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ARG-walker: inference of individual specific strengths of meiotic recombination hotspots by population genomics analysis

BACKGROUND: 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 pol...

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Autores principales: Chen, Hao, Yang, Peng, Guo, Jing, Kwoh, Chee Keong, Przytycka, Teresa M, Zheng, Jie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4682399/
https://www.ncbi.nlm.nih.gov/pubmed/26679564
http://dx.doi.org/10.1186/1471-2164-16-S12-S1
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author Chen, Hao
Yang, Peng
Guo, Jing
Kwoh, Chee Keong
Przytycka, Teresa M
Zheng, Jie
author_facet Chen, Hao
Yang, Peng
Guo, Jing
Kwoh, Chee Keong
Przytycka, Teresa M
Zheng, Jie
author_sort Chen, Hao
collection PubMed
description BACKGROUND: 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.
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spelling pubmed-46823992015-12-21 ARG-walker: inference of individual specific strengths of meiotic recombination hotspots by population genomics analysis Chen, Hao Yang, Peng Guo, Jing Kwoh, Chee Keong Przytycka, Teresa M Zheng, Jie BMC Genomics Research BACKGROUND: 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. BioMed Central 2015-12-09 /pmc/articles/PMC4682399/ /pubmed/26679564 http://dx.doi.org/10.1186/1471-2164-16-S12-S1 Text en Copyright © 2015 Chen et al. http://creativecommons.org/licenses/by/4.0 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.
spellingShingle Research
Chen, Hao
Yang, Peng
Guo, Jing
Kwoh, Chee Keong
Przytycka, Teresa M
Zheng, Jie
ARG-walker: inference of individual specific strengths of meiotic recombination hotspots by population genomics analysis
title ARG-walker: inference of individual specific strengths of meiotic recombination hotspots by population genomics analysis
title_full ARG-walker: inference of individual specific strengths of meiotic recombination hotspots by population genomics analysis
title_fullStr ARG-walker: inference of individual specific strengths of meiotic recombination hotspots by population genomics analysis
title_full_unstemmed ARG-walker: inference of individual specific strengths of meiotic recombination hotspots by population genomics analysis
title_short ARG-walker: inference of individual specific strengths of meiotic recombination hotspots by population genomics analysis
title_sort arg-walker: inference of individual specific strengths of meiotic recombination hotspots by population genomics analysis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4682399/
https://www.ncbi.nlm.nih.gov/pubmed/26679564
http://dx.doi.org/10.1186/1471-2164-16-S12-S1
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