DAVID bioinformatics resources consists of an integrated biological knowledgebase and analytic tools aimed at systematically extracting biological meaning from large gene/protein lists. This protocol explains how to use DAVID, a high-throughput and integrated data-mining environment, to analyze gene lists derived from high-throughput genomic experiments. The procedure first requires uploading a gene list containing any number of common gene identifiers followed by analysis using one or more text and pathway-mining tools such as gene functional classification, functional annotation chart or clustering and functional annotation table. By following this protocol, investigators are able to gain an in-depth understanding of the biological themes in lists of genes that are enriched in genome-scale studies.

http://dmrocke.ucdavis.edu/Class/BST226.2014.Winter/Nature%20Protocols%20DAVID.pdf

Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources.

Functional analysis of large gene lists, derived in most cases from emerging high-throughput genomic, proteomic and bioinformatics scanning approaches, is still a challenging and daunting task. The gene-annotation enrichment analysis is a promising high-throughput strategy that increases the likelihood for investigators to identify biological processes most pertinent to their study. Approximately 68 bioinformatics enrichment tools that are currently available in the community are collected in this survey. Tools are uniquely categorized into three major classes, according to their underlying enrichment algorithms. The comprehensive collections, unique tool classifications and associated questions/issues will provide a more comprehensive and up-to-date view regarding the advantages, pitfalls and recent trends in a simpler tool-class level rather than by a tool-by-tool approach. Thus, the survey will help tool designers/developers and experienced end users understand the underlying algorithms and pertinent details of particular tool categories/tools, enabling them to make the best choices for their particular research interests.

/pdf/bioinformatics-enrichment-tools-paths-toward-the-2yo1xl3r2j.pdf

Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists

Outcomes of high-throughput biological experiments are typically interpreted by statistical testing for enriched gene functional categories defined by the Gene Ontology (GO). The resulting lists of GO terms may be large and highly redundant, and thus difficult to interpret.

REVIGO is a Web server that summarizes long, unintelligible lists of GO terms by finding a representative subset of the terms using a simple clustering algorithm that relies on semantic similarity measures. Furthermore, REVIGO visualizes this non-redundant GO term set in multiple ways to assist in interpretation: multidimensional scaling and graph-based visualizations accurately render the subdivisions and the semantic relationships in the data, while treemaps and tag clouds are also offered as alternative views. REVIGO is freely available at http://revigo.irb.hr/.

/pdf/revigo-summarizes-and-visualizes-long-lists-of-gene-ontology-3taarmiz8n.pdf

REVIGO Summarizes and Visualizes Long Lists of Gene Ontology Terms

Fibrosis is defined by the overgrowth, hardening, and/or scarring of various tissues and is attributed to excess deposition of extracellular matrix components including collagen. Fibrosis is the end result of chronic inflammatory reactions induced by a variety of stimuli including persistent infections, autoimmune reactions, allergic responses, chemical insults, radiation, and tissue injury. Although current treatments for fibrotic diseases such as idiopathic pulmonary fibrosis, liver cirrhosis, systemic sclerosis, progressive kidney disease, and cardiovascular fibrosis typically target the inflammatory response, there is accumulating evidence that the mechanisms driving fibrogenesis are distinct from those regulating inflammation. In fact, some studies have suggested that ongoing inflammation is needed to reverse established and progressive fibrosis. The key cellular mediator of fibrosis is the myofibroblast, which when activated serves as the primary collagen-producing cell. Myofibroblasts are generated from a variety of sources including resident mesenchymal cells, epithelial and endothelial cells in processes termed epithelial/endothelial-mesenchymal (EMT/EndMT) transition, as well as from circulating fibroblast-like cells called fibrocytes that are derived from bone-marrow stem cells. Myofibroblasts are activated by a variety of mechanisms, including paracrine signals derived from lymphocytes and macrophages, autocrine factors secreted by myofibroblasts, and pathogen-associated molecular patterns (PAMPS) produced by pathogenic organisms that interact with pattern recognition receptors (i.e. TLRs) on fibroblasts. Cytokines (IL-13, IL-21, TGF-beta1), chemokines (MCP-1, MIP-1beta), angiogenic factors (VEGF), growth factors (PDGF), peroxisome proliferator-activated receptors (PPARs), acute phase proteins (SAP), caspases, and components of the renin-angiotensin-aldosterone system (ANG II) have been identified as important regulators of fibrosis and are being investigated as potential targets of antifibrotic drugs. This review explores our current understanding of the cellular and molecular mechanisms of fibrogenesis.

