FunCoup v6: advancing functional networks across species with directed links and improved user experience

Authors

Affiliations

Davide Buzzao

Science for Life Laboratory, Department of Gene Technology, KTH Royal Institute of Technology, Stockholm, Sweden

Yuvarani Masarapu

Science for Life Laboratory, Department of Gene Technology, KTH Royal Institute of Technology, Stockholm, Sweden

Egle Cekanaviciute

Space Biosciences Division, NASA Ames Research Center, CA, USA

Zaneta Andrusivova

Science for Life Laboratory, Department of Gene Technology, KTH Royal Institute of Technology, Stockholm, Sweden

Jakub O. Westholm

National Bioinformatics Infrastructure Sweden, Department of Biochemistry and Biophysics, Stockholm University, Science for Life, Sweden

Åsa Björklund

Department of Cell and Molecular Biology, National Bioinformatics Infrastructure Sweden, Uppsala University, Sweden

Robin Fallegger

Heidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, Bioquan, DE

Pau Badia-i-Mompel

Heidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, Bioquan, DE

Valery Boyko

Space Biosciences Division, NASA Ames Research Center, CA, USA

Bionetics, Yorktown, VA, USA

Shubha Vasisht

Department of Biomedical and Health Informatics, The Children’s Hospital of Philadelphia Research Institute, Philadelphia, US

Amanda Saravia-Butler

KBR, Space Biosciences Division, NASA Ames Research Center, Moffett Field, CA, USA

Samrawit Gebre

Space Biosciences Division, NASA Ames Research Center, CA, USA

Enikö Lázár

Science for Life Laboratory, Department of Gene Technology, KTH Royal Institute of Technology, Stockholm, Sweden

Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden

Marta Graziano

Department of Neuroscience, Karolinska Institutet, Biomedicum, Solna, Sweden

Solene Frapard

Science for Life Laboratory, Department of Gene Technology, KTH Royal Institute of Technology, Stockholm, Sweden

Robert G. Hinshaw

NASA Postdoctoral Program - Oak Ridge Associated Universities, NASA Ames Research Center, CA, USA

Olaf Bergmann

Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden

Deanne M Taylor

Department of Biomedical and Health Informatics, The Children’s Hospital of Philadelphia Research Institute, Philadelphia, US

Department of Pediatrics, The University of Pennsylvania Perelman School of Medicine, Philadelphia, USA

Douglas C. Wallace

Department of Pediatrics, The University of Pennsylvania Perelman School of Medicine, Philadelphia, USA

Christer Sylven

Department of Medicine, Karolinska Institute, Huddinge, Sweden

Konstantinos Meletis

Department of Neuroscience, Karolinska Institutet, Biomedicum, Solna, Sweden

Julio Saez-Rodriguez

Heidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, Bioquan, DE

Jonathan M. Galazka

Space Biosciences Division, NASA Ames Research Center, CA, USA

Sylvain V. Costes

Space Biosciences Division, NASA Ames Research Center, CA, USA

Stefania Giacomello

Science for Life Laboratory, Department of Gene Technology, KTH Royal Institute of Technology, Stockholm, Sweden

Abstract

FunCoup v6 (https://funcoup.org/) represents a significant advancement in global functional association networks, aiming to provide researchers with a comprehensive view of the functional coupling interactome. This update introduces novel methodologies and integrated tools for improved network inference and analysis. Major new developments in FunCoup v6 include vastly expanding the coverage of gene regulatory links, a new framework for bin-free Bayesian training, and a new website. A substantial increase in regulatory links was obtained for 13 species, with around half a million directed links between 838 transcription factors and 14,989 target genes only within the human network, enhancing our understanding of transcriptional regulation. In addition to MaxLink, FunCoup v6 integrates a new tool for disease and drug target module identification using the TOPAS algorithm. To expand the utility of the resource for biomedical research, it incorporates KEGG pathway enrichment analysis using the ANUBIX, BinoX, and EASE algorithms. The unique comparative interactomics analysis in FunCoup provides insights of network conservation, now allowing users to align orthologs only or query each species network independently. Bin-free training was applied to 22 primary species in FunCoup v6, and in addition networks were generated for all remaining 618 species in InParanoidDB 9 via a new ortholog-based method to transfer entire networks from the closest primary species. Accompanying these advancements, FunCoup v6 features a new redesigned website, together with updated API functionalities, providing users with enhanced accessibility and usability. FunCoup v6 demonstrates superior benchmark performance compared to other large functional association networks.