title: Topological Data Analysis Generates High-Resolution, Genome-wide Maps of Human Recombination.
abstract: Meiotic recombination is a fundamental evolutionary process driving diversity in eukaryotes. In mammals, recombination is known to occur preferentially at specific genomic regions. Using topological data analysis (TDA), a branch of applied topology that extracts global features from large data sets, we developed an efficient method for mapping recombination at fine scales. When compared to standard linkage-based methods, TDA can deal with a larger number of SNPs and genomes without incurring prohibitive computational costs. We applied TDA to 1,000 Genomes Project data and constructed high-resolution whole-genome recombination maps of seven human populations. Our analysis shows that recombination is generally under-represented within transcription start sites. However, the binding sites of specific transcription factors are enriched for sites of recombination. These include transcription factors that regulate the expression of meiosis- and gametogenesis-specific genes, cell cycle progression, and differentiation blockage. Additionally, our analysis identifies an enrichment for sites of recombination at repeat-derived loci matched by piwi-interacting RNAs.
authors.affiliation: Department of Systems Biology, Columbia University College of Physicians and Surgeons, 1130 St. Nicholas Avenue, New York, NY 10032, USA; Department of Biomedical Informatics, Columbia University College of Physicians and Surgeons, 1130 St. Nicholas Avenue, New York, NY 10032, USA. Electronic address: pg2495@cumc.columbia.edu.
authors.forename: Pablo G
authors.initials: PG
authors.lastname: Camara
authors.affiliation: Department of Systems Biology, Columbia University College of Physicians and Surgeons, 1130 St. Nicholas Avenue, New York, NY 10032, USA; Department of Biomedical Informatics, Columbia University College of Physicians and Surgeons, 1130 St. Nicholas Avenue, New York, NY 10032, USA.
authors.forename: Daniel I S
authors.initials: DI
authors.lastname: Rosenbloom
authors.affiliation: Department of Systems Biology, Columbia University College of Physicians and Surgeons, 1130 St. Nicholas Avenue, New York, NY 10032, USA; Department of Physics, Columbia University, New York, NY 10027, USA.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Emmett
authors.affiliation: The Simons Center for Systems Biology, Institute for Advanced Study, Princeton, NJ 08540, USA.
authors.forename: Arnold J
authors.initials: AJ
authors.lastname: Levine
authors.affiliation: Department of Systems Biology, Columbia University College of Physicians and Surgeons, 1130 St. Nicholas Avenue, New York, NY 10032, USA; Department of Biomedical Informatics, Columbia University College of Physicians and Surgeons, 1130 St. Nicholas Avenue, New York, NY 10032, USA. Electronic address: rr2579@cumc.columbia.edu.
authors.forename: Raul
authors.initials: R
authors.lastname: Rabadan
mesh_terms: D002874:Chromosome Mapping; D008040:Genetic Linkage; D015894:Genome, Human; D055106:Genome-Wide Association Study; D059765:Homologous Recombination; D006801:Humans; D008540:Meiosis; D020641:Polymorphism, Single Nucleotide