GenMAPP 2: New features and resources for pathway analysis

BACKGROUND: Microarray technologies have evolved rapidly, enabling biologists to quantify genome-wide levels of gene expression, alternative splicing, and sequence variations for a variety of species. Analyzing and displaying these data present a significant challenge. Pathway-based approaches for analyzing microarray data have proven useful for presenting data and for generating testable hypotheses. RESULTS: To address the growing needs of the microarray community we have released version 2 of Gene Map Annotator and Pathway Profiler (GenMAPP), a new GenMAPP database schema, and integrated resources for pathway analysis. We have redesigned the GenMAPP database to support multiple gene annotations and species as well as custom species database creation for a potentially unlimited number of species. We have expanded our pathway resources by utilizing homology information to translate pathway content between species and extending existing pathways with data derived from conserved protein interactions and coexpression. We have implemented a new mode of data visualization to support analysis of complex data, including time-course, single nucleotide polymorphism (SNP), and splicing. GenMAPP version 2 also offers innovative ways to display and share data by incorporating HTML export of analyses for entire sets of pathways as organized web pages. CONCLUSION: GenMAPP version 2 provides a means to rapidly interrogate complex experimental data for pathway-level changes in a diverse range of organisms

CORNA: testing gene lists for regulation by microRNAs

Motivation: With the increasing use of post-genomics techniques to examine a wide variety of biological systems in laboratories throughout the world, scientists are often presented with lists of genes that they must make sense of. A consistently challenging problem is that of defining co-regulated genes within those gene lists. In recent years, microRNAs have emerged as a mechanism for regulating several cellular processes. In this article, we report on how gene lists and microRNA targets data may be integrated to test for significant associations between gene lists and microRNAs

WikiPathways: building research communities on biological pathways.

Here, we describe the development of WikiPathways (http://www.wikipathways.org), a public wiki for pathway curation, since it was first published in 2008. New features are discussed, as well as developments in the community of contributors. New features include a zoomable pathway viewer, support for pathway ontology annotations, the ability to mark pathways as private for a limited time and the availability of stable hyperlinks to pathways and the elements therein. WikiPathways content is freely available in a variety of formats such as the BioPAX standard, and the content is increasingly adopted by external databases and tools, including Wikipedia. A recent development is the use of WikiPathways as a staging ground for centrally curated databases such as Reactome. WikiPathways is seeing steady growth in the number of users, page views and edits for each pathway. To assess whether the community curation experiment can be considered successful, here we analyze the relation between use and contribution, which gives results in line with other wiki projects. The novel use of pathway pages as supplementary material to publications, as well as the addition of tailored content for research domains, is expected to stimulate growth further

Methods for interpreting lists of affected genes obstained in a DNA microarray experiment

Background - The aim of this paper was to describe and compare the methods used and the results obtained by the participants in a joint EADGENE (European Animal Disease Genomic Network of Excellence) and SABRE (Cutting Edge Genomics for Sustainable Animal Breeding) workshop focusing on post analysis of microarray data. The participating groups were provided with identical lists of microarray probes, including test statistics for three different contrasts, and the normalised log-ratios for each array, to be used as the starting point for interpreting the affected probes. The data originated from a microarray experiment conducted to study the host reactions in broilers occurring shortly after a secondary challenge with either a homologous or heterologous species of Eimeria. Results - Several conceptually different analytical approaches, using both commercial and public available software, were applied by the participating groups. The following tools were used: Ingenuity Pathway Analysis, MAPPFinder, LIMMA, GOstats, GOEAST, GOTM, Globaltest, TopGO, ArrayUnlock, Pathway Studio, GIST and AnnotationDbi. The main focus of the approaches was to utilise the relation between probes/genes and their gene ontology and pathways to interpret the affected probes/genes. The lack of a well-annotated chicken genome did though limit the possibilities to fully explore the tools. The main results from these analyses showed that the biological interpretation is highly dependent on the statistical method used but that some common biological conclusions could be reached. Conclusion - It is highly recommended to test different analytical methods on the same data set and compare the results to obtain a reliable biological interpretation of the affected genes in a DNA microarray experimen

Understanding cellular function and disease with comparative pathway analysis

Pathway analysis is important in interpreting the functional implications of high-throughput experimental results, but robust comparison across platforms and species is problematic. A new approach, Pathprinting, provides a cross-platform, cross-species comparative analysis of pathway expression signatures. This method calculates pathway-level statistics from gene expression across nearly 180,000 microarrays in the Gene Expression Omnibus. Pathprinting can accurately retrieve phenotypically similar samples and identify sets of human and mouse genes that are prognostic in cancer

Use of GenMAPP and MAPPFinder to analyse pathways involved in chickens infected with the protozoan parasite Eimeria

<p>Abstract</p> <p>Background</p> <p>Microarrays allow genome-wide assays of gene expression. There is a need for user-friendly software to visualise and analyse these data. Analysing microarray data in the context of biological pathways is now common, and several tools exist.</p> <p>Results</p> <p>We describe the use of MAPPFinder, a component of GenMAPP to characterise the biological pathways affected in chickens infected with the protozoan parasite <it>Eimeria. </it>Several pathways were significantly affected based on the unadjusted p-value, including several immune-system pathways.</p> <p>Conclusion</p> <p>GenMAPP/MAPPFinder provides a means to rapidly visualise pathways affected in microarray studies. However, it relies on good genome annotation and having genes reliably linked to pathway objects. We show that GenMAPP/MAPPFinder can produce useful results, and as the annotation of the chicken genome improves, so will the level of information gained.</p

Bioinformatic interrogation of expression array data to identify nutritionally regulated genes potentially modulated by DNA methylation

DNA methylation occurs at CpG dinucleotide sites within the genome and is recognised as one of the mechanisms involved in regulation of gene expression. CpG sites are relatively underrepresented in the mammalian genome, but occur densely in regions called CpG islands (CGIs). CGIs located in the promoters of genes inhibit transcription when methylated by impeding transcription factor binding. Due to the malleable nature of DNA methylation, environmental factors are able to influence promoter CGI methylation patterns and thus influence gene expression. Recent studies have provided evidence that nutrition (and other environmental exposures) can cause altered CGI methylation but, with a few exceptions, the genes influenced by these exposures remain largely unknown. Here we describe a novel bioinformatics approach for the analysis of gene expression microarray data designed to identify regulatory sites within promoters of differentially expressed genes that may be influenced by changes in DNA methylation

WikiPathways: Pathway Editing for the People

WikiPathways provides a collaborative platform for creating, updating, and sharing pathway diagrams and serves as an example of content curation by the biology community

Mining Biological Pathways Using WikiPathways Web Services

WikiPathways is a platform for creating, updating, and sharing biological pathways [1]. Pathways can be edited and downloaded using the wiki-style website. Here we present a SOAP web service that provides programmatic access to WikiPathways that is complementary to the website. We describe the functionality that this web service offers and discuss several use cases in detail. Exposing WikiPathways through a web service opens up new ways of utilizing pathway information and assisting the community curation process