Cytoscape: the network visualization tool for GenomeSpace workflows.

Modern genomic analysis often requires workflows incorporating multiple best-of-breed tools. GenomeSpace is a web-based visual workbench that combines a selection of these tools with mechanisms that create data flows between them. One such tool is Cytoscape 3, a popular application that enables analysis and visualization of graph-oriented genomic networks. As Cytoscape runs on the desktop, and not in a web browser, integrating it into GenomeSpace required special care in creating a seamless user experience and enabling appropriate data flows. In this paper, we present the design and operation of the Cytoscape GenomeSpace app, which accomplishes this integration, thereby providing critical analysis and visualization functionality for GenomeSpace users. It has been downloaded over 850 times since the release of its first version in September, 2013

Ethics in Dangerous Situations

To protect soldiers repairing a vehicle on a road, a platoon leader in Iraq provided protection for them by positioning two manned vehicles along possible routes that other vehicles, potentially laden with explosives, could use. In doing so, he decided not to follow the platoon\u27s standard operating procedure (SOP), which called for controlling traffic along the road by separating nonthreatening Iraqi vehicles from suspicious ones. He believed that he was being paid to exercise judgment, so he broke from routine. Because he knew the enemy had used snipers against soldiers on this road in the past, he calculated that the risk of them doing so again far outweighed the potential of firing on nonthreatening Iraqi vehicles because of a failure to control the traffic. Soon after getting their vehicles in position, the soldiers saw a sedan speeding toward their position. As it got closer, the platoon leader ordered one of his soldiers to fire a warning shot, after which the sedan sped up. Thinking they were in imminent danger, the soldiers trained their fire on the sedan and braced for an explosion. The sedan skidded to a stop less than five meters from the soldiers, and they soon discovered that they had killed an elderly man with thick glasses and hearing aids in both ears. When the battalion executive officer reviewed the platoon\u27s actions, he agreed with the lieutenant\u27s decision to deviate from routine and not put soldiers on the road, affirmed that the soldiers did the right thing, and called the killing of the elderly man a terrible tragedy of war

Ethics in Dangerous Situations

To protect soldiers repairing a vehicle on a road, a platoon leader in Iraq provided protection for them by positioning two manned vehicles along possible routes that other vehicles, potentially laden with explosives, could use. In doing so, he decided not to follow the platoon\u27s standard operating procedure (SOP), which called for controlling traffic along the road by separating nonthreatening Iraqi vehicles from suspicious ones. He believed that he was being paid to exercise judgment, so he broke from routine. Because he knew the enemy had used snipers against soldiers on this road in the past, he calculated that the risk of them doing so again far outweighed the potential of firing on nonthreatening Iraqi vehicles because of a failure to control the traffic. Soon after getting their vehicles in position, the soldiers saw a sedan speeding toward their position. As it got closer, the platoon leader ordered one of his soldiers to fire a warning shot, after which the sedan sped up. Thinking they were in imminent danger, the soldiers trained their fire on the sedan and braced for an explosion. The sedan skidded to a stop less than five meters from the soldiers, and they soon discovered that they had killed an elderly man with thick glasses and hearing aids in both ears. When the battalion executive officer reviewed the platoon\u27s actions, he agreed with the lieutenant\u27s decision to deviate from routine and not put soldiers on the road, affirmed that the soldiers did the right thing, and called the killing of the elderly man a terrible tragedy of war

Computational Knowledge Integration in Biopharmaceutical Research

An initiative to increase biopharmaceutical research productivity by capturing, sharing and computationally integrating proprietary scientific discoveries with public knowledge is described. This initiative involves both organisational process change and multiple interoperating software systems. The software components rely on mutually supporting integration techniques. These include a richly structured ontology, statistical analysis of experimental data against stored conclusions, natural language processing of public literature, secure document repositories with lightweight metadata, web services integration, enterprise web portals and relational databases. This approach has already begun to increase scientific productivity in our enterprise by creating an organisational memory (OM) of internal research findings, accessible on the web. Through bringing together these components it has also been possible to construct a very large and expanding repository of biological pathway information linked to this repository of findings which is extremely useful in analysis of DNA microarray data. This repository, in turn, enables our research paradigm to be shifted towards more comprehensive systems-based understandings of drug action

