title: Combining optimization and machine learning techniques for genome-wide prediction of human cell cycle-regulated genes.
abstract: BACKGROUND
  The identification of cell cycle-regulated genes through the cyclicity of messenger RNAs in genome-wide studies is a difficult task due to the presence of internal and external noise in microarray data. Moreover, the analysis is also complicated by the loss of synchrony occurring in cell cycle experiments, which often results in additional background noise.
  
  
  RESULTS
  To overcome these problems, here we propose the LEON (LEarning and OptimizatioN) algorithm, able to characterize the 'cyclicity degree' of a gene expression time profile using a two-step cascade procedure. The first step identifies a potentially cyclic behavior by means of a Support Vector Machine trained with a reliable set of positive and negative examples. The second step selects those genes having peak timing consistency along two cell cycles by means of a non-linear optimization technique using radial basis functions. To prove the effectiveness of our combined approach, we use recently published human fibroblasts cell cycle data and, performing in vivo experiments, we demonstrate that our computational strategy is able not only to confirm well-known cell cycle-regulated genes, but also to predict not yet identified ones.
  
  
  METHODS
  All scripts for implementation can be obtained on request.
authors.affiliation: Dipartimento di Ingegneria Informatica, Automatica e Gestionale, Sapienza Università di Roma, Rome, Italy and Istituto Nazionale dei Tumori Regina Elena, Dipartimento di Oncologia Sperimentale, Laboratorio di Oncogenesi Molecolare, Rome, Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: De Santis
authors.forename: Francesco
authors.initials: F
authors.lastname: Rinaldi
authors.forename: Emmanuela
authors.initials: E
authors.lastname: Falcone
authors.forename: Stefano
authors.initials: S
authors.lastname: Lucidi
authors.forename: Giulia
authors.initials: G
authors.lastname: Piaggio
authors.forename: Aymone
authors.initials: A
authors.lastname: Gurtner
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Farina
mesh_terms: D000465:Algorithms; D001185:Artificial Intelligence; D002453:Cell Cycle / Q000235:genetics*; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D018816:Genes, cdc / Q000235:genetics*; D015894:Genome, Human; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D060388:Support Vector Machine
chemical_list: D012333:RNA, Messenger