FLAME: A Web Tool for Functional and Literature Enrichment Analysis of Multiple Gene Lists.

Foteini Thanati,Dimitrios J Stravopodis,Aristides G Eliopoulos,Evangelos Karatzas,Georgios A Pavlopoulos,Fotis A Baltoumas

doi:10.3390/biology10070665

Abstract

Simple SummaryManipulation of multiple gene lists when going through a functional enrichment analysis is often a hefty task. In this article, we present FLAME, a web application that facilitates such multiple-list manipulations, enabling the construction of intersections and unions among multiple gene lists for further enrichment analysis. Reported results are presented via multiple interactive viewers such as heatmaps, barcharts, Manhattan plots, and networks.Functional enrichment is a widely used method for interpreting experimental results by identifying classes of proteins/genes associated with certain biological functions, pathways, diseases, or phenotypes. Despite the variety of existing tools, most of them can process a single list per time, thus making a more combinatorial analysis more complicated and prone to errors. In this article, we present FLAME, a web tool for combining multiple lists prior to enrichment analysis. Users can upload several lists and use interactive UpSet plots, as an alternative to Venn diagrams, to handle unions or intersections among the given input files. Functional and literature enrichment, along with gene conversions, are offered by g:Profiler and aGOtool applications for 197 organisms. FLAME can analyze genes/proteins for related articles, Gene Ontologies, pathways, annotations, regulatory motifs, domains, diseases, and phenotypes, and can also generate protein–protein interactions derived from STRING. We have validated FLAME by interrogating gene expression data associated with the sensitivity of the distal part of the large intestine to experimental colitis-propelled colon cancer. FLAME comes with an interactive user-friendly interface for easy list manipulation and exploration, while results can be visualized as interactive and parameterizable heatmaps, barcharts, Manhattan plots, networks, and tables.

Highlights

Functional enrichment analysis is a method to identify classes of bioentities in which genes or proteins have been found to be over-represented
We tested the capacity of FLAME for knowledge discovery by re-analyzing gene expression data associated with colitis-propelled carcinogenesis (CAC) in mice [51]
We identified 165 transcripts belonging to this intersection by using the ‘UpSet Plot’ option of FLAME (Figure 3A and Table S1), and termed this gene set ‘the susceptibility-associated gene signature’ (SAS)

Summary

Introduction

Functional enrichment analysis is a method to identify classes of bioentities in which genes or proteins have been found to be over-represented. This type of analysis can aid researchers to reveal biological insights from various omics experiments and interpret gene lists of interest in a biologically meaningful way. For this purpose, several applications have been proposed [1,2]. Most of them are offered as web applications, and among other functionalities, they associate overrepresented genes with GO terms [19], or pathways [20,21,22,23]. (a) they often differ in the organisms, the identifiers, and the backend database they support; (b) they come with their own way of reporting results (mostly lists or static representations); and (c) they are often unable to handle and compare multiple lists for a more combinatorial analysis

Methods

Results

Conclusion