Multi-platform discovery of haplotype-resolved structural variation in human genomes.

Autor: Chaisson MJP; Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, 98195, USA.; Quantitative and Computational Biology, University of Southern California, Los Angeles, CA, 90089, USA., Sanders AD; European Molecular Biology Laboratory, Genome Biology Unit, 69117, Heidelberg, Germany., Zhao X; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, 48109, USA.; Center for Genomic Medicine, Massachusetts General Hospital, Department of Neurology, Harvard Medical School, Boston, MA, 02114, USA., Malhotra A; The Jackson Laboratory for Genomic Medicine, Farmington, CT, 06032, USA., Porubsky D; European Research Institute for the Biology of Ageing, University of Groningen, University Medical Centre Groningen, Groningen, AV, NL-9713, The Netherlands.; Center for Bioinformatics, Saarland University and the Max Planck Institute for Informatics, 66123, Saarbrücken, Germany., Rausch T; European Molecular Biology Laboratory, Genome Biology Unit, 69117, Heidelberg, Germany., Gardner EJ; Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, 21201, USA., Rodriguez OL; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Guo L; The School of Life Science and Technology of Xi'an Jiaotong University, 710049, Xi'an, China.; MOE Key Lab for Intelligent Networks & Networks Security, School of Electronics and Information Engineering, Xi'an Jiaotong University, 710049, Xi'an, China.; Ye-Lab For Omics and Omics Informatics, Xi'an Jiaotong University, 710049, Xi'an, China., Collins RL; Center for Genomic Medicine, Massachusetts General Hospital, Department of Neurology, Harvard Medical School, Boston, MA, 02114, USA.; Program in Bioinformatics and Integrative Genomics, Harvard Medical School, Boston, MA, 02115, USA., Fan X; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA., Wen J; Department of Bioinformatics and Genomics, College of Computing and Informatics, The University of North Carolina at Charlotte, Charlotte, NC, 28223, USA., Handsaker RE; Department of Genetics, Harvard Medical School, Boston, MA, 02115, USA.; The Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA., Fairley S; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SD, United Kingdom., Kronenberg ZN; Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, 98195, USA., Kong X; Yale University Medical School, Computational Biology and Bioinformatics Program, New Haven, CT, 06520, USA.; Department of Molecular Biophysics and Biochemistry, Yale University, 266 Whitney Avenue, New Haven, CT, 06520, USA., Hormozdiari F; Biochemistry and Molecular Medicine, University of California Davis, Davis, CA, 95616, USA.; UC Davis Genome Center, University of California, Davis, Davis, CA, 95616, USA., Lee D; USTAR Center for Genetic Discovery and Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT, 84112, USA., Wenger AM; Pacific Biosciences, Menlo Park, CA, 94025, USA., Hastie AR; Bionano Genomics, San Diego, CA, 92121, USA., Antaki D; Beyster Center for Genomics of Psychiatric Diseases, Department of Psychiatry University of California San Diego, La Jolla, CA, 92093, USA., Anantharaman T; Bionano Genomics, San Diego, CA, 92121, USA., Audano PA; Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, 98195, USA., Brand H; Center for Genomic Medicine, Massachusetts General Hospital, Department of Neurology, Harvard Medical School, Boston, MA, 02114, USA., Cantsilieris S; Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, 98195, USA., Cao H; Bionano Genomics, San Diego, CA, 92121, USA., Cerveira E; The Jackson Laboratory for Genomic Medicine, Farmington, CT, 06032, USA., Chen C; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA., Chen X; Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, 21201, USA., Chin CS; Pacific Biosciences, Menlo Park, CA, 94025, USA., Chong Z; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA., Chuang NT; Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, 21201, USA., Lambert CC; Pacific Biosciences, Menlo Park, CA, 94025, USA., Church DM; 10X Genomics, Pleasanton, CA, 94566, USA., Clarke L; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SD, United Kingdom., Farrell A; USTAR Center for Genetic Discovery and Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT, 84112, USA., Flores J; Illumina Clinical Services Laboratory, Illumina, Inc., 5200 Illumina Way, San Diego, CA, 92122, USA., Galeev T; Yale University Medical School, Computational Biology and Bioinformatics Program, New Haven, CT, 06520, USA.; Department of Molecular Biophysics and Biochemistry, Yale University, 266 Whitney Avenue, New Haven, CT, 