title: Discovering time-lagged rules from microarray data using gene profile classifiers.
abstract: BACKGROUND
  Gene regulatory networks have an essential role in every process of life. In this regard, the amount of genome-wide time series data is becoming increasingly available, providing the opportunity to discover the time-delayed gene regulatory networks that govern the majority of these molecular processes.
  
  
  RESULTS
  This paper aims at reconstructing gene regulatory networks from multiple genome-wide microarray time series datasets. In this sense, a new model-free algorithm called GRNCOP2 (Gene Regulatory Network inference by Combinatorial OPtimization 2), which is a significant evolution of the GRNCOP algorithm, was developed using combinatorial optimization of gene profile classifiers. The method is capable of inferring potential time-delay relationships with any span of time between genes from various time series datasets given as input. The proposed algorithm was applied to time series data composed of twenty yeast genes that are highly relevant for the cell-cycle study, and the results were compared against several related approaches. The outcomes have shown that GRNCOP2 outperforms the contrasted methods in terms of the proposed metrics, and that the results are consistent with previous biological knowledge. Additionally, a genome-wide study on multiple publicly available time series data was performed. In this case, the experimentation has exhibited the soundness and scalability of the new method which inferred highly-related statistically-significant gene associations.
  
  
  CONCLUSIONS
  A novel method for inferring time-delayed gene regulatory networks from genome-wide time series datasets is proposed in this paper. The method was carefully validated with several publicly available data sets. The results have demonstrated that the algorithm constitutes a usable model-free approach capable of predicting meaningful relationships between genes, revealing the time-trends of gene regulation.
authors.affiliation: Laboratorio de Investigación y Desarrollo en Computación Científica (LIDeCC), Departamento de Ciencias e Ingeniería de la Computación, Universidad Nacional del Sur, Av, Alem 1253, 8000, Bahía Blanca, Argentina.
authors.forename: Cristian A
authors.initials: CA
authors.lastname: Gallo
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Carballido
authors.forename: Ignacio
authors.initials: I
authors.lastname: Ponzoni
mesh_terms: D000465:Algorithms; D030541:Databases, Genetic; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics
chemical_list: D029701:Saccharomyces cerevisiae Proteins