FASTSNP: an always up-to-date and extendable service for SNP function analysis and prioritization

Single nucleotide polymorphism (SNP) prioritization based on the phenotypic risk is essential for association studies. Assessment of the risk requires access to a variety of heterogeneous biological databases and analytical tools. FASTSNP (function analysis and selection tool for single nucleotide polymorphisms) is a web server that allows users to efficiently identify and prioritize high-risk SNPs according to their phenotypic risks and putative functional effects. A unique feature of FASTSNP is that the functional effect information used for SNP prioritization is always up-to-date, because FASTSNP extracts the information from 11 external web servers at query time using a team of web wrapper agents. Moreover, FASTSNP is extendable by simply deploying more Web wrapper agents. To validate the results of our prioritization, we analyzed 1569 SNPs from the SNP500Cancer database. The results show that SNPs with a high predicted risk exhibit low allele frequencies for the minor alleles, consistent with a well-known finding that a strong selective pressure exists for functional polymorphisms. We have been using FASTSNP for 2 years and FASTSNP enables us to discover a novel promoter polymorphism. FASTSNP is available at .

[1]  Tam P. Sneddon,et al.  The HUGO Gene Nomenclature Database, 2006 updates , 2005, Nucleic Acids Res..

[2]  Margaret A. Pericak-Vance,et al.  SNPselector: a web tool for selecting SNPs for genetic association studies , 2005, Bioinform..

[3]  Daniel J. Blankenberg,et al.  Galaxy: a platform for interactive large-scale genome analysis. , 2005, Genome research.

[4]  M. Charng,et al.  A novel functional VKORC1 promoter polymorphism is associated with inter-individual and inter-ethnic differences in warfarin sensitivity. , 2005, Human molecular genetics.

[5]  K. Lindblad-Toh,et al.  Systematic discovery of regulatory motifs in human promoters and 3′ UTRs by comparison of several mammals , 2005, Nature.

[6]  Chia-Hui Chang,et al.  Reconfigurable Web wrapper agents for biological information integration , 2005, J. Assoc. Inf. Sci. Technol..

[7]  G. Stormo,et al.  PolyMAPr: Programs for polymorphism database mining, annotation, and functional analysis , 2005, Human Mutation.

[8]  Tatiana Tatusova,et al.  NCBI Reference Sequence (RefSeq): a curated non-redundant sequence database of genomes, transcripts and proteins , 2004, Nucleic Acids Res..

[9]  Tatiana A. Tatusova,et al.  NCBI Reference Sequence (RefSeq): a curated non-redundant sequence database of genomes, transcripts and proteins , 2004, Nucleic Acids Res..

[10]  Gene W. Yeo,et al.  Systematic Identification and Analysis of Exonic Splicing Silencers , 2004, Cell.

[11]  Matthias Wjst,et al.  BMC Bioinformatics Methodology article Target SNP selection in complex disease association studies , 2004 .

[12]  Christopher B. Burge,et al.  RESCUE-ESE identifies candidate exonic splicing enhancers in vertebrate exons , 2004, Nucleic Acids Res..

[13]  Thomas L. Madden,et al.  BLAST: at the core of a powerful and diverse set of sequence analysis tools , 2004, Nucleic Acids Res..

[14]  Joaquín Dopazo,et al.  PupaSNP Finder: a web tool for finding SNPs with putative effect at transcriptional level , 2004, Nucleic Acids Res..

[15]  Simon C. Potter,et al.  An overview of Ensembl. , 2004, Genome research.

[16]  L. Prokunina,et al.  Regulatory SNPs in complex diseases: their identification and functional validation , 2004, Expert Reviews in Molecular Medicine.

[17]  Toshihiro Tanaka The International HapMap Project , 2003, Nature.

[18]  Jinhua Wang,et al.  ESEfinder: a web resource to identify exonic splicing enhancers , 2003, Nucleic Acids Res..

[19]  R. Jonsson,et al.  A regulatory polymorphism in PDCD1 is associated with susceptibility to systemic lupus erythematosus in humans , 2002, Nature Genetics.

[20]  Alberto Riva,et al.  SNPper: retrieval and analysis of human SNPs , 2002, Bioinform..

[21]  P. Bork,et al.  Human non-synonymous SNPs: server and survey. , 2002, Nucleic acids research.

[22]  Enrico Motta,et al.  Configuring Online Problem-Solving Resources with the Internet Reasoning Service , 2002, Intelligent Information Processing.

[23]  R. Myers,et al.  Candidate-gene approaches for studying complex genetic traits: practical considerations , 2002, Nature Reviews Genetics.

[24]  A. Krainer,et al.  Disruption of an SF2/ASF-dependent exonic splicing enhancer in SMN2 causes spinal muscular atrophy in the absence of SMN1 , 2002, Nature Genetics.

[25]  P. Bork,et al.  Towards a structural basis of human non-synonymous single nucleotide polymorphisms. , 2000, Trends in genetics : TIG.

[26]  K. Sirotkin,et al.  dbSNP-database for single nucleotide polymorphisms and other classes of minor genetic variation. , 1999, Genome research.

[27]  Chun-Nan Hsu,et al.  Generating Finite-State Transducers for Semi-Structured Data Extraction from the Web , 1998, Inf. Syst..

[28]  Brian Staats,et al.  SNP500Cancer: a public resource for sequence validation and assay development for genetic variation in candidate genes , 2004, Nucleic Acids Res..

[29]  David L. Wheeler,et al.  GenBank: update , 2004, Nucleic Acids Res..

[30]  Maria Jesus Martin,et al.  The SWISS-PROT protein knowledgebase and its supplement TrEMBL in 2003 , 2003, Nucleic Acids Res..

[31]  Terrence S. Furey,et al.  The UCSC Genome Browser Database , 2003, Nucleic Acids Res..

[32]  Chia-Hui Chang,et al.  Reconfigurable Web Wrapper Agents for Web Information Integration , 2003, IIWeb.

[33]  Carlos Alberto Heuser,et al.  Integrating Biological Databases , 2003, SBBD.

[34]  MiningChun-Nan Hsu Finite-state Transducers for Semi-structured Text Mining , 1999 .

[35]  E. Lander,et al.  Characterization of single-nucleotide polymorphisms in coding regions of human genes , 1999, Nature Genetics.

[36]  T. Heinemeyer,et al.  Databases on transcriptional regulation : TRANSFAC , TRRD and COMPEL , 1997 .