PERFECTOS-APE - Predicting Regulatory Functional Effect of SNPs by Approximate P-value Estimation

Ilya E. Vorontsov, Ivan V. Kulakovskiy, Grigory Khimulya, Daria D. Nikolaeva, Vsevolod J. Makeev


Single nucleotide polymorphisms (SNPs) and variants (SNVs) are often found in regulatory regions of human genome. Nucleotide substitutions in promoter and enhancer regions may affect transcription factor (TF) binding and alter gene expression regulation. Nowadays binding patterns are known for hundreds of human TFs. Thus one can assess possible functional effects of allele variations or mutations in TF binding sites using sequence analysis. We present PERFECTOS-APE, the software to PrEdict Regulatory Functional Effect of SNPs by Approximate P-value Estimation. Using a predefined collection of position weight matrices (PWMs) representing TF binding patterns, PERFECTOS-APE identifies transcription factors whose binding sites can be significantly affected by given nucleotide substitutions. PERFECTOS-APE supports both classic PWMs under the position independency assumption, and dinucleotide PWMs accounting for the dinucleotide composition and correlations between nucleotides in adjacent positions within binding sites. PERFECTOS-APE uses dynamic programming to calculate PWM score distribution and convert the scores to P-values with an optional binary search mode using a precomputed P-value list to speed-up the computations. Software is written in Java and is freely available as standalone program and online tool: We have tested our algorithm on several disease associated SNVs as well as on a set of cancer somatic mutations occurring in intronic regions of the human genome.


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Paper Citation

in Harvard Style

E. Vorontsov I., V. Kulakovskiy I., Khimulya G., D. Nikolaeva D. and J. Makeev V. (2015). PERFECTOS-APE - Predicting Regulatory Functional Effect of SNPs by Approximate P-value Estimation . In Proceedings of the International Conference on Bioinformatics Models, Methods and Algorithms - Volume 1: BIOINFORMATICS, (BIOSTEC 2015) ISBN 978-989-758-070-3, pages 102-108. DOI: 10.5220/0005189301020108

in Bibtex Style

author={Ilya E. Vorontsov and Ivan V. Kulakovskiy and Grigory Khimulya and Daria D. Nikolaeva and Vsevolod J. Makeev},
title={PERFECTOS-APE - Predicting Regulatory Functional Effect of SNPs by Approximate P-value Estimation},
booktitle={Proceedings of the International Conference on Bioinformatics Models, Methods and Algorithms - Volume 1: BIOINFORMATICS, (BIOSTEC 2015)},

in EndNote Style

JO - Proceedings of the International Conference on Bioinformatics Models, Methods and Algorithms - Volume 1: BIOINFORMATICS, (BIOSTEC 2015)
TI - PERFECTOS-APE - Predicting Regulatory Functional Effect of SNPs by Approximate P-value Estimation
SN - 978-989-758-070-3
AU - E. Vorontsov I.
AU - V. Kulakovskiy I.
AU - Khimulya G.
AU - D. Nikolaeva D.
AU - J. Makeev V.
PY - 2015
SP - 102
EP - 108
DO - 10.5220/0005189301020108