{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T18:08:28Z","timestamp":1776794908459,"version":"3.51.2"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"18","license":[{"start":{"date-parts":[[2016,10,2]],"date-time":"2016-10-02T00:00:00Z","timestamp":1475366400000},"content-version":"vor","delay-in-days":2220,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/2.0\/uk\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Motivation: Determining the functional impact of non-coding disease-associated single nucleotide polymorphisms (SNPs) identified by genome-wide association studies (GWAS) is challenging. Many of these SNPs are likely to be regulatory SNPs (rSNPs): variations which affect the ability of a transcription factor (TF) to bind to DNA. However, experimental procedures for identifying rSNPs are expensive and labour intensive. Therefore, in silico methods are required for rSNP prediction. By scoring two alleles with a TF position weight matrix (PWM), it can be determined which SNPs are likely rSNPs. However, predictions in this manner are noisy and no method exists that determines the statistical significance of a nucleotide variation on a PWM score.<\/jats:p><jats:p>Results: We have designed an algorithm for in silico rSNP detection called is-rSNP. We employ novel convolution methods to determine the complete distributions of PWM scores and ratios between allele scores, facilitating assignment of statistical significance to rSNP effects. We have tested our method on 41 experimentally verified rSNPs, correctly predicting the disrupted TF in 28 cases. We also analysed 146 disease-associated SNPs with no known functional impact in an attempt to identify candidate rSNPs. Of the 11 significantly predicted disrupted TFs, 9 had previous evidence of being associated with the disease in the literature. These results demonstrate that is-rSNP is suitable for high-throughput screening of SNPs for potential regulatory function. This is a useful and important tool in the interpretation of GWAS.<\/jats:p><jats:p>Availability: is-rSNP software is available for use at: www.genomics.csse.unimelb.edu.au\/is-rSNP<\/jats:p><jats:p>Contact: \u00a0gmaci@csse.unimelb.edu.au; adam.kowalczyk@nicta.com.au<\/jats:p><jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btq378","type":"journal-article","created":{"date-parts":[[2010,9,7]],"date-time":"2010-09-07T17:41:46Z","timestamp":1283881306000},"page":"i524-i530","source":"Crossref","is-referenced-by-count":113,"title":["is-rSNP: a novel technique for<i>in silico<\/i>regulatory SNP detection"],"prefix":"10.1093","volume":"26","author":[{"given":"Geoff","family":"Macintyre","sequence":"first","affiliation":[{"name":"1 Department of Computer Science and Software Engineering, 2NICTA, Victoria Research Lab, The University of Melbourne, Victoria 3010, 3Bioinformatics and Systems Integration, The Blood and DNA Profiling Facility, Baker IDI Heart and Diabetes Institute, 75 Commercial Rd, Prahran, Victoria 3004, 4Metastasis Research Lab, Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne, Victoria 3002 and 5Department of Biochemistry and Molecular Biology. The University of Melbourne, Victoria 3010, Australia"},{"name":"1 Department of Computer Science and Software Engineering, 2NICTA, Victoria Research Lab, The University of Melbourne, Victoria 3010, 3Bioinformatics and Systems Integration, The Blood and DNA Profiling Facility, Baker IDI Heart and Diabetes Institute, 75 Commercial Rd, Prahran, Victoria 3004, 4Metastasis Research Lab, Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne, Victoria 3002 and 5Department of Biochemistry and Molecular Biology. The University of Melbourne, Victoria 3010, Australia"}]},{"given":"James","family":"Bailey","sequence":"additional","affiliation":[{"name":"1 Department of Computer Science and Software Engineering, 2NICTA, Victoria Research Lab, The University of Melbourne, Victoria 3010, 3Bioinformatics and Systems Integration, The Blood and DNA Profiling Facility, Baker IDI Heart and Diabetes Institute, 75 Commercial Rd, Prahran, Victoria 3004, 4Metastasis Research Lab, Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne, Victoria 3002 and 5Department of Biochemistry and Molecular Biology. The University of Melbourne, Victoria 3010, Australia"},{"name":"1 Department of Computer Science and Software Engineering, 2NICTA, Victoria Research Lab, The University of Melbourne, Victoria 3010, 3Bioinformatics and Systems Integration, The Blood and DNA Profiling Facility, Baker IDI Heart and Diabetes Institute, 75 Commercial Rd, Prahran, Victoria 3004, 4Metastasis Research Lab, Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne, Victoria 3002 and 5Department of Biochemistry and Molecular Biology. The University of Melbourne, Victoria 3010, Australia"}]},{"given":"Izhak","family":"Haviv","sequence":"additional","affiliation":[{"name":"1 Department of Computer Science and Software Engineering, 2NICTA, Victoria Research Lab, The University of Melbourne, Victoria 3010, 3Bioinformatics and Systems Integration, The Blood and DNA Profiling Facility, Baker IDI Heart and Diabetes Institute, 75 Commercial Rd, Prahran, Victoria 3004, 4Metastasis Research Lab, Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne, Victoria 3002 and 5Department of Biochemistry and Molecular Biology. The University of Melbourne, Victoria 3010, Australia"},{"name":"1 Department of Computer Science and Software Engineering, 2NICTA, Victoria Research Lab, The University of Melbourne, Victoria 3010, 3Bioinformatics and Systems Integration, The Blood and DNA Profiling Facility, Baker IDI Heart and Diabetes Institute, 75 Commercial Rd, Prahran, Victoria 3004, 4Metastasis Research Lab, Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne, Victoria 3002 and 5Department of Biochemistry and Molecular Biology. The University of Melbourne, Victoria 3010, Australia"},{"name":"1 Department of Computer Science and Software Engineering, 2NICTA, Victoria Research Lab, The University of Melbourne, Victoria 3010, 3Bioinformatics and Systems Integration, The Blood and DNA Profiling Facility, Baker IDI Heart and Diabetes Institute, 75 Commercial Rd, Prahran, Victoria 3004, 4Metastasis Research Lab, Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne, Victoria 3002 and 5Department of Biochemistry and Molecular Biology. The University of Melbourne, Victoria 3010, Australia"}]},{"given":"Adam","family":"Kowalczyk","sequence":"additional","affiliation":[{"name":"1 Department of Computer Science and Software Engineering, 2NICTA, Victoria Research Lab, The University of Melbourne, Victoria 3010, 3Bioinformatics and Systems Integration, The Blood and DNA Profiling Facility, Baker IDI Heart and Diabetes Institute, 75 Commercial Rd, Prahran, Victoria 3004, 4Metastasis Research Lab, Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne, Victoria 3002 and 5Department of Biochemistry and Molecular Biology. The University of Melbourne, Victoria 3010, Australia"},{"name":"1 Department of Computer Science and Software Engineering, 2NICTA, Victoria Research Lab, The University of Melbourne, Victoria 3010, 3Bioinformatics and Systems Integration, The Blood and DNA Profiling Facility, Baker IDI Heart and Diabetes Institute, 75 Commercial Rd, Prahran, Victoria 3004, 4Metastasis Research Lab, Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne, Victoria 3002 and 5Department of Biochemistry and Molecular Biology. The University of Melbourne, Victoria 3010, Australia"}]}],"member":"286","published-online":{"date-parts":[[2010,9,4]]},"reference":[{"key":"2023012508280100200_B1","doi-asserted-by":"crossref","first-page":"e5","DOI":"10.1371\/journal.pcbi.0040005","article-title":"In silico detection of sequence variations modifying transcriptional regulation","volume":"4","author":"Andersen","year":"2008","journal-title":"PLoS Comput. 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