The Critical Assessment of Genome Interpretation (CAGI) is a community experiment to assess computational methods for predicting the phenotypic impacts of genomic variation. The current CAGI experiment has eight open challenges, available on the CAGI website: https://genomeinterpretation.org/ In the CAGI experiment, participants are provided genetic variants and make predictions of resulting phenotypes. Independent assessors then evaluate these predictions against experimental characterizations. The primary goals of the experiment are to establish the current state of the art, identify bottlenecks in genome interpretation, inform critical areas of future research, and connect researchers from diverse disciplines whose expertise is essential for advancing methods for interpreting genomic variation. The deadline for current CAGI predictions is 28 March 2013. Anonymous submissions, with limitations, are allowed this year. https://genomeinterpretation.org/content/anonymity-policy We encourage use of both established methods and experimental approaches, and we welcome predictors of all backgrounds. The current CAGI experiment will culminate in a conference in Berlin, on 17-18 July 2013, immediately before the ISMB SIGs. An NHGRI R13 grant will help support travel and participation in the meeting. https://genomeinterpretation.org/content/cagi-2012-conference Previous CAGI experiments have highlighted striking breakthroughs as well as disappointing failures. Publications from the previous CAGI are underway; slides and posters presentations about CAGI may be found at: https://genomeinterpretation.org/content/cagi-presentations The results from the current CAGI challenge will be published as well. The currently open CAGI challenges are: + Seventy-seven PGP genomes (provided by George Church). Challenge: Predict clinical phenotypes from genome data, and match individuals to their health records. https://genomeinterpretation.org/content/PGP2012 + Exomes of Crohn's disease patients and healthy individuals (provided by Andre Franke). Challenge: predict which individuals have Crohn's. https://genomeinterpretation.org/content/new-crohns-dataset + Exomes from two families with lipid metabolism disorders (provided by John Kane and Pui-Yan Kwok). Challenge: predict lipid profiles and a causative variant. https://genomeinterpretation.org/content/FCH https://genomeinterpretation.org/content/HA + Variants in DNA double-strand break repair genes (provided by Sean Tavtigan). Challenge: predict probability of each variant occurring in a breast cancer case versus healthy control. https://genomeinterpretation.org/content/MRN + Mutations in p53 gene exons affecting mRNA splicing (provided by Jeremy Sanford). Challenge: predict how variants impact splicing. https://genomeinterpretation.org/content/Splicing-2012 + Variants of a p16 tumor suppressor protein (provided by Silvio Tosatto). Challenge: predict how well variants inhibit cell proliferation. https://genomeinterpretation.org/content/p16_2012 + Shewanella oneidensis MR-1 gene disruptions (provided by Adam Arkin). Challenge: Predict impact of microbial gene disruptions on cell growth under stress conditions https://genomeinterpretation.org/content/MR-1_2012 + riskSNPs disease-associated loci (provided by John Moult). Challenge: identify potential causative SNPs. https://genomeinterpretation.org/content/risksnps2012 We are also soliciting challenges for the next CAGI. Please contact us at cagi@genomeinterpretation.org with proposals for suitable datasets. In order to access the current challenges and submit predictions for CAGI, please register at https://genomeinterpretation.org/. Registered users also have access to presentations from the previous CAGI conferences, as well as posters and talk slides that summarize the results. Sincerely, Daniel Barsky, CAGI 2012 Organizer Steven E. Brenner, CAGI Chair John Moult, CAGI Chair cagi@genomeinterpretation.org