title: Pattern recognition methods to relate time profiles of gene expression with phenotypic data: a comparative study.
abstract: BACKGROUND
  Comparing time courses of gene expression with time courses of phenotypic data may provide new insights in cellular mechanisms. In this study, we compared the performance of five pattern recognition methods with respect to their ability to relate genes and phenotypic data: one classical method (k-means) and four methods especially developed for time series [Short Time-series Expression Miner (STEM), Linear Mixed Model mixtures, Dynamic Time Warping for -Omics and linear modeling with R/Bioconductor limma package]. The methods were evaluated using data available from toxicological studies that had the aim to relate gene expression with phenotypic endpoints (i.e. to develop biomarkers for adverse outcomes). Additionally, technical aspects (influence of noise, number of time points and number of replicates) were evaluated on simulated data.
  
  
  RESULTS
  None of the methods outperforms the others in terms of biology. Linear modeling with limma is mostly influenced by noise. STEM is mostly influenced by the number of biological replicates in the dataset, whereas k-means and linear modeling with limma are mostly influenced by the number of time points. In most cases, the results of the methods complement each other. We therefore provide recommendations to integrate the five methods.
  
  
  BACKGROUND
  The Matlab code for the simulations performed in this research is available in the Supplementary Data (Word file). The microarray data analysed in this paper are available at ArrayExpress (E-TOXM-22 and E-TOXM-23) and Gene Expression Omnibus (GSE39291). The phenotypic data are available in the Supplementary Data (Excel file). Links to the pattern recognition tools compared in this paper are provided in the main text.
  
  
  BACKGROUND
  d.hendrickx@maastrichtuniversity.nl
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors.affiliation: Department of Toxicogenomics, School of Oncology and Developmental Biology (GROW), Maastricht University, 6200 MD Maastricht, The Netherlands.
authors.forename: Diana M
authors.initials: DM
authors.lastname: Hendrickx
authors.affiliation: Department of Toxicogenomics, School of Oncology and Developmental Biology (GROW), Maastricht University, 6200 MD Maastricht, The Netherlands.
authors.forename: Danyel G J
authors.initials: DG
authors.lastname: Jennen
authors.affiliation: Department of Toxicogenomics, School of Oncology and Developmental Biology (GROW), Maastricht University, 6200 MD Maastricht, The Netherlands.
authors.forename: Jacob J
authors.initials: JJ
authors.lastname: Briedé
authors.affiliation: Department of Toxicogenomics, School of Oncology and Developmental Biology (GROW), Maastricht University, 6200 MD Maastricht, The Netherlands.
authors.forename: Rachel
authors.initials: R
authors.lastname: Cavill
authors.affiliation: Department of Toxicogenomics, School of Oncology and Developmental Biology (GROW), Maastricht University, 6200 MD Maastricht, The Netherlands.
authors.forename: Theo M
authors.initials: TM
authors.lastname: de Kok
authors.affiliation: Department of Toxicogenomics, School of Oncology and Developmental Biology (GROW), Maastricht University, 6200 MD Maastricht, The Netherlands.
authors.forename: Jos C S
authors.initials: JC
authors.lastname: Kleinjans
mesh_terms: D000933:Antifibrinolytic Agents / Q000494:pharmacology; D001564:Benzo(a)pyrene / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000235:genetics; D003198:Computer Simulation; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D016014:Linear Models; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010363:Pattern Recognition, Automated / Q000379:methods*; D010641:Phenotype; D012984:Software; D013997:Time Factors; D024483:Vitamin K 3 / Q000494:pharmacology
chemical_list: D000933:Antifibrinolytic Agents; D001564:Benzo(a)pyrene; D024483:Vitamin K 3