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Genome Biology Studies Explore Colorectal Cancer Progression, Secretion System in Cholera Bug, More

Researchers from the University of Chicago, Harvard Medical School, and elsewhere present findings from an analysis of colorectal cancer (CRC) progression, done using a bioinformatic tool to untangle somatic mutation timing in dozens of tumors. The team relied on whole-genome sequence data generated on 63 CRCs from the Cancer Genome Atlas project, establishing molecular clocks based on the allelic fractions found for various somatic single base changes, analyzed in the context of copy number and structural changes, aneuploidy events, rearrangements, and other tumor genome features. Among other recurrent patterns, the authors found that point mutations affecting driver genes such as APC tend to occur early in tumor development, as do some gene fusions and chromosome arm-level copy number losses. "Taken together," they write, "our results suggest sub-clonal copy changes can occur much earlier than the major clonal expansion."

A Georgia Institute of Technology-led team takes a look at a secretion system that the widespread marine microbe Vibrio cholerae uses to impale nearby cells and inject toxic effector proteins. With a combination of Pacific Biosciences long-read and Illumina short-read sequencing, the researchers did genome sequencing on 26 V. cholerae strains, using a newly developed bioinformatics tool to identify two previously unappreciated auxiliary gene clusters coding for the type VI secretion system (T6SS) of interest. They dug into one of these clusters — dubbed auxiliary cluster 5, or Aux5 — providing additional clues to its effector and immunity gene organization and activity. In addition, the authors suggest their bioinformatics tool "is better suited than previous methods for discovering novel T6SS effectors in V. cholerae species and may be adapted in the future to facilitate the discovery of effectors in other bacterial species."

Finally, investigators at the University of California-Davis, Yale School of Public Health, and other centers describe genome features found in tsetse flies from several Glossina species known for carrying trypanosome parasites that can cause trypanosomiasis in humans and other animals. The team compared genome sequences for six species from three sub-genera, using the sequence data to discern relationships between the flies and detect parts of the genome that have been streamlined or bolstered in relation to the Drosophila melanogaster fruit fly. "Expanded genomic discoveries reveal the genetics underlying Glossina biology and provide a rich body of knowledge for basic science and disease control," the researchers report, adding that the findings "provide insight into the evolutionary biology underlying novel adaptations and are relevant to applied aspects of vector control such as trap design and discovery of novel pest and disease control strategies."