title: ChlamyNET: a Chlamydomonas gene co-expression network reveals global properties of the transcriptome and the early setup of key co-expression patterns in the green lineage.
abstract: BACKGROUND
  Chlamydomonas reinhardtii is the model organism that serves as a reference for studies in algal genomics and physiology. It is of special interest in the study of the evolution of regulatory pathways from algae to higher plants. Additionally, it has recently gained attention as a potential source for bio-fuel and bio-hydrogen production. The genome of Chlamydomonas is available, facilitating the analysis of its transcriptome by RNA-seq data. This has produced a massive amount of data that remains fragmented making necessary the application of integrative approaches based on molecular systems biology.
  
  
  RESULTS
  We constructed a gene co-expression network based on RNA-seq data and developed a web-based tool, ChlamyNET, for the exploration of the Chlamydomonas transcriptome. ChlamyNET exhibits a scale-free and small world topology. Applying clustering techniques, we identified nine gene clusters that capture the structure of the transcriptome under the analyzed conditions. One of the most central clusters was shown to be involved in carbon/nitrogen metabolism and signalling, whereas one of the most peripheral clusters was involved in DNA replication and cell cycle regulation. The transcription factors and regulators in the Chlamydomonas genome have been identified in ChlamyNET. The biological processes potentially regulated by them as well as their putative transcription factor binding sites were determined. The putative light regulated transcription factors and regulators in the Chlamydomonas genome were analyzed in order to provide a case study on the use of ChlamyNET. Finally, we used an independent data set to cross-validate the predictive power of ChlamyNET.
  
  
  CONCLUSIONS
  The topological properties of ChlamyNET suggest that the Chlamydomonas transcriptome posseses important characteristics related to error tolerance, vulnerability and information propagation. The central part of ChlamyNET constitutes the core of the transcriptome where most authoritative hub genes are located interconnecting key biological processes such as light response with carbon and nitrogen metabolism. Our study reveals that key elements in the regulation of carbon and nitrogen metabolism, light response and cell cycle identified in higher plants were already established in Chlamydomonas. These conserved elements are not only limited to transcription factors, regulators and their targets, but also include the cis-regulatory elements recognized by them.
authors.affiliation: Departamento de Ciencias de la Computación e Inteligencia Artificial, Universidad de Sevilla, Reina Mercedes s/n, 41012, Sevilla, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Romero-Campero
authors.affiliation: Departamento de Ciencias de la Computación e Inteligencia Artificial, Universidad de Sevilla, Reina Mercedes s/n, 41012, Sevilla, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Perez-Hurtado
authors.affiliation: Instituto de Bioquímica Vegetal y Fotosíntesis, Universidad de Sevilla-CSIC, Americo Vespucio 49, 41092, Sevilla, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Lucas-Reina
authors.affiliation: Instituto de Bioquímica Vegetal y Fotosíntesis, Universidad de Sevilla-CSIC, Americo Vespucio 49, 41092, Sevilla, Spain.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Romero
authors.affiliation: Instituto de Bioquímica Vegetal y Fotosíntesis, Universidad de Sevilla-CSIC, Americo Vespucio 49, 41092, Sevilla, Spain. federico.valverde@ibvf.csic.es.
authors.forename: Federico
authors.identifier: http://orcid.org/0000-0001-8063-0974
authors.initials: F
authors.lastname: Valverde
mesh_terms: D016825:Chlamydomonas reinhardtii / Q000235:genetics*; D016000:Cluster Analysis; D048028:DNA, Algal / Q000235:genetics; D053263:Gene Regulatory Networks; D005810:Multigene Family; D012045:Regulatory Sequences, Nucleic Acid; D017423:Sequence Analysis, RNA; D012984:Software; D014157:Transcription Factors / Q000235:genetics; D059467:Transcriptome
chemical_list: D048028:DNA, Algal; D014157:Transcription Factors
keywords: Chlamydomonas reinhardtii; RNA-seq; gene co-expression networks; green algae; light-regulated transcription factors and transcriptional regulators; molecular systems biology; transcriptomics