title: A hierarchical Bayesian model for flexible module discovery in three-way time-series data.
abstract: BACKGROUND
  Detecting modules of co-ordinated activity is fundamental in the analysis of large biological studies. For two-dimensional data (e.g. genes × patients), this is often done via clustering or biclustering. More recently, studies monitoring patients over time have added another dimension. Analysis is much more challenging in this case, especially when time measurements are not synchronized. New methods that can analyze three-way data are thus needed.
  
  
  RESULTS
  We present a new algorithm for finding coherent and flexible modules in three-way data. Our method can identify both core modules that appear in multiple patients and patient-specific augmentations of these core modules that contain additional genes. Our algorithm is based on a hierarchical Bayesian data model and Gibbs sampling. The algorithm outperforms extant methods on simulated and on real data. The method successfully dissected key components of septic shock response from time series measurements of gene expression. Detected patient-specific module augmentations were informative for disease outcome. In analyzing brain functional magnetic resonance imaging time series of subjects at rest, it detected the pertinent brain regions involved.
  
  
  METHODS
  R code and data are available at http://acgt.cs.tau.ac.il/twigs/.
authors.affiliation: The Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv 69978, Israel, Department of Statistics and OR, School of Mathematical Sciences, Tel Aviv University, Tel Aviv 69978, Israel, Functional Brain Center, Wohl Institute for Advanced Imaging, Tel Aviv Sourasky Medical Center, Tel Aviv 64239, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: David
authors.initials: D
authors.lastname: Amar
authors.affiliation: The Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv 69978, Israel, Department of Statistics and OR, School of Mathematical Sciences, Tel Aviv University, Tel Aviv 69978, Israel, Functional Brain Center, Wohl Institute for Advanced Imaging, Tel Aviv Sourasky Medical Center, Tel Aviv 64239, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Daniel
authors.initials: D
authors.lastname: Yekutieli
authors.affiliation: The Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv 69978, Israel, Department of Statistics and OR, School of Mathematical Sciences, Tel Aviv University, Tel Aviv 69978, Israel, Functional Brain Center, Wohl Institute for Advanced Imaging, Tel Aviv Sourasky Medical Center, Tel Aviv 64239, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel The Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv 69978, Israel, Department of Statistics and OR, School of Mathematical Sciences, Tel Aviv University, Tel Aviv 69978, Israel, Functional Brain Center, Wohl Institute for Advanced Imaging, Tel Aviv Sourasky Medical Center, Tel Aviv 64239, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel The Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv 69978, Israel, Department of Statistics and OR, School of Mathematical Sciences, Tel Aviv University, Tel Aviv 69978, Israel, Functional Brain Center, Wohl Institute for Advanced Imaging, Tel Aviv Sourasky Medical Center, Tel Aviv 64239, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Adi
authors.initials: A
authors.lastname: Maron-Katz
authors.affiliation: The Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv 69978, Israel, Department of Statistics and OR, School of Mathematical Sciences, Tel Aviv University, Tel Aviv 69978, Israel, Functional Brain Center, Wohl Institute for Advanced Imaging, Tel Aviv Sourasky Medical Center, Tel Aviv 64239, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel The Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv 69978, Israel, Department of Statistics and OR, School of Mathematical Sciences, Tel Aviv University, Tel Aviv 69978, Israel, Functional Brain Center, Wohl Institute for Advanced Imaging, Tel Aviv Sourasky Medical Center, Tel Aviv 64239, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Talma
authors.initials: T
authors.lastname: Hendler
authors.affiliation: The Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv 69978, Israel, Department of Statistics and OR, School of Mathematical Sciences, Tel Aviv University, Tel Aviv 69978, Israel, Functional Brain Center, Wohl Institute for Advanced Imaging, Tel Aviv Sourasky Medical Center, Tel Aviv 64239, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Ron
authors.initials: R
authors.lastname: Shamir
mesh_terms: D000465:Algorithms; D001499:Bayes Theorem; D001931:Brain Mapping / Q000379:methods*; D016000:Cluster Analysis; D038524:Diffusion Magnetic Resonance Imaging; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D012772:Shock, Septic / Q000235:genetics*; D013997:Time Factors