Institute for Systems Biology

About: Institute for Systems Biology is a nonprofit organization based out in Seattle, Washington, United States. It is known for research contribution in the topics: Population & Proteomics. The organization has 1277 authors who have published 2777 publications receiving 353165 citations.

RCytoscape: tools for exploratory network analysis

Abstract: Background: Biomolecular pathways and networks are dynamic and complex, and the perturbations to them which cause disease are often multiple, heterogeneous and contingent. Pathway and network visualizations, rendered on a computer or published on paper, however, tend to be static, lacking in detail, and ill-equipped to explore the variety and quantities of data available today, and the complex causes we seek to understand. Results: RCytoscape integrates R (an open-ended programming environment rich in statistical power and datahandling facilities) and Cytoscape (powerful network visualization and analysis software). RCytoscape extends Cytoscape's functionality beyond what is possible with the Cytoscape graphical user interface. To illustrate the power of RCytoscape, a portion of the Glioblastoma multiforme (GBM) data set from the Cancer Genome Atlas (TCGA) is examined. Network visualization reveals previously unreported patterns in the data suggesting heterogeneous signaling mechanisms active in GBM Proneural tumors, with possible clinical relevance. Conclusions: Progress in bioinformatics and computational biology depends upon exploratory and confirmatory data analysis, upon inference, and upon modeling. These activities will eventually permit the prediction and control of complex biological systems. Network visualizations -- molecular maps -- created from an open-ended programming environment rich in statistical power and data-handling facilities, such as RCytoscape, will play an essential role in this progression.

POSaM: a fast, flexible, open-source, inkjet oligonucleotide synthesizer and microarrayer.

Abstract: DNA arrays are valuable tools in molecular biology laboratories Their rapid acceptance was aided by the release of plans for a pin-spotting microarrayer by researchers at Stanford Inkjet microarraying is a flexible, complementary technique that allows the synthesis of arrays of any oligonucleotide sequences de novo We describe here an open-source inkjet arrayer capable of rapidly producing sets of unique 9,800-feature arrays

A unified test of linkage analysis and rare-variant association for analysis of pedigree sequence data

Abstract: High-throughput sequencing of related individuals has become an important tool for studying human disease. However, owing to technical complexity and lack of available tools, most pedigree-based sequencing studies rely on an ad hoc combination of suboptimal analyses. Here we present pedigree-VAAST (pVAAST), a disease-gene identification tool designed for high-throughput sequence data in pedigrees. pVAAST uses a sequence-based model to perform variant and gene-based linkage analysis. Linkage information is then combined with functional prediction and rare variant case-control association information in a unified statistical framework. pVAAST outperformed linkage and rare-variant association tests in simulations and identified disease-causing genes from whole-genome sequence data in three human pedigrees with dominant, recessive and de novo inheritance patterns. The approach is robust to incomplete penetrance and locus heterogeneity and is applicable to a wide variety of genetic traits. pVAAST maintains high power across studies of monogenic, high-penetrance phenotypes in a single pedigree to highly polygenic, common phenotypes involving hundreds of pedigrees.

Simvastatin augments lipopolysaccharide-induced proinflammatory responses in macrophages by differential regulation of the c-Fos and c-Jun transcription factors.

Abstract: The 3-hydroxyl-3-methylglutaryl-coenzyme A reductase inhibitors, or statins, are a widely used class of drugs for cholesterol reduction. The reduction in mortality and morbidity in statin-treated patients is incompletely explained by their effects on cholesterol, and an anti-inflammatory role for the drug has been proposed. We report in this work that, unexpectedly, simvastatin enhances LPS-induced IL-12p40 production by murine macrophages, and that it does so by activating the IL-12p40 promoter. Mutational analysis and dominant-negative expression studies indicate that both C/EBP and AP-1 transcription factors have a crucial role in promoter activation. This occurs via a c-Fos- and c-Jun-based mechanism; we demonstrate that ectopic expression of c-Jun activates the IL-12p40 promoter, whereas expression of c-Fos inhibits IL-12p40 promoter activity. Simvastatin prevents LPS-induced c-Fos expression, thereby relieving the inhibitory effect of c-Fos on the IL-12p40 promoter. Concomitantly, simvastatin induces the phosphorylation of c-Jun by the c-Jun N-terminal kinase, resulting in c-Jun-dependent activation of the IL-12p40 promoter. This appears to be a general mechanism because simvastatin also augments LPS-dependent activation of the TNF-α promoter, perhaps because the TNF-α promoter has C/EBP and AP-1 binding sites in a similar configuration to the IL-12p40 promoter. The fact that simvastatin potently augments LPS-induced IL-12p40 and TNF-α production has implications for the treatment of bacterial infections in statin-treated patients.