06520, USA., Gorkin DU; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, 92093, USA.; Ludwig Institute for Cancer Research, La Jolla, CA, 92093, USA., Gujral M; Beyster Center for Genomics of Psychiatric Diseases, Department of Psychiatry University of California San Diego, La Jolla, CA, 92093, USA., Guryev V; European Research Institute for the Biology of Ageing, University of Groningen, University Medical Centre Groningen, Groningen, AV, NL-9713, The Netherlands., Heaton WH; 10X Genomics, Pleasanton, CA, 94566, USA., Korlach J; Pacific Biosciences, Menlo Park, CA, 94025, USA., Kumar S; Yale University Medical School, Computational Biology and Bioinformatics Program, New Haven, CT, 06520, USA.; Department of Molecular Biophysics and Biochemistry, Yale University, 266 Whitney Avenue, New Haven, CT, 06520, USA., Kwon JY; The Jackson Laboratory for Genomic Medicine, Farmington, CT, 06032, USA.; Department of Graduate Studies - Life Sciences, Ewha Womans University, 52, Ewhayeodae-gil, Seodaemun-gu, Seoul, 03760, South Korea., Lam ET; Bionano Genomics, San Diego, CA, 92121, USA., Lee JE; DNA Link, Seodaemun-gu, Seoul, South Korea., Lee J; Bionano Genomics, San Diego, CA, 92121, USA., Lee WP; The Jackson Laboratory for Genomic Medicine, Farmington, CT, 06032, USA., Lee SP; TreeCode Sdn Bhd, Bandar Botanic, 41200, Klang, Malaysia., Li S; Yale University Medical School, Computational Biology and Bioinformatics Program, New Haven, CT, 06520, USA.; Department of Molecular Biophysics and Biochemistry, Yale University, 266 Whitney Avenue, New Haven, CT, 06520, USA., Marks P; 10X Genomics, Pleasanton, CA, 94566, USA., Viaud-Martinez K; Illumina Clinical Services Laboratory, Illumina, Inc., 5200 Illumina Way, San Diego, CA, 92122, USA., Meiers S; European Molecular Biology Laboratory, Genome Biology Unit, 69117, Heidelberg, Germany., Munson KM; Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, 98195, USA., Navarro FCP; Yale University Medical School, Computational Biology and Bioinformatics Program, New Haven, CT, 06520, USA.; Department of Molecular Biophysics and Biochemistry, Yale University, 266 Whitney Avenue, New Haven, CT, 06520, USA., Nelson BJ; Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, 98195, USA., Nodzak C; Department of Bioinformatics and Genomics, College of Computing and Informatics, The University of North Carolina at Charlotte, Charlotte, NC, 28223, USA., Noor A; Beyster Center for Genomics of Psychiatric Diseases, Department of Psychiatry University of California San Diego, La Jolla, CA, 92093, USA., Kyriazopoulou-Panagiotopoulou S; 10X Genomics, Pleasanton, CA, 94566, USA., Pang AWC; Bionano Genomics, San Diego, CA, 92121, USA., Qiu Y; Ludwig Institute for Cancer Research, La Jolla, CA, 92093, USA.; Bioinformatics and Systems Biology Graduate Program, University of California, San Diego, La Jolla, CA, 92093, USA., Rosanio G; Beyster Center for Genomics of Psychiatric Diseases, Department of Psychiatry University of California San Diego, La Jolla, CA, 92093, USA., Ryan M; The Jackson Laboratory for Genomic Medicine, Farmington, CT, 06032, USA., Stütz A; European Molecular Biology Laboratory, Genome Biology Unit, 69117, Heidelberg, Germany., Spierings DCJ; European Research Institute for the Biology of Ageing, University of Groningen, University Medical Centre Groningen, Groningen, AV, NL-9713, The Netherlands., Ward A; USTAR Center for Genetic Discovery and Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT, 84112, USA., Welch AE; Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, 98195, USA., Xiao M; School of Biomedical Engineering, Drexel University, Philadelphia, PA, 19104, USA., Xu W; 10X Genomics, Pleasanton, CA, 94566, USA., Zhang C; The Jackson Laboratory for Genomic Medicine, Farmington, CT, 06032, USA., Zhu Q; The Jackson Laboratory for Genomic Medicine, Farmington, CT, 06032, USA., Zheng-Bradley X; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SD, United Kingdom., Lowy E; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SD, United Kingdom., Yakneen S; European Molecular Biology Laboratory, Genome Biology Unit, 69117, Heidelberg, Germany., McCarroll S; Department of Genetics, Harvard Medical School, Boston, MA, 02115, USA.; The Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA., Jun G; Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, 77225, USA., Ding L; Department of Medicine, McDonnell Genome Institute, Siteman Cancer Center, Washington University School of Medicine, St. Louis, MI, 63108, USA., Koh CL; High Impact Research, University of Malaya, 50603, Kuala Lumpur, Malaysia., Ren B; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, 