RedRibbon: A new rank–rank hypergeometric overlap for gene and transcript expression signatures

Author:

Piron Anthony123ORCID,Szymczak Florian12,Papadopoulou Theodora12,Alvelos Maria Inês1,Defrance Matthieu23,Lenaerts Tom234,Eizirik Décio L1,Cnop Miriam15ORCID

Affiliation:

1. ULB Center for Diabetes Research, Medical Faculty, Université Libre de Bruxelles

2. Interuniversity Institute of Bioinformatics in Brussels (IB2), Brussels, Belgium

3. Machine Learning Group, Université Libre de Bruxelles

4. Artificial Intelligence Lab, Vrije Universiteit Brussel, Brussels, Belgium

5. Division of Endocrinology, Erasmus Hospital, Université Libre de Bruxelles

Abstract

High-throughput omics technologies have generated a wealth of large protein, gene, and transcript datasets that have exacerbated the need for new methods to analyse and compare big datasets. Rank–rank hypergeometric overlap is an important threshold-free method to combine and visualize two ranked lists ofP-values or fold-changes, usually from differential gene expression analyses. Here, we introduce a new rank–rank hypergeometric overlap-based method aimed at gene level and alternative splicing analyses at transcript or exon level, hitherto unreachable as transcript numbers are an order of magnitude larger than gene numbers. We tested the tool on synthetic and real datasets at gene and transcript levels to detect correlation and anticorrelation patterns and found it to be fast and accurate, even on very large datasets thanks to an evolutionary algorithm-based minimalP-value search. The tool comes with a ready-to-use permutation scheme allowing the computation of adjustedP-values at low time cost. The package compatibility mode is a drop-in replacement to previous packages. RedRibbon holds the promise to accurately extricate detailed information from large comparative analyses.

Funder

The European Union’s Horizon 2020 Research and Innovation Program T2DSystems

The Fonds National de la Recherche Scientifique Fonds National de la Recherche Scientifique

The Foundation Wiener-Anspach

The Funds David and Alice Van Buuren, The Foundation Jaumotte-Demoulin, The Foundation Héger-Masson

The Walloon Region SPW-EER Win2Wal

Welbio-FNRS, Belgium

The Francophone Foundation for Diabetes Research

FWO and FRS-FNRS under the Excellence of Science (EOS) Programme

Innovative Medicines Initiative 2 Joint Undertaking

NIH-HIRN

Innovate2CureType1-Dutch Diabetes Research Foundation

The European Federation of Pharmaceutical Industries and Associations

JDRF

The Leona M. and Harry B. Helmsley Charitable Trust

Publisher

Life Science Alliance, LLC

Subject

Health, Toxicology and Mutagenesis,Plant Science,Biochemistry, Genetics and Molecular Biology (miscellaneous),Ecology

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