title: TTCA: an R package for the identification of differentially expressed genes in time course microarray data.
abstract: BACKGROUND
  The analysis of microarray time series promises a deeper insight into the dynamics of the cellular response following stimulation. A common observation in this type of data is that some genes respond with quick, transient dynamics, while other genes change their expression slowly over time. The existing methods for detecting significant expression dynamics often fail when the expression dynamics show a large heterogeneity. Moreover, these methods often cannot cope with irregular and sparse measurements.
  
  
  RESULTS
  The method proposed here is specifically designed for the analysis of perturbation responses. It combines different scores to capture fast and transient dynamics as well as slow expression changes, and performs well in the presence of low replicate numbers and irregular sampling times. The results are given in the form of tables including links to figures showing the expression dynamics of the respective transcript. These allow to quickly recognise the relevance of detection, to identify possible false positives and to discriminate early and late changes in gene expression. An extension of the method allows the analysis of the expression dynamics of functional groups of genes, providing a quick overview of the cellular response. The performance of this package was tested on microarray data derived from lung cancer cells stimulated with epidermal growth factor (EGF).
  
  
  CONCLUSIONS
  Here we describe a new, efficient method for the analysis of sparse and heterogeneous time course data with high detection sensitivity and transparency. It is implemented as R package TTCA (transcript time course analysis) and can be installed from the Comprehensive R Archive Network, CRAN. The source code is provided with the Additional file 1.
authors.affiliation: Complex Biological Systems Group (BIOMS/IWR), Heidelberg, Im Neuenheimer Feld 294, Heidelberg, 69120, Germany. marco.albrecht@posteo.de.|Systems Biology Group, Université du Luxembourg, 7, avenue du Swing, Belvaux, L-4367, Luxembourg. marco.albrecht@posteo.de.
authors.forename: Marco
authors.initials: M
authors.lastname: Albrecht
authors.affiliation: Complex Biological Systems Group (BIOMS/IWR), Heidelberg, Im Neuenheimer Feld 294, Heidelberg, 69120, Germany.|CCU Neuropathology Group, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 221, Heidelberg, 69120, Germany.
authors.forename: Damian
authors.initials: D
authors.lastname: Stichel
authors.affiliation: Institute of Pathology, Heidelberg University Hospital, Im Neuenheimer Feld 672, Heidelberg, 69120, Germany.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Müller
authors.affiliation: German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg, 69120, Germany.|Translational Lung Research Center (TLRC), Member of the German Center for Lung Research (DZL), Im Neuenheimer Feld 430, Heidelberg, 69120, Germany.
authors.forename: Ruth
authors.initials: R
authors.lastname: Merkle
authors.affiliation: Medical Research Center, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, Mannheim, 68167, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Sticht
authors.affiliation: Medical Research Center, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, Mannheim, 68167, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Gretz
authors.affiliation: German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg, 69120, Germany.|Translational Lung Research Center (TLRC), Member of the German Center for Lung Research (DZL), Im Neuenheimer Feld 430, Heidelberg, 69120, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Klingmüller
authors.affiliation: Institute of Pathology, Heidelberg University Hospital, Im Neuenheimer Feld 672, Heidelberg, 69120, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Breuhahn
authors.affiliation: Complex Biological Systems Group (BIOMS/IWR), Heidelberg, Im Neuenheimer Feld 294, Heidelberg, 69120, Germany.|Frankfurt Institute for Advanced Studies (FIAS), Goethe University Frankfurt, Ruth-Moufang-Straße 1, Frankfurt am Main, 60438, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Matthäus
mesh_terms: D019295:Computational Biology / Q000379:methods*; D015870:Gene Expression; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*
keywords: Differential expression; EGF; Gene ontology; Gene set analysis; Stimulation experiments; Time series