Automated classification of alternative splicing and transcriptional initiation and construction of visual database of classified patterns

MOTIVATION Large-scale detection and classification of alternative splicing and transcriptional initiation (ASTI) is the first step towards detailed studies of the functional implication and mechanisms of these phenomena. RESULTS We have developed an algorithm that classifies all observed units of ASTI into an extendable set of distinct types (e.g. cassette type) by converting a collection of alignments between a genomic DNA sequence and cDNA sequences into binary description. This description system can uniquely and compactly encode not only typical patterns but also any rare patterns that are usually collectively assigned to 'others.' More than 150 distinct ASTI types were found when this system was applied to genome-wide detection of ASTI units in human and five other eukaryotes. AVAILABILITY The data detected by this system are available through ASTRA (http://alterna.cbrc.jp/), a database equipped with a Java-based browser that can interactively reorganize the order of displayed splicing patterns on demand.

[1]  T A Thanaraj,et al.  Categorization and characterization of transcript-confirmed constitutively and alternatively spliced introns and exons from human. , 2002, Human molecular genetics.

[2]  W. Gish,et al.  Gene structure prediction and alternative splicing analysis using genomically aligned ESTs. , 2001, Genome research.

[3]  O. Gotoh,et al.  Species-specific variation of alternative splicing and transcriptional initiation in six eukaryotes. , 2005, Gene.

[4]  Makiko Suwa,et al.  An Algorithm for Classification of Alternative Splicing and Transcriptional Initiation and Its Genome-Wide Application , 2003 .

[5]  Thangavel Alphonse Thanaraj,et al.  ASD: the Alternative Splicing Database , 2004, Nucleic Acids Res..

[6]  J. Kelso,et al.  The contribution of exon-skipping events on chromosome 22 to protein coding diversity. , 2001, Genome research.

[7]  Osamu Gotoh,et al.  Homology-based gene structure prediction: simplified matching algorithm using a translated codon (tron) and improved accuracy by allowing for long gaps , 2000, Bioinform..

[8]  B. Nadal-Ginard,et al.  Alternative splicing: a ubiquitous mechanism for the generation of multiple protein isoforms from single genes. , 1987, Annual review of biochemistry.

[9]  Terry Gaasterland,et al.  Impact of alternative initiation, splicing, and termination on the diversity of the mRNA transcripts encoded by the mouse transcriptome. , 2003, Genome research.

[10]  D. Black Protein Diversity from Alternative Splicing A Challenge for Bioinformatics and Post-Genome Biology , 2000, Cell.

[11]  Y.-H. Huang,et al.  PALS db: Putative Alternative Splicing database , 2002, Nucleic Acids Res..

[12]  D. Black Mechanisms of alternative pre-messenger RNA splicing. , 2003, Annual review of biochemistry.

[13]  J. Ting,et al.  Cutting Edge: Monarch-1: A Pyrin/Nucleotide-Binding Domain/Leucine-Rich Repeat Protein That Controls Classical and Nonclassical MHC Class I Genes1 , 2003, The Journal of Immunology.

[14]  Lukas Wagner,et al.  A Greedy Algorithm for Aligning DNA Sequences , 2000, J. Comput. Biol..

[15]  J. Castle,et al.  Genome-Wide Survey of Human Alternative Pre-mRNA Splicing with Exon Junction Microarrays , 2003, Science.

[16]  Christopher J. Lee,et al.  A genomic view of alternative splicing , 2002, Nature Genetics.

[17]  Christopher J. Lee,et al.  Genome-wide detection of tissue-specific alternative splicing in the human transcriptome. , 2002, Nucleic acids research.

[18]  Dixie L Mager,et al.  Complex controls: the role of alternative promoters in mammalian genomes. , 2003, Trends in genetics : TIG.

[19]  A. Kornblihtt,et al.  Multiple links between transcription and splicing. , 2004, RNA.

[20]  Dawood B. Dudekula,et al.  Genome-wide assembly and analysis of alternative transcripts in mouse. , 2005, Genome research.

[21]  Rolf Backofen,et al.  Widespread occurrence of alternative splicing at NAGNAG acceptors contributes to proteome plasticity , 2004, Nature Genetics.

[22]  Scott R. Presnell,et al.  IL-28, IL-29 and their class II cytokine receptor IL-28R , 2002, Nature Immunology.

[23]  J. Valcárcel,et al.  Alternative pre-mRNA splicing: the logic of combinatorial control. , 2000, Trends in biochemical sciences.

[24]  Z. Wang,et al.  Products of alternatively spliced transcripts of the Wilms' tumor suppressor gene, wt1, have altered DNA binding specificity and regulate transcription in different ways. , 1995, Oncogene.

[25]  Stephen H. Bryant,et al.  CD-Search: protein domain annotations on the fly , 2004, Nucleic Acids Res..

[26]  Michael Ruogu Zhang,et al.  An alternative-exon database and its statistical analysis. , 2000, DNA and cell biology.

[27]  S. Brenner,et al.  Evidence for the widespread coupling of alternative splicing and nonsense-mediated mRNA decay in humans , 2002, Proceedings of the National Academy of Sciences of the United States of America.