In the early, online edition of the Proceedings of the National Academy of Sciences, researchers from the Fred Hutchinson Cancer Research Center, the University of Washington, and elsewhere use pan-cancer profiling to explore biologic pathway changes that stem from mutations in the tumor suppressor gene Fbw7, which codes for a ubiquitin ligase enzyme that flags oncoproteins for degradation. Through a pan-cancer analysis that relied on data produced for the Cancer Genome Atlas project, the team untangled an expression signature shared across Fbw7-mutated tumors, including a rise in metabolic processes involving oxidative phosphorylation — changes that were subsequently verified in colorectal cancer cell lines with Fbw7 mutations. "Our approach revealed unexpected metabolic reprogramming and possible therapeutic targets in Fbw7-mutant cancer cells," the authors note, "and provides a framework to study other complex oncogenic mutations."
A Wageningen University-led team takes a look at the roots of nitrogen-fixing nodules using comparative genomics and analyses of nodulating non-legume plants such as Parasponia andersonii. The researchers compared genomic and transcriptomic sequences for P. andersonii and related, non-nodulating Trema plants to one another and to sequences from the legume Medicago truncatula, identifying hundreds of symbiosis- and nodulation-related genes in nodulating Parasponia and legume plants that appear to have been lost in related non-nodulating plants. Such findings "raise the possibility that nodulation originated only once and was subsequently lost in many descendant lineages," the authors say.
Researchers from Mexico and the US apply a new strategy for de novo detection of single nucleotide variants in the human genome. The approach — known as "coverage-based single nucleotide variant identification," or COBASI — "uses only perfect matches between the reads of a sequence project and a reference genome to detect and accurately identify de novo SNVs," they explain. When the team applied COBASI to whole-genome sequences from a parent-child trio, for example, it tracked down 58 de novo SNVs in the child's genome, including 52 variants that were verified experimentally by PCR. "The number of discovered variants could be an underestimate," the authors say, noting that "our main interest is in maximizing the precision in the called variants to diminish as much as possible the extent of experimental validation that is required."