A University of California, Los Angeles-led team describes a hierarchical fine-mapping approach that brings together data at the genome, epigenome, and gene expression level. As they report in PLOS Genetics, the researchers' "pathfinder" fine-mapping framework is designed to account for both causal variants and chromatin marks that influence gene expression at sites of interest in the genome. "Our framework assumes a causal model where a SNP impacts a chromatin [mark] which in turn alters gene expression," they say. After demonstrating that pathfinder compared favorably to other fine-mapping methods for identifying causal SNPs in simulated data, the authors applied it to expression, chromatin, and genotyping data for 65 individuals of African ancestry and 47 individuals of European ancestry.
In PLOS Pathogens, National Institute of Allergy and Infectious Diseases researchers explore genetic factors affecting the lipopolysaccharide (LPS) composition of Coxiella burnetii, a gram-negative bacteria behind a zoonotic infection called Q fever that's carried by sheep, goats, and some cattle. The team noted that the virulent, full-length (a.k.a. "smooth") version of the C. burnetii LPS — found in phase I bacteria — is recognized by available Q fever vaccines, while phase II C. burnetii bacteria with "rough" LPS are non-virulent. The investigators uncovered high mutation levels in LPS biosynthesis genes through whole-genome sequencing on seven rough or intermediate LPS C. burnetii strains grown over several months, and subsequently used targeted mutagenesis and other approaches to identify half a dozen genes crucial for forming the smooth, phase I LPS.
Finally, in a PLOS One paper, a team from Denmark, Italy, France, and elsewhere outlines genomic and sub-genomic variations in a strain of the porcine epidemic diarrhea virus (PEDV) that has been passaged in pigs and cell cultures for decades. The researchers compared genome sequences generated at six labs with different sequencing protocols and starting stocks, focusing on the PEDV strain CV777. Although the sequences differed somewhat from one another and from a reference sequence for the coronavirus, they noted that the genomes were still more than 99 percent identical. The most pronounced variation in genome sequence and expression tended to cluster in certain parts of the genome, the authors explain, noting that it is "clearly important to know the features of the specific sample of CV777 being used for experimental studies."