dc.contributor.authorChen, Hao
dc.contributor.authorYang, Peng
dc.contributor.authorGuo, Jing
dc.contributor.authorKwoh, Chee Keong
dc.contributor.authorPrzytycka, Teresa M.
dc.contributor.authorZheng, Jie
dc.identifier.citationChen, H., Yang, P., Guo, J., Kwoh, C. K., Przytycka, T. M., & Zheng, J. (2015). ARG-walker: inference of individual specific strengths of meiotic recombination hotspots by population genomics analysis. BMC Genomics, 16(Suppl 12), S1-.en_US
dc.description.abstractBackground: Meiotic recombination hotspots play important roles in various aspects of genomics, but the underlying mechanisms for regulating the locations and strengths of recombination hotspots are not yet fully revealed. Most existing algorithms for estimating recombination rates from sequence polymorphism data can only output average recombination rates of a population, although there is evidence for the heterogeneity in recombination rates among individuals. For genome-wide association studies (GWAS) of recombination hotspots, an efficient algorithm that estimates the individualized strengths of recombination hotspots is highly desirable. Results: In this work, we propose a novel graph mining algorithm named ARG-walker, based on random walks on ancestral recombination graphs (ARG), to estimate individual-specific recombination hotspot strengths. Extensive simulations demonstrate that ARG-walker is able to distinguish the hot allele of a recombination hotspot from the cold allele. Integrated with output of ARG-walker, we performed GWAS on the phased haplotype data of the 22 autosome chromosomes of the HapMap Asian population samples of Chinese and Japanese (JPT+CHB). Significant cis-regulatory signals have been detected, which is corroborated by the enrichment of the well-known 13-mer motif CCNCCNTNNCCNC of PRDM9 protein. Moreover, two new DNA motifs have been identified in the flanking regions of the significantly associated SNPs (single nucleotide polymorphisms), which are likely to be new cis-regulatory elements of meiotic recombination hotspots of the human genome. Conclusions: Our results on both simulated and real data suggest that ARG-walker is a promising new method for estimating the individual recombination variations. In the future, it could be used to uncover the mechanisms of recombination regulation and human diseases related with recombination hotspots.en_US
dc.description.sponsorshipMOE (Min. of Education, S’pore)en_US
dc.format.extent10 p.en_US
dc.relation.ispartofseriesBMC Genomicsen_US
dc.rights© 2015 Chen et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.en_US
dc.subjectMeiotic recombination hotspoten_US
dc.subjectIndividual recombination strengthen_US
dc.titleARG-walker: inference of individual specific strengths of meiotic recombination hotspots by population genomics analysisen_US
dc.typeJournal Article
dc.contributor.schoolSchool of Computer Engineeringen_US
dc.description.versionPublished versionen_US

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