title: Analysis of the dynamic co-expression network of heart regeneration in the zebrafish.
abstract: The zebrafish has the capacity to regenerate its heart after severe injury. While the function of a few genes during this process has been studied, we are far from fully understanding how genes interact to coordinate heart regeneration. To enable systematic insights into this phenomenon, we generated and integrated a dynamic co-expression network of heart regeneration in the zebrafish and linked systems-level properties to the underlying molecular events. Across multiple post-injury time points, the network displays topological attributes of biological relevance. We show that regeneration steps are mediated by modules of transcriptionally coordinated genes, and by genes acting as network hubs. We also established direct associations between hubs and validated drivers of heart regeneration with murine and human orthologs. The resulting models and interactive analysis tools are available at http://infused.vital-it.ch. Using a worked example, we demonstrate the usefulness of this unique open resource for hypothesis generation and in silico screening for genes involved in heart regeneration.
authors.affiliation: NorLux Neuro-Oncology Laboratory, Oncology Department, Luxembourg Institute of Health (LIH), Luxembourg, L-1526, Luxembourg.
authors.forename: Sophie
authors.initials: S
authors.lastname: Rodius
authors.affiliation: NorLux Neuro-Oncology Laboratory, Oncology Department, Luxembourg Institute of Health (LIH), Luxembourg, L-1526, Luxembourg.
authors.forename: Anna
authors.initials: A
authors.lastname: Fournier
authors.affiliation: Vital-IT Systems Biology Division, SIB Swiss Institute of Bioinformatics, Lausanne, CH-1015, Switzerland.
authors.forename: Lou
authors.initials: L
authors.lastname: Götz
authors.affiliation: Vital-IT Systems Biology Division, SIB Swiss Institute of Bioinformatics, Lausanne, CH-1015, Switzerland.
authors.forename: Robin
authors.initials: R
authors.lastname: Liechti
authors.affiliation: Vital-IT Systems Biology Division, SIB Swiss Institute of Bioinformatics, Lausanne, CH-1015, Switzerland.
authors.forename: Isaac
authors.initials: I
authors.lastname: Crespo
authors.affiliation: NorLux Neuro-Oncology Laboratory, Oncology Department, Luxembourg Institute of Health (LIH), Luxembourg, L-1526, Luxembourg.
authors.forename: Susanne
authors.initials: S
authors.lastname: Merz
authors.affiliation: Genomics Research Unit, Oncology Department, LIH, Luxembourg, L-1526, Luxembourg.
authors.forename: Petr V
authors.initials: PV
authors.lastname: Nazarov
authors.affiliation: NorLux Neuro-Oncology Laboratory, Oncology Department, Luxembourg Institute of Health (LIH), Luxembourg, L-1526, Luxembourg.|Vrije Universiteit Amsterdam, Amsterdam, 1081 HV, The Netherlands.
authors.forename: Niek
authors.initials: N
authors.lastname: de Klein
authors.affiliation: NorLux Neuro-Oncology Laboratory, Oncology Department, Luxembourg Institute of Health (LIH), Luxembourg, L-1526, Luxembourg.
authors.forename: Céline
authors.initials: C
authors.lastname: Jeanty
authors.affiliation: Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Juan M
authors.initials: JM
authors.lastname: González-Rosa
authors.affiliation: Genomics Research Unit, Oncology Department, LIH, Luxembourg, L-1526, Luxembourg.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Muller
authors.affiliation: Genomics Research Unit, Oncology Department, LIH, Luxembourg, L-1526, Luxembourg.
authors.forename: Francois
authors.initials: F
authors.lastname: Bernardin
authors.affiliation: NorLux Neuro-Oncology Laboratory, Oncology Department, Luxembourg Institute of Health (LIH), Luxembourg, L-1526, Luxembourg.
authors.forename: Simone P
authors.initials: SP
authors.lastname: Niclou
authors.affiliation: Genomics Research Unit, Oncology Department, LIH, Luxembourg, L-1526, Luxembourg.
authors.forename: Laurent
authors.initials: L
authors.lastname: Vallar
authors.affiliation: Epicardium Development and Regeneration group, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC-ISCIII), Madrid, 28029, Spain.
authors.forename: Nadia
authors.initials: N
authors.lastname: Mercader
authors.affiliation: Vital-IT Systems Biology Division, SIB Swiss Institute of Bioinformatics, Lausanne, CH-1015, Switzerland.
authors.forename: Mark
authors.initials: M
authors.lastname: Ibberson
authors.affiliation: Vital-IT Systems Biology Division, SIB Swiss Institute of Bioinformatics, Lausanne, CH-1015, Switzerland.|Center for Integrative Genomics, University of Lausanne, Lausanne, CH-1015, Switzerland.|Department of Biochemistry, University of Geneva, 1211 Geneva 4, Switzerland.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Xenarios
authors.affiliation: NorLux Neuro-Oncology Laboratory, Oncology Department, Luxembourg Institute of Health (LIH), Luxembourg, L-1526, Luxembourg.
authors.forename: Francisco
authors.initials: F
authors.lastname: Azuaje
mesh_terms: D000818:Animals; D015870:Gene Expression; D006321:Heart / Q000502:physiology*; D006335:Heart Injuries / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D012038:Regeneration; D059467:Transcriptome; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics
chemical_list: D029961:Zebrafish Proteins