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PLOS Papers on Causal Variant Mapping, Ancient Salmonella, ALK Fusion Test for NSCLC

In PLOS Genetics, researchers from the University of California, Los Angeles, and the Harvard TH Chan School of Public Health describe a computational method known as "multiple study causal variants in associated regions," or MsCAVIAR, that expands on an existing "CAVIAR" approach to narrow in on causal variants with fine-mapping clues from multiple genome-wide association studies. After applying the open-source software to simulation data, the team used the method to find loci linked to high density lipoprotein levels based on data spanning multiple biobanks and participants from a range of ancestral backgrounds. "Our approach requires only summary statistics as opposed to genotype data and handles heterogeneity of effect sizes, differing samples sizes, and different [linkage disequilibrium] structures between studies, making trans-ethnic fine-mapping an ideal application," the authors write, adding that MsCAVIAR "is well-calibrated and improves fine-mapping resolution in simulation studies."

For a paper appearing in PLOS Pathogens, a team from China and Germany characterizes ancient Salmonella enterica microbes isolated from the remains of half a dozen individuals buried at a Bronze Age cemetery in what is now Xinjian, China. Based on whole-genome sequence data for the 3,000-year-old bugs — together with results from phylogenetic analyses that included four more ancient genomes and sequences from more than 200 modern strains from a lineage known as "Para C" — the investigators determined that the ancient S. enterica isolates from China fell into a group that was basal to the Para C lineage, and likely spread between humans along trade routes that existed at the time. "Altogether," they write, "our results show that Salmonella enterica infected humans in Eastern Eurasia at least 3,000 years ago, and provide the first ancient DNA evidence for the spread of a pathogen along the Proto-Silk Road."

Investigators in Taiwan outline a screening test designed to detect previously unappreciated rearrangements involving the ALK gene in non-small cell lung cancers (NSCLC). For a paper appearing in PLOS One, the team described its RT-PCR-based test for novel ALK fusions that may lend some NSCLC cases to treatment with ALK inhibitors. The approach, which can be applied to formalin-fixed, paraffin embedded (FFPE) tumor samples or to malignant pleural effusion (MPE) samples, compared favorably to existing immunohistochemistry methods for detecting ALK rearrangements, the authors note, reaching a sensitivity of 100 percent in both sample types, along with a specificity of almost 98 percent in the MPE samples and more than 97 percent specificity in the FFPE samples. "Due to potential false positivity, subsequent confirmation tests such as fluorescence in situ hybridization or multiple PCR would be preferable," they caution. "Nevertheless, the test is simple and inexpensive with no false negativity, making it a desirable screening test."