In PLOS Genetics, researchers from Switzerland and the UK outline genomic and transcriptomic features found in a rare form of eye cancer called conjunctival melanoma, which arises from melanocyte cells. Using exome sequencing or whole-genome sequencing, the team assessed more than a dozen pairs of tumor and matched normal samples, uncovering high mutational loads, a mutation signature with potential ties to ultraviolet light exposure, and recurrent mutations in ACSS3, BRAF, NF1, and other genes. Those somatic alterations were bolstered by RNA sequence data on a subset of the tumor samples, and through comparisons with sequence data from cutaneous melanoma. "Our results showed that conjunctival melanoma is genetically very similar to cutaneous melanoma," the authors report, calling ACSS3 a previously unappreciated "potential key player in oncogenesis of conjunctival melanoma."
A team from Canada, Japan, and the US presents findings from a phylogenetic analysis of more than 8,800 Clostridioides difficile genomes for a paper published in PLOS Pathogens. The researchers brought together genome sequences for 8,839 strains of the bug, which can cause gastrointestinal infections in individuals with altered gut microbial communities after antibiotic treatment. In the process, they tracked down a dozen subtypes based on sequences for the tcdB toxin gene and seven subtypes based on almost 5,200 tcdA toxin gene sequences, highlighting the possibility of using toxin-based subtyping in the clinical setting — a strategy that was subsequently tested using 351 C. difficile isolates collected at Brigham and Women's Hospital.
For a paper appearing in PLOS One, investigators in Thailand take a look at multidrug- and extensively drug-resistant Mycobacterium tuberculosis isolates using a combination of whole-genome sequencing, genotypic drug susceptibility profiling, and minimum inhibitory drug concentration data. With the help of genotypic drug susceptibility insights spanning 60 M. tuberculosis isolates originating in Thailand, the team tracked down mutations that appeared to coincide with distinct tuberculosis (TB) drug resistance profiles. The authors argue that these and other findings "emphasize the high applicability of [whole-genome sequencing] for TB diagnosis including determination of drug resistance, mutated allele association with [minimum inhibitory concentration (MIC)], and heteroresistance associated with MIC."