Abstract
Summary
igv.js is an embeddable JavaScript implementation of the Integrative Genomics Viewer (IGV). It can be easily dropped into any web page with a single line of code and has no external ...dependencies. The viewer runs completely in the web browser, with no backend server and no data pre-processing required.
Availability and implementation
The igv.js JavaScript component can be installed from NPM at https://www.npmjs.com/package/igv. The source code is available at https://github.com/igvteam/igv.js under the MIT open-source license. IGV-Web, the end-user application built around igv.js, is available at https://igv.org/app. The source code is available at https://github.com/igvteam/igv-webapp under the MIT open-source license.
Supplementary information
Supplementary information is available at Bioinformatics online.
Accessible Reproducible Research Mesirov, Jill P.
Science (American Association for the Advancement of Science),
01/2010, Letnik:
327, Številka:
5964
Journal Article
Recenzirano
Odprti dostop
Scientific publications have at least two goals: (i) to announce a result and (ii) to convince readers that the result is correct. Mathematics papers are expected to contain a proof complete enough ...to allow knowledgeable readers to fill in any details. Papers in experimental science should describe the results and provide a clear enough protocol to allow successful repetition and extension.
The Molecular Signatures Database (MSigDB) is one of the most widely used and comprehensive databases of gene sets for performing gene set enrichment analysis. Since its creation, MSigDB has grown ...beyond its roots in metabolic disease and cancer to include >10,000 gene sets. These better represent a wider range of biological processes and diseases, but the utility of the database is reduced by increased redundancy across, and heterogeneity within, gene sets. To address this challenge, here we use a combination of automated approaches and expert curation to develop a collection of “hallmark” gene sets as part of MSigDB. Each hallmark in this collection consists of a “refined” gene set, derived from multiple “founder” sets, that conveys a specific biological state or process and displays coherent expression. The hallmarks effectively summarize most of the relevant information of the original founder sets and, by reducing both variation and redundancy, provide more refined and concise inputs for gene set enrichment analysis.
Display omitted
•We generate 50 “hallmark” gene sets from the Molecular Signature Database (MSigDB)•This required a hybrid approach combining computation with manual expert curation•The hallmarks reduce redundancy and produce more robust enrichment analysis results•We plan to move forward with a program to enhance and expand the hallmarks collection
Through extensive automated and manual curation, Liberzon et al. provide a refined and concise collection of “hallmark” gene sets from the Molecular Signatures Database for gene set enrichment analysis.
Manual review of aligned reads for confirmation and interpretation of variant calls is an important step in many variant calling pipelines for next-generation sequencing (NGS) data. Visual inspection ...can greatly increase the confidence in calls, reduce the risk of false positives, and help characterize complex events. The Integrative Genomics Viewer (IGV) was one of the first tools to provide NGS data visualization, and it currently provides a rich set of tools for inspection, validation, and interpretation of NGS datasets, as well as other types of genomic data. Here, we present a short overview of IGV's variant review features for both single-nucleotide variants and structural variants, with examples from both cancer and germline datasets. IGV is freely available at https://www.igv.org
.
Well-annotated gene sets representing the universe of the biological processes are critical for meaningful and insightful interpretation of large-scale genomic data. The Molecular Signatures Database ...(MSigDB) is one of the most widely used repositories of such sets.
We report the availability of a new version of the database, MSigDB 3.0, with over 6700 gene sets, a complete revision of the collection of canonical pathways and experimental signatures from publications, enhanced annotations and upgrades to the web site.
MSigDB is freely available for non-commercial use at http://www.broadinstitute.org/msigdb.
Gene-expression profiling has become a mainstay in immunology, but subtle changes in gene networks related to biological processes are hard to discern when comparing various datasets. For instance, ...conservation of the transcriptional response to sepsis in mouse models and human disease remains controversial. To improve transcriptional analysis in immunology, we created ImmuneSigDB: a manually annotated compendium of ∼5,000 gene-sets from diverse cell states, experimental manipulations, and genetic perturbations in immunology. Analysis using ImmuneSigDB identified signatures induced in activated myeloid cells and differentiating lymphocytes that were highly conserved between humans and mice. Sepsis triggered conserved patterns of gene expression in humans and mouse models. However, we also identified species-specific biological processes in the sepsis transcriptional response: although both species upregulated phagocytosis-related genes, a mitosis signature was specific to humans. ImmuneSigDB enables granular analysis of transcriptomic data to improve biological understanding of immune processes of the human and mouse immune systems.
Display omitted
•ImmuneSigDB: Collection of ∼5,000 gene sets derived from ∼400 immunological studies•Includes a wide range of mouse and human immune cell states and perturbations•Designed for use with GSEA and an approach called Leading Edge Metagene analysis•ImmuneSigDB identified shared and unique biology in human and mouse sepsis response
Meaningful interpretation of gene-expression analyses relies on identifying changes in expression of sets of genes corresponding to specific biological processes and cell states. Haining and colleagues generated a collection of ∼5,000 annotated, immunology-specific gene sets and uncovered shared and species-specific biology in mouse and human transcriptional responses to sepsis.
