Scalable probabilistic PCA for large-scale genetic variation data
Autoři:
Aman Agrawal aff001; Alec M. Chiu aff002; Minh Le aff003; Eran Halperin aff002; Sriram Sankararaman aff002; Eran Halperin aff003; Sriram Sankararaman aff003
Působiště autorů:
Department of Computer Science, Indian Institute of Technology, Delhi, India
aff001; Bioinformatics Interdepartmental Program, University of California, Los Angeles, California, United States of America
aff002; Bioinformatics Interdepartmental Program, University of California, Los Angeles, California United States of America
aff002; Department of Computer Science, University of California, Los Angeles, California, United States of America
aff003; Department of Computer Science, University of California, Los Angeles, California United States of America
aff003; Department of Human Genetics, University of California, Los Angeles, California, United States of America
aff004; Department of Human Genetics, University of California, Los Angeles, California United States of America
aff004; Department of Anesthesiology and Perioperative Medicine, University of California, Los Angeles, California, United States of America
aff005; Department of Anesthesiology and Perioperative Medicine, University of California, Los Angeles, California United States of America
aff005; Department of Computational Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, United States of America
aff006; Department of Computational Medicine, David Geffen School of Medicine, University of California, Los Angeles, California United States of America
aff006; Institute of Precision Health, University of California, Los Angeles, California, United States of America
aff007
Vyšlo v časopise:
Scalable probabilistic PCA for large-scale genetic variation data. PLoS Genet 16(5): e32767. doi:10.1371/journal.pgen.1008773
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pgen.1008773
Souhrn
Principal component analysis (PCA) is a key tool for understanding population structure and controlling for population stratification in genome-wide association studies (GWAS). With the advent of large-scale datasets of genetic variation, there is a need for methods that can compute principal components (PCs) with scalable computational and memory requirements. We present ProPCA, a highly scalable method based on a probabilistic generative model, which computes the top PCs on genetic variation data efficiently. We applied ProPCA to compute the top five PCs on genotype data from the UK Biobank, consisting of 488,363 individuals and 146,671 SNPs, in about thirty minutes. To illustrate the utility of computing PCs in large samples, we leveraged the population structure inferred by ProPCA within White British individuals in the UK Biobank to identify several novel genome-wide signals of recent putative selection including missense mutations in RPGRIP1L and TLR4.
Klíčová slova:
Algorithms – Genome-wide association studies – Genomic signal processing – Genomics statistics – Molecular genetics – principal component analysis – Singular value decomposition – Variant genotypes
Zdroje
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