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Genome Research Papers on Gut Microbe Antibiotic Response, Single-Cell RNA-Seq Clues to Metabolism, More

A Stanford University-led team tracks gut microbial community responses and dynamics after broad-spectrum oral antibiotic treatment for infectious disease. With the help of a linked-read metagenomic sequencing approach, the researchers performed deep sequencing on fecal samples collected over time from one individual going through antibiotic treatment and recovery, uncovering variants in three dozen gut species that were used to track microbiome dynamics —from antibiotics-related genetic shifts within microbial species to microbe variants that bounced back post-treatment. "[B]y tracking a host microbiome through periods of disease, antibiotic treatment, and recovery, we uncovered new evidence that the ecological resilience of microbial communities might extend all the way down to the genetic level," the researchers conclude. "Understanding how this resilience arises from the complex interplay between host genetic, epigenetic, and lifestyle factors, as well [as] its implications for broader evolution of the microbiome, remains and exciting avenue for future work."

A team from Indiana University School of Medicine, Purdue University, and Ohio State University presents a computational method for teasing metabolic features from single-cell RNA sequencing (scRNA-seq) profiles. The "single-cell flux estimation analysis" (scFEA) method is designed to map the metabolic "fluxome" in individual cells from scRNA-seq data, the researchers note. After validating the graph neural network-based method with synthetic data and with sample sets with available sequence and metabolic data, they applied scFEA to scRNA-seq and spatial transcriptome data from several publicly available datasets. "Overall, scFEA can efficiently delineate the sophisticated metabolic flux and imbalance specific to certain cell groups," the authors write. "We anticipate that it has the potential to decipher metabolic heterogeneity, and tease out the metabolic susceptibility to certain drugs, and ultimately warrant novel mechanistic and therapeutic insights of a diseased biological system at an unprecedented resolution."

Uppsala University researchers outline a strategy for doing chromatin accessibility analyses on archived formalin-fixed, paraffin-embedded (FFPE) tissue samples. "Accurate mapping of chromatin accessibility from FFPE specimens is challenging because of the high degree of DNA damage," they explain, noting that their "FFPE-ATAC" method can boost the quality of ATAC-seq libraries from FFPE nuclei using Tn5-mediated transposition adapters and T7 promoter sequence transcription in vitro. The team demonstrated that the FFPE-ATAC approach made it possible to produce high-quality maps of chromatin accessibility in nuclei from FFPE tissue samples, helping to uncover colorectal cancer (CRC)-related chromatin shifts in tumor tissues going back a decade or more from seven CRC patients.