title: novoSNP, a novel computational tool for sequence variation discovery.
abstract: Technological improvements shifted sequencing from low-throughput, work-intensive, gel-based systems to high-throughput capillary systems. This resulted in a broad use of genomic resequencing to identify sequence variations in genes and regulatory, as well as extended genomic regions. We describe a software package, novoSNP, that conscientiously discovers single nucleotide polymorphisms (SNPs) and insertion-deletion polymorphisms (INDELs) in sequence trace files in a fast, reliable, and user-friendly way. We compared the performance of novoSNP with that of PolyPhred and PolyBayes on two data sets. The first data set comprised 1028 sequence trace files obtained from diagnostic mutation analyses of SCN1A (neuronal voltage-gated sodium channel alpha-subunit type I gene). The second data set comprised 9062 sequence trace files from a genomic resequencing project aiming at the construction of a high-density SNP map of MAPT (microtubule-associated protein tau gene). Visual inspection of these data sets had identified 38 sequence variations for SCN1A and 488 for MAPT. novoSNP automatically identified all 38 SCN1A variations including five INDELs, while for MAPT only 15 of the 488 variations were not correctly marked. PolyPhred detected far fewer SNPs as compared to novoSNP and missed nearly all INDELs. PolyBayes, designed for the sequence analysis of cloned templates, detected only a limited number of the variations present in the data set. Besides the significant improvement in the automated detection of sequence variations both in diagnostic mutation analyses and in SNP discovery projects, novoSNP also offers a user-friendly interface for inspecting possible genetic variations.
authors.affiliation: Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Antwerpen, Belgium.
authors.forename: Stefan
authors.initials: S
authors.lastname: Weckx
authors.forename: Jurgen
authors.initials: J
authors.lastname: Del-Favero
authors.forename: Rosa
authors.initials: R
authors.lastname: Rademakers
authors.forename: Lieve
authors.initials: L
authors.lastname: Claes
authors.forename: Marc
authors.initials: M
authors.lastname: Cruts
authors.forename: Peter
authors.initials: P
authors.lastname: De Jonghe
authors.forename: Christine
authors.initials: C
authors.lastname: Van Broeckhoven
authors.forename: Peter
authors.initials: P
authors.lastname: De Rijk
mesh_terms: D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D014644:Genetic Variation; D023281:Genomics / Q000379:methods* / Q000706:statistics & numerical data; D006801:Humans; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D012984:Software
chemical_list: D004247:DNA
references.citation: Nat Genet. 1999 Dec;23(4):452-6
references.pmid: 10581034
references.citation: Bioinformatics. 2005 Feb 1;21(3):385-7
references.pmid: 15347573
references.citation: Nucleic Acids Res. 2001 Jan 1;29(1):308-11
references.pmid: 11125122
references.citation: Science. 2001 Feb 16;291(5507):1304-51
references.pmid: 11181995
references.citation: Nature. 2001 Feb 15;409(6822):860-921
references.pmid: 11237011
references.citation: Nature. 2001 Feb 15;409(6822):928-33
references.pmid: 11237013
references.citation: Am J Hum Genet. 2001 Jun;68(6):1327-32
references.pmid: 11359211
references.citation: Nature. 2002 Dec 5;420(6915):520-62
references.pmid: 12466850
references.citation: Hum Mutat. 2003 Jun;21(6):615-21
references.pmid: 12754708
references.citation: Nucleic Acids Res. 2004 Jan 1;32(Database issue):D516-9
references.pmid: 14681471
references.citation: Nucleic Acids Res. 2004 Jul 1;32(Web Server issue):W170-2
references.pmid: 15215373
references.citation: J Mol Biol. 1990 Oct 5;215(3):403-10
references.pmid: 2231712
references.citation: Genomics. 1994 Sep 1;23(1):138-44
references.pmid: 7829062
references.citation: Nucleic Acids Res. 1997 Jul 15;25(14):2745-51
references.pmid: 9207020
references.citation: Genome Res. 1998 Mar;8(3):175-85
references.pmid: 9521921
references.citation: Genome Res. 1998 Mar;8(3):186-94
references.pmid: 9521922
references.citation: Science. 1998 Dec 11;282(5396):2012-8
references.pmid: 9851916
references.citation: Science. 2000 Mar 24;287(5461):2185-95
references.pmid: 10731132