n e Grid2003 Project has deployed a multi-virfual organization, application-driven grid laboratory ('"Grid3'7 that has sustained for several months the production-level services required by physics experiments of the Large Hadron Collider at CERN (ATLAS and CMS), the Sloan Digital Sky Survey project, the gravitational wave search experiment LIGO, the BTeV mperiment at Fermilab, as well as applications in molecular structure analysis and genome analysis, and computer science research projects in such areas as job and data scheduling. The deployed infiastmcture has been operating since Noisniber 2003 with 27 sites, apeak of 2800 processors, work loads fiom 10 different applications exceeding 1300 simultaneous jobs, and data transfers among sites of greater than 2 TBiday. We describe the principles that have guided the development of this unique infrastructure and the practical experiences that have resultedfiom its creation and use. We discuss application requirements for grid services deployment and con$guration. monitoring infiastnic fure, application performance, metrics. and operational experiences. We also summarize lessons learned.
BackgroundSingle nucleotide polymorphisms (SNPs) are the most abundant type of genetic variation in eukaryotic genomes and have recently become the marker of choice in a wide variety of ecological and evolutionary studies. The advent of next-generation sequencing (NGS) technologies has made it possible to efficiently genotype a large number of SNPs in the non-model organisms with no or limited genomic resources. Most NGS-based genotyping methods require a reference genome to perform accurate SNP calling. Little effort, however, has yet been devoted to developing or improving algorithms for accurate SNP calling in the absence of a reference genome.ResultsHere we describe an improved maximum likelihood (ML) algorithm called iML, which can achieve high genotyping accuracy for SNP calling in the non-model organisms without a reference genome. The iML algorithm incorporates the mixed Poisson/normal model to detect composite read clusters and can efficiently prevent incorrect SNP calls resulting from repetitive genomic regions. Through analysis of simulation and real sequencing datasets, we demonstrate that in comparison with ML or a threshold approach, iML can remarkably improve the accuracy of de novo SNP genotyping and is especially powerful for the reference-free genotyping in diploid genomes with high repeat contents.ConclusionsThe iML algorithm can efficiently prevent incorrect SNP calls resulting from repetitive genomic regions, and thus outperforms the original ML algorithm by achieving much higher genotyping accuracy. Our algorithm is therefore very useful for accurate de novo SNP genotyping in the non-model organisms without a reference genome.ReviewersThis article was reviewed by Dr. Richard Durbin, Dr. Liliana Florea (nominated by Dr. Steven Salzberg) and Dr. Arcady Mushegian.
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