title: Analysis of changes in transcription start site distribution by a classification approach.
abstract: Change in transcription start site (TSS) usage is an important mechanism for the control of transcription process, and has a significant effect on the isoforms being transcribed. One of the goals in the study of TSS is the understanding of how and why their usage differs in different tissues or under different conditions. In light of recent efforts in the mapping of transcription start site landscape using high-throughput sequencing approaches, a quantitative and automated method is needed to process all the data that are being produced. In this work we propose a statistical approach that will classify changes in TSS distribution between different samples into several categories of changes that may have biological significance. Genes selected by the classifiers can then be analyzed together with additional supporting data to determine their biological significance. We use a set of time-course TSS data from mouse dendritic cells stimulated with lipopolysaccharide (LPS) to demonstrate the usefulness of our method.
authors.affiliation: Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Kuo-ching
authors.initials: KC
authors.lastname: Liang
authors.affiliation: Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa-shi, Chiba-ken 227-8561, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Laboratory of Host Defense, World Premier International Immunology Frontier Research Center, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Yutaro
authors.initials: Y
authors.lastname: Kumagai
authors.affiliation: Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan; Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa-shi, Chiba-ken 227-8561, Japan. Electronic address: knakai@ims.u-tokyo.ac.jp.
authors.forename: Kenta
authors.initials: K
authors.lastname: Nakai
mesh_terms: D000818:Animals; D003627:Data Interpretation, Statistical; D030541:Databases, Genetic; D003713:Dendritic Cells / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation; D063990:Gene Ontology; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D011401:Promoter Regions, Genetic; D000090063:Proto-Oncogene Mas; D015398:Signal Transduction / Q000235:genetics; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism*; D024363:Transcription Initiation Site
chemical_list: D008070:Lipopolysaccharides; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D051193:Toll-Like Receptors
keywords: AP-1; Alternative promoters; BAI3; CADM2; CAGE; ChIP; Changes of TSS distribution; DNA complementary to RNA; FGF14; GADD45g; GM-CSF; Granulocyte macrophage colony-stimulating factor; IFIT1; IFNR; IKAROS family zinc finger 1; IKK; IKZF1; IL27; IL6; IRAK; IRF; IRG1; ISG15; Interferon regulator factor; JAK/STAT; Janus kinase/signal transducers and activators of transcription; K(v); K(v) channel interacting protein 4; KCNIP4; LPS; LRRTM4; LSAMP; MAPK; Mouse dendritic cells; MyD88; NF-κB; NFKBIZ; NRG3; NRXN1; PCDH9; RIP1; SOCS1; STAT5a; Statistical approach; TAK1; TANK; TANK-binding kinase 1; TBK1; TGF-beta-activated kinase 1; TLR4; TNF receptor associated factors; TNF-α; TRAF; TRAF family member-associated NF-κB activator; TRAF-type zinc finger domain containing 1; TRAFD1; TRIF; TS; TSC; TSS; TTR; Time-course TSS data; Tumor necrosis factor alpha; USP18; brain-specific angiogenesis inhibitor 3; cDNA; cap analysis of gene expression; cell adhesion molecule 2; chromatin immunoprecipitation; fibroblast growth factor 14; growth arrest and DNA-damage-inducible 45 gamma; immunoresponsive gene 1; inhibitor of kappa B kinase; interferon production regulator; interferon-induced protein with tetratricopeptide repeats 1; interleukin 27; interleukin 6; interleukin receptor-associated kinase; jun proto-oncogene; leucine rich repeat transmembrane neuronal 4; limbic system-associated membrane protein; lipopolysaccharide; mitogen-activated protein kinase; myeloid differentiation primary response gene 88; neuregulin 3; neurexin 1; nuclear factor kappa B; nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, zeta; protocadherin 9; receptor (TNFRSF)-interacting serine-threonine kinase 1; signal transducer and activator of transcription 5A; suppressor of cytokine signaling 1; tissue specificity score; toll-like receptor 4; toll-like receptor adaptor molecule; transcription start site; transcription start site cluster; transthyretin; ubiquitin specific peptidase 18; ubiquitin-like modifier; voltage-gated potassium channel