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Open Bio Database Access Specifications, siRNA in the Clinic, and Making Sense of Missing Heritability

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Ten years ago, 20 biohackers gathered in a windowless room in Tucson, Ariz., to generate Open Bio Database Access specifications and provide bioinformatics developers with a suite of modules to access sequence data across multiple languages and platforms. At the time, the European Bioinformatics Institute's Ewan Birney told Genome Technology that the new specifications would benefit system administrators, database operators, and application developers alike. In November, Birney — who helped lead both the Ensembl and ENCODE projects and oversees EBI's nucleotide databases — and his colleague Rolf Apweiler were named future associate directors of the institute, and will succeed Graham Cameron upon his retirement in April.

For its March 2007 issue, GT spoke with Acuity Pharmaceuticals' Sam Reich, who was part of the R&D team that brought the first siRNA-based therapeutic to the US Food and Drug Administration for approval. "This is an important, novel class of compounds that will over time yield many drugs, and be a hugely important class of compounds for the biotechnology industry," Reich said of siRNAs. Since 2007, Acuity has operated as a subsidiary of Opko Health. In 2009, its VEGF-targeting siRNA drug bevasiranib became the first to enter a phase III clinical trial. The company terminated the trial later that year based on an independent data-monitoring committee recommendation.

Last year, GT dug deep into the world of undiscovered variants, finding much work left to be done to elucidate the sources of the so-called missing heritability. GT reported on an American Society for Human Genetics meeting talk given by the Broad Institute's Eric Lander, in which he said population studies have indicated that rare variants explain less heritability than common ones do. That the additive variation derived from GWAS had been less than expected is largely due to genetic interactions among loci, or epitasis, he added. In a January PNAS paper, Lander and his colleagues showed that "a substantial portion of missing heritability could arise from overestimation of the denominator, creating 'phantom heritability.'" Lander et al. sought to demonstrate that most current heritability estimates fail to account for genetic interactions among loci and that, as such, "the total heritability may be much smaller and thus the proportion of heritability explained much larger."

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