Restring: managing functional enrichment of complex experimental designs made easy

Functional enrichment analysis is an analytical method to extract biological insights from gene expression data, popularized by the ever-growing application of high-throughput techniques. Typically, expression profiles are generated for hundreds to thousands of genes/proteins from samples belonging to two experimental groups, and after ad-hoc statistical tests, researchers are left with lists of statistically significant entities, possibly lacking any unifying biological theme. Functional enrichment tackles the problem of putting overall gene expression changes into a broader biological context, based on pre-existing knowledge bases of reference: database collections of known expression regulation, relationships and molecular interactions. STRING is among the most popular tools, providing both protein-protein interaction networks and functional enrichment analysis for any given set of identifiers. For complex experimental designs, manually retrieving, interpreting, analyzing and abridging functional enrichment results is a daunting task, usually performed by hand by the average wet-biology researcher. We have developed restring (https://github.com/Stemanz/ restring), a cross-platform, open-source software that seamlessly retrieves from STRING functional enrichments from multiple user-supplied gene sets, without any need for specific bioinformatics skills. As a core capability, it aggregates all such findings into human-readable table summaries, with built-in features to easily pro- duce user-customizable publication-grade clustermaps and bubble plots. Everything is managed through reString’s straightforward graphical user interface in just a few clicks and seconds of processing times. The software is backed with a comprehensive online documentation, YouTube installation tutorials, sample input files, online support, an upcoming publication and more.