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Albrecht M, Stichel D, Müller B, et al. TTCA: an R package for the identification of differentially expressed genes in time course microarray data. BMC Bioinformatics. 2017;18(1):33doi: 10.1186/s12859-016-1440-8.
Albrecht, M., Stichel, D., Müller, B., Merkle, R., Sticht, C., Gretz, N., Klingmüller, U., Breuhahn, K., & Matthäus, F. (2017). TTCA: an R package for the identification of differentially expressed genes in time course microarray data. BMC bioinformatics, 18(1), 33. https://doi.org/10.1186/s12859-016-1440-8
Albrecht, Marco, et al. "TTCA: an R package for the identification of differentially expressed genes in time course microarray data." BMC bioinformatics vol. 18,1 (2017): 33. doi: https://doi.org/10.1186/s12859-016-1440-8
Albrecht M, Stichel D, Müller B, Merkle R, Sticht C, Gretz N, Klingmüller U, Breuhahn K, Matthäus F. TTCA: an R package for the identification of differentially expressed genes in time course microarray data. BMC Bioinformatics. 2017 Jan 14;18(1):33. doi: 10.1186/s12859-016-1440-8. PMID: 28088176; PMCID: PMC5237546.
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BMC Bioinformatics. 2017 Jan 14;18(1):33. doi: 10.1186/s12859-016-1440-8.

TTCA: an R package for the identification of differentially expressed genes in time course microarray data.

BMC bioinformatics

Marco Albrecht, Damian Stichel, Benedikt Müller, Ruth Merkle, Carsten Sticht, Norbert Gretz, Ursula Klingmüller, Kai Breuhahn, Franziska Matthäus

Affiliations

  1. Complex Biological Systems Group (BIOMS/IWR), Heidelberg, Im Neuenheimer Feld 294, Heidelberg, 69120, Germany. [email protected].
  2. Systems Biology Group, Université du Luxembourg, 7, avenue du Swing, Belvaux, L-4367, Luxembourg. [email protected].
  3. Complex Biological Systems Group (BIOMS/IWR), Heidelberg, Im Neuenheimer Feld 294, Heidelberg, 69120, Germany.
  4. CCU Neuropathology Group, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 221, Heidelberg, 69120, Germany.
  5. Institute of Pathology, Heidelberg University Hospital, Im Neuenheimer Feld 672, Heidelberg, 69120, Germany.
  6. German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg, 69120, Germany.
  7. Translational Lung Research Center (TLRC), Member of the German Center for Lung Research (DZL), Im Neuenheimer Feld 430, Heidelberg, 69120, Germany.
  8. Medical Research Center, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, Mannheim, 68167, Germany.
  9. Frankfurt Institute for Advanced Studies (FIAS), Goethe University Frankfurt, Ruth-Moufang-Straße 1, Frankfurt am Main, 60438, Germany.

PMID: 28088176 PMCID: PMC5237546 DOI: 10.1186/s12859-016-1440-8

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).

CONCLUSION: 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.

Keywords: Differential expression; EGF; Gene ontology; Gene set analysis; Stimulation experiments; Time series

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