/pdf/cellular-and-molecular-mechanisms-of-fibrosis-48v3c6itoz.pdf

Cellular and molecular mechanisms of fibrosis.

The DAVID Gene Functional Classification Tool http://david.abcc.ncifcrf.gov uses a novel agglomeration algorithm to condense a list of genes or associated biological terms into organized classes of related genes or biology, called biological modules. This organization is accomplished by mining the complex biological co-occurrences found in multiple sources of functional annotation. It is a powerful method to group functionally related genes and terms into a manageable number of biological modules for efficient interpretation of gene lists in a network context.

/pdf/the-david-gene-functional-classification-tool-a-novel-3uns3hqi8x.pdf

The DAVID Gene Functional Classification Tool: a novel biological module-centric algorithm to functionally analyze large gene lists

We previously developed GoMiner, an application that organizes lists of 'interesting' genes (for example, under-and overexpressed genes from a microarray experiment) for biological interpretation in the context of the Gene Ontology. The original version of GoMiner was oriented toward visualization and interpretation of the results from a single microarray (or other high-throughput experimental platform), using a graphical user interface. Although that version can be used to examine the results from a number of microarrays one at a time, that is a rather tedious task, and original GoMiner includes no apparatus for obtaining a global picture of results from an experiment that consists of multiple microarrays. We wanted to provide a computational resource that automates the analysis of multiple microarrays and then integrates the results across all of them in useful exportable output files and visualizations.

/pdf/high-throughput-gominer-an-industrial-strength-integrative-nh278slt0z.pdf

High-Throughput GoMiner, an 'industrial-strength' integrative gene ontology tool for interpretation of multiple-microarray experiments, with application to studies of Common Variable Immune Deficiency (CVID)

Purpose of review Extensive research on molecular genetics in recent decades has provided a wealth of information about the mechanisms of primary immunodeficiency diseases. Microarray technology enables the survey of the expression of thousands of genes simultaneously. This review focuses on the commonly used arrays and initial applications in the study of primary immunodeficiency diseases. The application of this technology has been found to accelerate the discovery rate of gene expression disturbances in primary immunodeficiency diseases and provide potential molecular diagnostic tools. Recent findings The important role of microarray technology in functional genomic study has been demonstrated by the exponential growth in the number of scientific publications in the last few years. Microarray analysis has been used to study gene expression in several immunodeficiency diseases with known gene mutations as well as those with unknown causes. It has provided snapshots of gene expression and has presented the molecular phenotypes in the cells at defined times and under certain stimulation conditions. Studies comparing differential gene expression in patients and normal controls have allowed us to better understand the immunodeficiencies at the molecular level. Summary Application of microarray technology in immunodeficiency study has facilitated tracking the expression of thousands of genes simultaneously. The molecular phenotypes obtained from microarray results can be used in diagnosis of diseases, supplemental to clinical phenotypes. It is a powerful survey tool that can detect disturbed gene expression in immunodeficiency diseases, which will provide clues for disease gene discovery and potential targets for drug development.

Haiying Qin

Papers

High-Throughput GoMiner, an 'industrial-strength' integrative gene ontology tool for interpretation of multiple-microarray experiments, with application to studies of Common Variable Immune Deficiency (CVID)

Tracking gene expression in primary immunodeficiencies