Showing papers by "Zhengdong D. Zhang published in 2012"
01 Sep 2012
TL;DR: The Encyclopedia of DNA Elements project provides new insights into the organization and regulation of the authors' genes and genome, and is an expansive resource of functional annotations for biomedical research.
2,767 citations
Wellcome Trust Sanger Institute1, University of Sydney2, Yale University3, University of Chicago4, University of Geneva5, Stanford University6, University of Cambridge7, Albert Einstein College of Medicine8, Washington University in St. Louis9, University of Oxford10, Beijing Institute of Genomics11, Broad Institute12, Harvard University13, Rutgers University14, Leiden University15, Cardiff University16, Baylor College of Medicine17
TL;DR: Functional and evolutionary differences between LoF-tolerant and recessive disease genes and a method for using these differences to prioritize candidate genes found in clinical sequencing studies are described.
Abstract: Genome-sequencing studies indicate that all humans carry many genetic variants predicted to cause loss of function (LoF) of protein-coding genes, suggesting unexpected redundancy in the human genome. Here we apply stringent filters to 2951 putative LoF variants obtained from 185 human genomes to determine their true prevalence and properties. We estimate that human genomes typically contain ~100 genuine LoF variants with ~20 genes completely inactivated. We identify rare and likely deleterious LoF alleles, including 26 known and 21 predicted severe disease-causing variants, as well as common LoF variants in nonessential genes. We describe functional and evolutionary differences between LoF-tolerant and recessive disease genes and a method for using these differences to prioritize candidate genes found in clinical sequencing studies.
1,186 citations
TL;DR: The existing WASP system, its proposed middleware role, and its planned interaction with XSEDE to form the Einstein Genome Gateway are discussed.
Abstract: Massively-parallel sequencing (MPS) technologies and their diverse applications in genomics and epigenomics research have yielded enormous new insights into the physiology and pathophysiology of the human genome. The biggest hurdle remains the magnitude and diversity of the datasets generated, compromising our ability to manage, organize, process and ultimately analyse data. The Wiki-based Automated Sequence Processor (WASP), developed at the Albert Einstein College of Medicine (hereafter Einstein), uniquely manages to tightly couple the sequencing platform, the sequencing assay, sample metadata and the automated workflows deployed on a heterogeneous high performance computing cluster infrastructure that yield sequenced, quality-controlled and 'mapped' sequence data, all within the one operating environment accessible by a web-based GUI interface. WASP at Einstein processes 4-6 TB of data per week and since its production cycle commenced it has processed ~ 1 PB of data overall and has revolutionized user interactivity with these new genomic technologies, who remain blissfully unaware of the data storage, management and most importantly processing services they request. The abstraction of such computational complexity for the user in effect makes WASP an ideal middleware solution, and an appropriate basis for the development of a grid-enabled resource - the Einstein Genome Gateway - as part of the Extreme Science and Engineering Discovery Environment (XSEDE) program. In this paper we discuss the existing WASP system, its proposed middleware role, and its planned interaction with XSEDE to form the Einstein Genome Gateway.
5 citations