Characterization and prediction of alternative splice sites.

Human alternative isoform, cryptic, skipped, and constitutive splice sites from the ALTEXTRON database were analysed regarding splice site strength, composition, GC content, position and binding site strength of polypyrimidine tract and branch site. Several features were identified which distinguish alternative isoform and cryptic splice sites, but not skipped splice sites from constitutive ones. These include splice site strength, introns GC content, U2AF35 binding site score, and oligonucleotide frequencies. For the predictive classification of splice sites, pattern recognition models for different splicing factor binding sites and oligonucleotide frequency models (OFMs) were combined using backpropagation networks. 67.45% of acceptor sites and 71.23% of donor sites are correctly classified by networks trained for classification of constitutive and alternative isoform/cryptic splice sites. A web-application for the prediction of alternative splice sites is available at http://es.embnet.org/~mwang/assp.html .

[1]  Simon Cawley,et al.  HMM sampling and applications to gene finding and alternative splicing , 2003, ECCB.

[2]  A. Krainer,et al.  Listening to silence and understanding nonsense: exonic mutations that affect splicing , 2002, Nature Reviews Genetics.

[3]  T A Thanaraj,et al.  Prediction and statistical analysis of alternatively spliced exons. , 2003, Progress in molecular and subcellular biology.

[4]  Christopher J. Lee,et al.  Genome-wide detection of alternative splicing in expressed sequences of human genes , 2001, Nucleic Acids Res..

[5]  Luciano Milanesi,et al.  10 – Prediction of Human Gene Structure , 1998 .

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

[7]  Martin J. Bishop,et al.  Guide to Human Genome Computing , 1994 .

[8]  Susan M. Berget,et al.  An Intronic Splicing Enhancer Binds U1 snRNPs To Enhance Splicing and Select 5′ Splice Sites , 2000, Molecular and Cellular Biology.

[9]  G. Bernardi,et al.  The human genome: organization and evolutionary history. , 1995, Annual review of genetics.

[10]  T. D. Schneider,et al.  Information content of individual genetic sequences. , 1997, Journal of theoretical biology.

[11]  Martin Vingron,et al.  Increase of functional diversity by alternative splicing. , 2003, Trends in genetics : TIG.

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

[13]  Temple F. Smith,et al.  Prediction of gene structure. , 1992, Journal of molecular biology.

[14]  Michael R. Green,et al.  Functional recognition of the 3′ splice site AG by the splicing factor U2AF35 , 1999, Nature.

[15]  Alexander E Vinogradov,et al.  Isochores and tissue-specificity. , 2003, Nucleic acids research.

[16]  Ron Shamir,et al.  A non-EST-based method for exon-skipping prediction. , 2004, Genome research.

[17]  Robert F. RoscignoSBlI,et al.  A Mutational Analysis of the Polypyrimidine Tract of Introns , 1993 .

[18]  M. Gelfand,et al.  Frequent alternative splicing of human genes. , 1999, Genome research.

[19]  C Saccone,et al.  Isochore specificity of AUG initiator context of human genes , 1999, FEBS letters.

[20]  J. Valcárcel,et al.  Dual Function for U2AF35 in AG-Dependent Pre-mRNA Splicing , 2001, Molecular and Cellular Biology.

[21]  J. G. Patton,et al.  Functional analysis of the polypyrimidine tract in pre-mRNA splicing. , 1997, Nucleic acids research.

[22]  J. Bouck,et al.  Genetic selection for balanced retroviral splicing: novel regulation involving the second step can be mediated by transitions in the polypyrimidine tract , 1995, Molecular and cellular biology.

[23]  M. Garcia-Blanco,et al.  A mutational analysis of the polypyrimidine tract of introns. Effects of sequence differences in pyrimidine tracts on splicing. , 1993, The Journal of biological chemistry.

[24]  S. Karlin,et al.  Prediction of complete gene structures in human genomic DNA. , 1997, Journal of molecular biology.

[25]  Ming D. Li,et al.  Correlations Between mRNA Expression Levels and GC Contents of Coding and Untranslated Regions of Genes in Rodents , 2002, Journal of Molecular Evolution.

[26]  Ron Shamir,et al.  Accurate identification of alternatively spliced exons using support vector machine , 2005, Bioinform..

[27]  B. Graveley.  Alternative splicing: increasing diversity in the proteomic world. , 2001, Trends in genetics : TIG.

[28]  A. J. Lopez,et al.  Alternative splicing of pre-mRNA: developmental consequences and mechanisms of regulation. , 1998, Annual review of genetics.

[29]  N L Harris,et al.  Splice junctions, branch point sites, and exons: sequence statistics, identification, and applications to genome project. , 1990, Methods in enzymology.

[30]  Martin Vingron,et al.  SpliceNest: visualizing gene structure and alternative splicing based on EST clusters , 2002 .

[31]  J. Valcárcel,et al.  Distinct binding specificities and functions of higher eukaryotic polypyrimidine tract-binding proteins. , 1995, Science.

[32]  W. Johnson,et al.  Diffusion mechanisms in metallic supercooled liquids and glasses , 1999, Nature.

[33]  L. Duret,et al.  Determinants of CpG islands: expression in early embryo and isochore structure. , 2001, Genome research.

[34]  L. Duret,et al.  Nature and structure of human genes that generate retropseudogenes. , 2000, Genome research.

[35]  David Haussler,et al.  A Generalized Hidden Markov Model for the Recognition of Human Genes in DNA , 1996, ISMB.

[36]  Luciano Milanesi,et al.  GeneBuilder: interactive in silico prediction of gene structure , 1999, Bioinform..

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