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This Week in Science: Aug 27, 2010

In Science this week, researchers at the New York University School of Medicine and their colleagues compare the genome sequences of the ants Camponotus floridanus and Harpegnathos saltator. Both species' genomes, the authors write, "contained high amounts of CpG, despite the presence of DNA methylation." In their gene expression comparisons, Roberto Bonasio et al. found an "up-regulation of telomerase and sirtuin deacetylases in longer-lived H. saltator reproductives, caste-specific expression of microRNAs and SMYD histone methyltransferases, and differential regulation of genes implicated in neuronal function and chemical communication." The team suggests that their study presents a new model to investigate the epigenetics of aging and behavior. See our sister publication GenomeWeb Daily News' coverage of the study here.

In a paper published online in advance in Science this week, investigators at the Yale University School of Medicine, the University of California, San Francisco, and other institutions suggest that "mitotic recombination in patients with ichthyosis causes reversion of dominant mutations in KRT10." Keith Choate and colleagues show that ichthyosis with confetti, "a severe, sporadic skin disease in humans, is associated with thousands of revertant clones of normal skin that arise from loss of heterozygosity on chromosome 17q via mitotic recombination." The authors write that their analyses suggest that stem cell clones "are under strong positive selection" in affected individuals.

In Science Signaling this week, a public-private research team shows that Akt–RSK–S6 kinase signaling networks are activated by oncogenic receptor tyrosine kinases. Specifically, the authors write that with their large-scale proteomic approach they found "more than 300 substrates of this kinase family in cancer cell lines driven by the c-Met, epidermal growth factor receptor, or platelet-derived growth factor receptor-α RTKs." Additionally, they "identified a subset of proteins with RxRxxS/T sites for which phosphorylation was decreased by RTK inhibitors," and suggest that Akt–RSK–S6 kinase substrates "merit further consideration as targets for combination therapy with RTKIs."

And in a Perspectives piece in Science Translational Medicine this week, international investigators provide their "recommendations for biomarker identification and qualification in clinical proteomics." Harald Mischak at Mosaiques Diagnostics, based in Hannover, Germany, and 48 co-authors write that "the inability to verify some candidate molecules in subsequent studies has led to skepticism among many clinicians and regulatory bodies" and "assert that successful studies generally use suitable statistical approaches for biomarker definition and confirm results in independent test sets," which they describe in detail. Mischak et al. suggest that their "recommendations should help put proteomic biomarker discovery on the solid ground needed for turning the old promise into a new reality."

The Scan

Study Finds Sorghum Genetic Loci Influencing Composition, Function of Human Gut Microbes

Focusing on microbes found in the human gut microbiome, researchers in Nature Communications identified 10 sorghum loci that appear to influence the microbial taxa or microbial metabolite features.

Treatment Costs May Not Coincide With R&D Investment, Study Suggests

Researchers in JAMA Network Open did not find an association between ultimate treatment costs and investments in a drug when they analyzed available data on 60 approved drugs.

Sleep-Related Variants Show Low Penetrance in Large Population Analysis

A limited number of variants had documented sleep effects in an investigation in PLOS Genetics of 10 genes with reported sleep ties in nearly 192,000 participants in four population studies.

Researchers Develop Polygenic Risk Scores for Dozens of Disease-Related Exposures

With genetic data from two large population cohorts and summary statistics from prior genome-wide association studies, researchers came up with 27 exposure polygenic risk scores in the American Journal of Human Genetics.