Data visualization is an essential component of genomic data analysis. However, the size and diversity of the data sets produced by today's sequencing and array-based profiling methods present major ...challenges to visualization tools. The Integrative Genomics Viewer (IGV) is a high-performance viewer that efficiently handles large heterogeneous data sets, while providing a smooth and intuitive user experience at all levels of genome resolution. A key characteristic of IGV is its focus on the integrative nature of genomic studies, with support for both array-based and next-generation sequencing data, and the integration of clinical and phenotypic data. Although IGV is often used to view genomic data from public sources, its primary emphasis is to support researchers who wish to visualize and explore their own data sets or those from colleagues. To that end, IGV supports flexible loading of local and remote data sets, and is optimized to provide high-performance data visualization and exploration on standard desktop systems. IGV is freely available for download from http://www.broadinstitute.org/igv, under a GNU LGPL open-source license.
Wnt/β-catenin signaling plays a key role in the pathogenesis of colon and other cancers; emerging evidence indicates that oncogenic β-catenin regulates several biological processes essential for ...cancer initiation and progression. To decipher the role of β-catenin in transformation, we classified β-catenin activity in 85 cancer cell lines in which we performed genome-scale loss-of-function screens and found that β-catenin active cancers are dependent on a signaling pathway involving the transcriptional regulator YAP1. Specifically, we found that YAP1 and the transcription factor TBX5 form a complex with β-catenin. Phosphorylation of YAP1 by the tyrosine kinase YES1 leads to localization of this complex to the promoters of antiapoptotic genes, including BCL2L1 and BIRC5. A small-molecule inhibitor of YES1 impeded the proliferation of β-catenin-dependent cancers in both cell lines and animal models. These observations define a β-catenin-YAP1-TBX5 complex essential to the transformation and survival of β-catenin-driven cancers.
Display omitted
► β-catenin-dependent cancers require YAP1 expression for survival ► β-catenin, YAP1, and TBX5 form a complex that drives expression of BIRC5 and BCL2L1 ► YES1 regulates the activity of the β-catenin-YAP1-TBX5 complex ► The YES1 inhibitor dasatinib inhibits the proliferation of β-catenin-active cells
Loss-of-function screens and β-catenin activity profiling in 85 cancer cell lines identified a transcriptional complex composed of YAP1, a known mediator of Hippo signaling, the transcription factor TBX5, and β-catenin. This complex is essential for the proliferation and tumorigenicity of β-catenin-active cell lines.
RNA has the intrinsic property to base pair, forming complex structures fundamental to its diverse functions. Here, we develop PARIS, a method based on reversible psoralen crosslinking for global ...mapping of RNA duplexes with near base-pair resolution in living cells. PARIS analysis in three human and mouse cell types reveals frequent long-range structures, higher-order architectures, and RNA-RNA interactions in trans across the transcriptome. PARIS determines base-pairing interactions on an individual-molecule level, revealing pervasive alternative conformations. We used PARIS-determined helices to guide phylogenetic analysis of RNA structures and discovered conserved long-range and alternative structures. XIST, a long noncoding RNA (lncRNA) essential for X chromosome inactivation, folds into evolutionarily conserved RNA structural domains that span many kilobases. XIST A-repeat forms complex inter-repeat duplexes that nucleate higher-order assembly of the key epigenetic silencing protein SPEN. PARIS is a generally applicable and versatile method that provides novel insights into the RNA structurome and interactome.
Display omitted
Display omitted
•PARIS yields in vivo RNA duplex maps of human and mouse cells.•In vivo maps discover extensive long-range and alternative RNA structures.•PARIS guides evolution analysis and validation of duplex function.•Unique duplex fold of XIST A-repeat nucleates XIST-SPEN lncRNP.
A method for global mapping of RNA duplexes in living cells with near base-pair resolution, called PARIS, reveals extensive long-range structures, higher-order architectures, alternative structures, and RNA-RNA interactions across the transcriptome and uncovers a unique architecture of Xist and its specific interaction with a key silencing factor.
Gene Set Enrichment Analysis (GSEA) is a computational method that assesses whether an a priori defined set of genes shows statistically significant, concordant differences between two biological ...states. We report the availability of a new version of the Java based software (GSEA-P 2.0) that represents a major improvement on the previous release through the addition of a leading edge analysis component, seamless integration with the Molecular Signature Database (MSigDB) and an embedded browser that allows users to search for gene sets and map them to a variety of microarray platform formats. This functionality makes it possible for users to directly import gene sets from MSigDB for analysis with GSEA. We have also improved the visualizations in GSEA-P 2.0 and added links to a new form of concise gene set annotations called Gene Set Cards. These additions, as well as other improvements suggested by over 3500 users who have downloaded the software over the past year have been incorporated into this new release of the GSEA-P Java desktop program. Availability: GSEA-P 2.0 is freely available for academic and commercial users and can be downloaded from http://www.broad.mit.edu/GSEA Contact: mesirov@broad.mit.edu Supplementary information: Supplementary data are available at Bioinformatics online.
PDF
