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PLOS Papers on Neuropsychiatric Drug Targets, Genome Sequence for Potential Foodborne Pathogen, More

In PLOS Genetics, members of the Accelerating Medicines Partnership for Alzheimer's Disease (AMP-AD) consortium outline findings from a brain transcriptome-based search for neurological and psychiatric disease drug targets. Starting from brain-based expression quantitative trait loci found in nearly 1,300 RNA sequenced samples from the AMP-AD and the CommonMind consortium efforts, the team used Mendelian Randomization and Bayesian colocalization analyses to come up with causal variants and candidate drug targets for a dozen neurological and psychiatric disease, narrowing in on expression changes with ties to conditions ranging from Alzheimer's or Parkinson's diseases to schizophrenia or bipolar disorder. "We found a causal relationship between the change in expression of 47 genes and increased disease risk across the 12 diseases we tested," the authors report. "As drug targets with human genetic evidence are far more likely to be approved in clinical trials, these findings provide a valuable list of potential therapeutic targets, including the ACE, GPNMB, KCNQ5, RER, and SUOX genes."

A team from Korea and Belgium takes a look at virulence factors and antibiotic resistance genes in a foodborne KM1 isolate of the bacterial species Pantoea agglomerans, first isolated from short-fermented homemade kimchi, for a paper in PLOS One. By sequencing and analyzing the more than 4 million base pairs in the circular genome of P. agglomerans KM1, along with a handful of accompanying mega plasmids and prophages, the investigators tracked down several virulence factors, gene adaptations related to stress and hosts responses, and more than a dozen known antibiotic resistance genes in the proposed opportunistic pathogen. Along with follow-up immunostimulatory experiments in a mouse macrophage cell line, the authors suggest that the whole-genome sequence data "provided in-depth characterization of P. agglomerans KM1 isolate, shedding a new light on determinants of virulence that drive its interactions with the environment, other microorganisms, and eukaryotic hosts."

Researchers in the US and China demonstrate the feasibility of sequencing larvae from the blood fluke Schistosoma japonicum from archived infection samples for a paper appearing in PLOS Neglected Tropical Diseases. Using whole-genome amplification and whole-genome sequencing (WGS), the team assessed 22 S. japonicum larvae from 11 infected individuals from two Chinese villages, focusing on the so-called miracidia stage of the schistosome larvae. The resulting sequence data made it possible to identify genetic diversity and schistosome relatedness patterns in the human isolates, they report, suggesting that "population-level WGS datasets are attainable for individual miracidia and represent a powerful tool for ultimately providing insight into overall genetic diversity, parasite relatedness, and transmission patterns for better design and evaluation of disease control efforts."