title: Arabidopsis ensemble reverse-engineered gene regulatory network discloses interconnected transcription factors in oxidative stress.
abstract: The abiotic stress response in plants is complex and tightly controlled by gene regulation. We present an abiotic stress gene regulatory network of 200,014 interactions for 11,938 target genes by integrating four complementary reverse-engineering solutions through average rank aggregation on an Arabidopsis thaliana microarray expression compendium. This ensemble performed the most robustly in benchmarking and greatly expands upon the availability of interactions currently reported. Besides recovering 1182 known regulatory interactions, cis-regulatory motifs and coherent functionalities of target genes corresponded with the predicted transcription factors. We provide a valuable resource of 572 abiotic stress modules of coregulated genes with functional and regulatory information, from which we deduced functional relationships for 1966 uncharacterized genes and many regulators. Using gain- and loss-of-function mutants of seven transcription factors grown under control and salt stress conditions, we experimentally validated 141 out of 271 predictions (52% precision) for 102 selected genes and mapped 148 additional transcription factor-gene regulatory interactions (49% recall). We identified an intricate core oxidative stress regulatory network where NAC13, NAC053, ERF6, WRKY6, and NAC032 transcription factors interconnect and function in detoxification. Our work shows that ensemble reverse-engineering can generate robust biological hypotheses of gene regulation in a multicellular eukaryote that can be tested by medium-throughput experimental validation.
authors.affiliation: Department of Plant Systems Biology, VIB, 9052 Gent, Belgium Department of Plant Biotechnology and Bioinformatics, Ghent University, 9052 Gent, Belgium vanessa.vermeirssen@psb.vib-ugent.be.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Vermeirssen
authors.affiliation: Department of Plant Systems Biology, VIB, 9052 Gent, Belgium Department of Plant Biotechnology and Bioinformatics, Ghent University, 9052 Gent, Belgium.
authors.forename: Inge
authors.initials: I
authors.lastname: De Clercq
authors.affiliation: Department of Plant Systems Biology, VIB, 9052 Gent, Belgium Department of Plant Biotechnology and Bioinformatics, Ghent University, 9052 Gent, Belgium.
authors.forename: Thomas
authors.initials: T
authors.lastname: Van Parys
authors.affiliation: Department of Plant Systems Biology, VIB, 9052 Gent, Belgium Department of Plant Biotechnology and Bioinformatics, Ghent University, 9052 Gent, Belgium.
authors.forename: Frank
authors.initials: F
authors.lastname: Van Breusegem
authors.affiliation: Department of Plant Systems Biology, VIB, 9052 Gent, Belgium Department of Plant Biotechnology and Bioinformatics, Ghent University, 9052 Gent, Belgium Genomics Research Institute, University of Pretoria, Pretoria 0028, South Africa.
authors.forename: Yves
authors.initials: Y
authors.lastname: Van de Peer
mesh_terms: D000465:Algorithms; D017360:Arabidopsis / Q000235:genetics* / Q000502:physiology; D002874:Chromosome Mapping; D053263:Gene Regulatory Networks; D018384:Oxidative Stress / Q000235:genetics*; D059386:Reverse Genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D014157:Transcription Factors