MOTIVATION: The use of dense single nucleotide polymorphism (SNP) data in genetic linkage analysis of large pedigrees is impeded by significant technical, methodological and computational challenges. Here we describe Superlink-Online SNP, a new powerful online system that streamlines the linkage analysis of SNP data. It features a fully integrated flexible processing workflow comprising both well-known and novel data analysis tools, including SNP clustering, erroneous data filtering, exact and approximate LOD calculations and maximum-likelihood haplotyping. The system draws its power from thousands of CPUs, performing data analysis tasks orders of magnitude faster than a single computer. By providing an intuitive interface to sophisticated state-of-the-art analysis tools coupled with high computing capacity, Superlink-Online SNP helps geneticists unleash the potential of SNP data for detecting disease genes. RESULTS: Computations performed by Superlink-Online SNP are automatically parallelized using novel paradigms, and executed on unlimited number of private or public CPUs. One novel service is large-scale approximate Markov Chain-Monte Carlo (MCMC) analysis. The accuracy of the results is reliably estimated by running the same computation on multiple CPUs and evaluating the Gelman-Rubin Score to set aside unreliable results. Another service within the workflow is a novel parallelized exact algorithm for inferring maximum-likelihood haplotyping. The reported system enables genetic analyses that were previously infeasible. We demonstrate the system capabilities through a study of a large complex pedigree affected with metabolic syndrome. AVAILABILITY: Superlink-Online SNP is freely available for researchers at http://cbl-hap.cs.technion.ac.il/superlink-snp. The system source code can also be downloaded from the system website. CONTACT: [email protected] SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Vol. 29, No. 2, 2013, pp. 197–205 doi:10.1093/bioinformatics/bts658 The publishers regret that the author affiliations for this paper should appear as follows: Mark Silberstein1,2, Omer Weissbrod1,*, Lars Otten3, Anna Tzemach1, Andrei Anisenia1,4, Oren Shtark1, Dvir Tuberg1, Eddie Galfrin1, Irena Gannon1, Adel Shalata5,6,7, Zvi U. Borochowitz5,8, Rina Dechter3, Elizabeth Thompson9 and Dan Geiger1 1Department of Computer Science, Technion-Israel Institute of Technology, Haifa, Israel, 2Department of Computer Science, University of Texas at Austin, Austin, TX, USA, 3Donald Bren School of Information and Computer Sciences, UC Irvine, CA, USA, 4Department of Computer Science, University of Ottawa, Ottawa, Canada, 5The Simon Winter Institute for Human Genetics, Bnai-Zion Medical Center, Haifa, Israel, 6Research and Development Center, The Galilee Society, Shefa-Amr, Israel, 7Holy Family Hospital, Nazareth, Israel, 8The Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa, Israel and 9Department of Statistics, University of Washington, Seattle, WA, USA