. "Overall," the authors report, "our comprehensive analysis demonstrates that the incorporation of TE sequences into the RNAs of hPSCs is more widespread and has a greater impact than previously appreciated."

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