title: Methods for time series analysis of RNA-seq data with application to human Th17 cell differentiation.
abstract: BACKGROUND
  Gene expression profiling using RNA-seq is a powerful technique for screening RNA species' landscapes and their dynamics in an unbiased way. While several advanced methods exist for differential expression analysis of RNA-seq data, proper tools to anal.yze RNA-seq time-course have not been proposed.
  
  
  RESULTS
  In this study, we use RNA-seq to measure gene expression during the early human T helper 17 (Th17) cell differentiation and T-: cell activation (Th0). To quantify Th17-: specific gene expression dynamics, we present a novel statistical methodology, DyNB, for analyzing time-course RNA-seq data. We use non-parametric Gaussian processes to model temporal correlation in gene expression and combine that with negative binomial likelihood for the count data. To account for experiment-: specific biases in gene expression dynamics, such as differences in cell differentiation efficiencies, we propose a method to rescale the dynamics between replicated measurements. We develop an MCMC sampling method to make inference of differential expression dynamics between conditions. DyNB identifies several known and novel genes involved in Th17 differentiation. Analysis of differentiation efficiencies revealed consistent patterns in gene expression dynamics between different cultures. We use qRT-PCR to validate differential expression and differentiation efficiencies for selected genes. Comparison of the results with those obtained via traditional timepoint-: wise analysis shows that time-course analysis together with time rescaling between cultures identifies differentially expressed genes which would not otherwise be detected.
  
  
  BACKGROUND
  An implementation of the proposed computational methods will be available at http://research.ics.aalto.fi/csb/software/
authors.affiliation: Department of Information and Computer Science, Aalto University, FI-00076 Aalto, Finland, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA and Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, FI-20520 Turku, Finland.
authors.forename: Tarmo
authors.initials: T
authors.lastname: Äijö
authors.affiliation: Department of Information and Computer Science, Aalto University, FI-00076 Aalto, Finland, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA and Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, FI-20520 Turku, Finland.
authors.forename: Vincent
authors.initials: V
authors.lastname: Butty
authors.affiliation: Department of Information and Computer Science, Aalto University, FI-00076 Aalto, Finland, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA and Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, FI-20520 Turku, Finland.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Information and Computer Science, Aalto University, FI-00076 Aalto, Finland, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA and Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, FI-20520 Turku, Finland.
authors.forename: Verna
authors.initials: V
authors.lastname: Salo
authors.affiliation: Department of Information and Computer Science, Aalto University, FI-00076 Aalto, Finland, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA and Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, FI-20520 Turku, Finland.
authors.forename: Subhash
authors.initials: S
authors.lastname: Tripathi
authors.affiliation: Department of Information and Computer Science, Aalto University, FI-00076 Aalto, Finland, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA and Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, FI-20520 Turku, Finland.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Burge
authors.affiliation: Department of Information and Computer Science, Aalto University, FI-00076 Aalto, Finland, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA and Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, FI-20520 Turku, Finland.
authors.forename: Riitta
authors.initials: R
authors.lastname: Lahesmaa
authors.affiliation: Department of Information and Computer Science, Aalto University, FI-00076 Aalto, Finland, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA and Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, FI-20520 Turku, FinlandDepartment of Information and Computer Science, Aalto University, FI-00076 Aalto, Finland, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA and Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, FI-20520 Turku, Finland.
authors.forename: Harri
authors.initials: H
authors.lastname: Lähdesmäki
mesh_terms: D002454:Cell Differentiation / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D007231:Infant, Newborn; D016011:Normal Distribution; D017423:Sequence Analysis, RNA / Q000379:methods*; D058504:Th17 Cells / Q000166:cytology / Q000378:metabolism*