AnGeLi: A Tool for the Analysis of Gene Lists from Fission Yeast

Abstract

Genome-wide assays and screens typically result in large lists of genes or proteins. Enrichments of functional or other biological properties within such lists can provide valuable insights and testable hypotheses. To systematically detect these enrichments can be challenging and time-consuming, because relevant data to compare against query gene lists are spread over many different sources. We have developed AnGeLi (Analysis of Gene Lists), an intuitive, integrated web-tool for comprehensive and customized interrogation of gene lists from the fission yeast, Schizosaccharomyces pombe. AnGeLi searches for significant enrichments among multiple qualitative and quantitative information sources, including gene and phenotype ontologies, genetic and protein interactions, numerous features of genes, transcripts, translation, and proteins such as copy numbers, chromosomal positions, genetic diversity, RNA polymerase II and ribosome occupancy, localization, conservation, half-lives, domains, and molecular weight among others, as well as diverse sets of genes that are co-regulated or lead to the same phenotypes when mutated. AnGeLi uses robust statistics which can be tailored to specific needs. It also provides the option to upload user-defined gene sets to compare against the query list. Through an integrated data submission form, AnGeLi encourages the community to contribute additional curated gene lists to further increase the usefulness of this resource and to get the most from the ever increasing large-scale experiments. AnGeLi offers a rigorous yet flexible statistical analysis platform for rich insights into functional enrichments and biological context for query gene lists, thus providing a powerful exploratory tool through which S. pombe researchers can uncover fresh perspectives and unexpected connections from genomic data. AnGeLi is freely available at: www.bahlerlab.info/AnGeLi.

Keywords: PomBase; S. pombe; data mining; database; gene cluster; genetic screen; large-scale assay; ontology.

FIGURE 1

Workflows in AnGeLi. (Top – blue) Data entry: the user pastes a query gene list and has the option to add user-defined gene sets and/or select the background gene set (default = PC; protein-coding genes). If no additional gene sets are added, under default settings, 7554 features of the AnGeLi knowledgebase will be analyzed (7505 binary, and 49 metric features), because 1277 GO Molecular Function, 797 GO Cellular Component, and 4 Genetic and Physical Interactions (BioGRID) features are excluded by default (9632 features in total). If any user-defined gene sets are added, the database is augmented accordingly. (Middle – green) Statistical parameter settings: the user selects GO category (default = BP; Biological Process), a method for multiple testing correction (default = FDR) and the desired p-value threshold (default = 0.01). The users can also specify whether to perform the pairwise interaction enrichment analysis (default = No), set the desired number of permutations accordingly (default = 1000), and adjust the p-value to account for multiple testing. (Bottom – red) Data processing: AnGeLi performs gene list enrichment analysis based on user input and reports any significant functional enriched features, along with associated information.