In PLoS Medicine this week, researchers from the Breast Cancer Association Consortium and their collaborators report their classification of breast cancer subtypes for disease outcome over time based on five immunohistochemical markers. In examining 10,159 cases from 12 individual cohorts, the team found that the different patterns of mortality over time that they observed "suggest[s] important biological differences between the subtypes that may result in differences in response to specific therapies, and that stratification of breast cancers by clinically relevant subtypes in clinical trials is urgently required."
Curtis Huttenhower and Oliver Hofmann at the Harvard School of Public health provide "a quick guide to large-scale genomic data mining" in PLoS Computational Biology this week. In it, the authors write that "many convenient computational tools for individual dataset analysis will scale poorly to repositories of hundreds or thousands of genome-scale experimental results," and "since data are becoming available at a rate that outpaces even Moore's law, it is not enough to wait for faster computers to execute longer and longer queries, and new bioinformatic tools must be developed with an eye to scalability and efficiency."
Also in PLoS Computational Biology, investigators at Yale University and their collaborators address the question, "how does the number of regulators scale with the number of targets?" using co-regulation networks to describe relationships between regulators and their target genes across five diverse species — from E. coli to human. They've also devised a "simple analytical model to show how new partnerships are acquired with an increasing number of target genes," the authors write.
And in PLoS Genetics this week, a trio of researchers in California present their method, which uses "orthologous sequences to predict the impact of amino acid substitutions on protein function." Using a yeast cell-based functional assay, the team examined a panel of nonsynonymous mutants of the human methylenetetrahydrofolate reductase enzyme — or MTHFR. "As expected, substitutions in human MTHFR at sites that are well-conserved across distant orthologs result in an impaired enzyme, while substitutions present in recently diverged sequences ... result in a functional enzyme," the authors write.