In PLOS Genetics, researchers at the University of Cambridge and other centers in the UK describe a "noise-augmented von Mises-Fisher model" (NAvMix) designed to focus in on biological pathways involved in traits or conditions assessed using genome-wide association studies — an approach the team applied to simulated data and to body mass index (BMI)-associated variants, uncovering a variant cluster linked to increased BMI and lower-than-usual heart disease risk. "We present a new procedure for clustering variants based on their proportional associations with different traits, which is more reflective of the underlying mechanisms to which they relate," the authors write, explaining that "[w]e apply the method to genetic variants associated with BMI and then study the effects of each of the identified groups of variants on coronary heart disease."
A team from Pakistan presents findings from microbiome analyses of dozens of urinary tract infection (UTI)-related urine samples in PLOS One, focusing on antimicrobial susceptibility and resistance patterns as well as phylogenetic relationships between uropathogens such as Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus found in the samples. The researchers identified E. coli in more than half of the 50 UTI patient urine samples tested, for example, including an over-representation of E. coli isolates containing ampicillin resistance genes. They note that more than one-quarter of the samples contained K. pneumoniae and 14 percent were marked by S. aureus strains. The phylogenetic analyses suggest uropathogen sequences "are closely linked," the authors conclude, with antibiotic susceptibility testing pointing to extensive resistance to commercial antibiotics in E. coli and S. aureus strains.
Investigators in Brazil uncover rare variants associated with cutaneous melanoma susceptibility for another paper in PLOS One. With exome sequencing on 10 individuals from five pathogenic CDKN2A and CDK4 mutation-free melanoma-affected families in Brazil, the team tracked down nearly 300 rare protein-coding variants found in multiple melanoma-affected members from each family. With a series of gene function, pathway, and variant analyses, the authors subsequently narrowed in on several new candidate genes for cutaneous melanoma susceptibility, along with genes identified in the past. "Our data revealed rare germline alterations segregating in patients with familial melanoma, providing new knowledge regarding melanoma predisposition in the Brazilian population," they write, noting that "we underscored the putative role of particular genes for melanoma risk, contributing with a novel set of potential candidate genes that can be explored further in future studies."