A team from the UK and Kenya describe a sequencing-based strategy for characterizing cell surface proteins that the Trypanosoma congolense trypanosome parasite uses to evade the human immune system. The researchers focused on a form of antigenic variation involving variant surface glycoprotein (VSG) switching, using their deep sequence- and motif-based Variant Antigen Profile method to assess genome sequence data from 41 T. congolense representatives from half a dozen African countries. In addition to verifying the universality of 15 previously identified VSG phylotypes, for example, they considered VAPs in the context of trypanosome geography and population structure. The authors applied a similar approach to transcriptomic data from pooled tsetse fly mouthparts to investigate T. congolense VSG phylotypes expressed in parasites carried by two dozen flies.
Using a Transposable Element Analyzer method, combined with genome and transcriptome sequences from 189 stomach, colorectal, and esophageal tumors, researchers in Korea and the US explore the molecular and clinical features associated with enhanced or muted long intersperse nuclear element-1 (L1) retrotransposon activity in cancer. While L1 activity is typically suppressed in cancer-free somatic tissues, the team explains, these retrotransposons can contribute to genome instability and rearrangements through insertional mutagenesis when they do become active. Among other patterns, the authors found that L1 insertions increased with advanced patient age, higher tumor grade, or tumor TP53 mutation, for example, but declined in tumor with pronounced immune activity. "Our results indicate that cancer immunity may contribute to genome stability by suppressing L1 retrotransposition in gastrointestinal cancers," they write.
Finally, a Cold Spring Harbor Laboratory- and Johns Hopkins University-led team presents a detailed map of structural variation in a HER2-expressing breast cancer cell line called SK-BR-3, based on Pacific Biosciences long-read sequences. After generating nearly 72-fold average coverage for the SK-BR-3 line, the researchers searched for structural variants using an alignment-based method dubbed Sniffles — an analysis that led to more than 8,900 insertions, nearly 6,950 deletions, 1,018 duplications, and 279 inversions involving 50 or more base pairs of sequence. Among them were complex duplications and translocations clustered around the HER2/ERBB2 oncogene, the authors report, noting that the long read sequencing approach led to "a great variety of mutations including complex variants and gene fusions far beyond what is possible with alternative approaches."