MHC Haplotype Matching for Unrelated Hematopoietic Cell Transplantation

BACKGROUND: Current criteria for the selection of unrelated donors for hematopoietic cell transplantation (HCT) include matching for the alleles of each human leukocyte antigen (HLA) locus within the major histocompatibility complex (MHC). Graft-versus-host disease (GVHD), however, remains a significant and potentially life-threatening complication even after HLA-identical unrelated HCT. The MHC harbors more than 400 genes, but the total number of transplantation antigens is unknown. Genes that influence transplantation outcome could be identified by using linkage disequilibrium (LD)-mapping approaches, if the extended MHC haplotypes of the unrelated donor and recipient could be defined. METHODS AND FINDINGS: We isolated DNA strands extending across 2 million base pairs of the MHC to determine the physical linkage of HLA-A, -B, and -DRB1 alleles in 246 HCT recipients and their HLA-A, -B, -C, -DRB1, -DQB1 allele-matched unrelated donors. MHC haplotype mismatching was associated with a statistically significantly increased risk of severe acute GVHD (odds ratio 4.51; 95% confidence interval [CI], 2.34–8.70, p < 0.0001) and with lower risk of disease recurrence (hazard ratio 0.45; 95% CI, 0.22–0.92, p = 0.03). CONCLUSIONS: The MHC harbors genes that encode unidentified transplantation antigens. The three-locus HLA-A, -B, -DRB1 haplotype serves as a proxy for GVHD risk among HLA-identical transplant recipients. The phasing method provides an approach for mapping novel MHC-linked transplantation determinants and a means to decrease GVHD-related morbidity after HCT from unrelated donors

Integrative genomic analysis by interoperation of bioinformatics tools in GenomeSpace

Integrative analysis of multiple data types to address complex biomedical questions requires the use of multiple software tools in concert and remains an enormous challenge for most of the biomedical research community. Here we introduce GenomeSpace (http://www.genomespace.org), a cloud-based, cooperative community resource. Seeded as a collaboration of six of the most popular genomics analysis tools, GenomeSpace now supports the streamlined interaction of 20 bioinformatics tools and data resources. To facilitate the ability of non-programming users’ to leverage GenomeSpace in integrative analysis, it offers a growing set of ‘recipes’, short workflows involving a few tools and steps to guide investigators through high utility analysis tasks

The HLA–DRB1 shared epitope is associated with susceptibility to rheumatoid arthritis in African Americans through European genetic admixture

To determine whether shared epitope (SE)–containing HLA–DRB1 alleles are associated with rheumatoid arthritis (RA) in African Americans and whether their presence is associated with higher degrees of global (genome-wide) genetic admixture from the European population

The landscape of somatic copy-number alteration across human cancers

available in PMC 2010 August 18.A powerful way to discover key genes with causal roles in oncogenesis is to identify genomic regions that undergo frequent alteration in human cancers. Here we present high-resolution analyses of somatic copy-number alterations (SCNAs) from 3,131 cancer specimens, belonging largely to 26 histological types. We identify 158 regions of focal SCNA that are altered at significant frequency across several cancer types, of which 122 cannot be explained by the presence of a known cancer target gene located within these regions. Several gene families are enriched among these regions of focal SCNA, including the BCL2 family of apoptosis regulators and the NF-κΒ pathway. We show that cancer cells containing amplifications surrounding the MCL1 and BCL2L1 anti-apoptotic genes depend on the expression of these genes for survival. Finally, we demonstrate that a large majority of SCNAs identified in individual cancer types are present in several cancer types.National Institutes of Health (U.S.) (Dana-Farber/Harvard Cancer Center and Pacific Northwest Prostate Cancer SPOREs, P50CA90578)National Institutes of Health (U.S.) (Dana-Farber/Harvard Cancer Center and Pacific Northwest Prostate Cancer SPOREs, R01CA109038))National Institutes of Health (U.S.) (Dana-Farber/Harvard Cancer Center and Pacific Northwest Prostate Cancer SPOREs, R01CA109467)National Institutes of Health (U.S.) (Dana-Farber/Harvard Cancer Center and Pacific Northwest Prostate Cancer SPOREs, P01CA085859)National Institutes of Health (U.S.) (Dana-Farber/Harvard Cancer Center and Pacific Northwest Prostate Cancer SPOREs, P01CA 098101)National Institutes of Health (U.S.) (Dana-Farber/Harvard Cancer Center and Pacific Northwest Prostate Cancer SPOREs, K08CA122833