92093, USA.; Ludwig Institute for Cancer Research, La Jolla, CA, 92093, USA., Flicek P; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SD, United Kingdom., Chen K; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA., Gerstein MB; Yale University Medical School, Computational Biology and Bioinformatics Program, New Haven, CT, 06520, USA.; Department of Molecular Biophysics and Biochemistry, Yale University, 266 Whitney Avenue, New Haven, CT, 06520, USA.; Department of Computer Science, Yale University, 266 Whitney Avenue, New Haven, CT, 06520, USA.; Department of Statistics and Data Science, Yale University, 266 Whitney Avenue, New Haven, CT, 06520, USA., Kwok PY; Institute for Human Genetics, University of California-San Francisco, San Francisco, CA, 94143, USA., Lansdorp PM; European Research Institute for the Biology of Ageing, University of Groningen, University Medical Centre Groningen, Groningen, AV, NL-9713, The Netherlands.; Terry Fox Laboratory, BC Cancer Agency, Vancouver, BC, V5Z 1L3, Canada.; Department of Medical Genetics, University of British Columbia, Vancouver, BC, V6T 1Z4, Canada., Marth GT; USTAR Center for Genetic Discovery and Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT, 84112, USA., Sebat J; Beyster Center for Genomics of Psychiatric Diseases, Department of Psychiatry University of California San Diego, La Jolla, CA, 92093, USA.; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, 92093, USA.; Department of Pediatrics, University of California San Diego, La Jolla, CA, 92093, USA., Shi X; Department of Bioinformatics and Genomics, College of Computing and Informatics, The University of North Carolina at Charlotte, Charlotte, NC, 28223, USA., Bashir A; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Ye K; MOE Key Lab for Intelligent Networks & Networks Security, School of Electronics and Information Engineering, Xi'an Jiaotong University, 710049, Xi'an, China.; Ye-Lab For Omics and Omics Informatics, Xi'an Jiaotong University, 710049, Xi'an, China.; The First Affiliated Hospital of Xi'an Jiaotong University, 710061, Xi'an, China., Devine SE; Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, 21201, USA., Talkowski ME; Center for Genomic Medicine, Massachusetts General Hospital, Department of Neurology, Harvard Medical School, Boston, MA, 02114, USA.; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.; Center for Mendelian Genomics, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA., Mills RE; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, 48109, USA.; Department of Human Genetics, University of Michigan, Ann Arbor, MI, 48109, USA., Marschall T; Center for Bioinformatics, Saarland University and the Max Planck Institute for Informatics, 66123, Saarbrücken, Germany., Korbel JO; European Molecular Biology Laboratory, Genome Biology Unit, 69117, Heidelberg, Germany. jan.korbel@embl.de.; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SD, United Kingdom. jan.korbel@embl.de., Eichler EE; Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, 98195, USA. eee@gs.washington.edu.; Howard Hughes Medical Institute, University of Washington, Seattle, WA, 98195, USA. eee@gs.washington.edu., Lee C; The Jackson Laboratory for Genomic Medicine, Farmington, CT, 06032, USA. charles.lee@jax.org.; Department of Graduate Studies - Life Sciences, Ewha Womans University, 52, Ewhayeodae-gil, Seodaemun-gu, Seoul, 03760, South Korea. charles.lee@jax.org.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2019 Apr 16; Vol. 10 (1), pp. 1784. Date of Electronic Publication: 2019 Apr 16.
DOI: 10.1038/s41467-018-08148-z
Abstrakt: The incomplete identification of structural variants (SVs) from whole-genome sequencing data limits studies of human genetic diversity and disease association. Here, we apply a suite of long-read, short-read, strand-specific sequencing technologies, optical mapping, and variant discovery algorithms to comprehensively analyze three trios to define the full spectrum of human genetic variation in a haplotype-resolved manner. We identify 818,054 indel variants (<50 bp) and 27,622 SVs (≥50 bp) per genome. We also discover 156 inversions per genome and 58 of the inversions intersect with the critical regions of recurrent microdeletion and microduplication syndromes. Taken together, our SV callsets represent a three to sevenfold increase in SV detection compared to most standard high-throughput sequencing studies, including those from the 1000 Genomes Project. The methods and the dataset presented serve as a gold standard for the scientific community allowing us to make recommendations for maximizing structural variation sensitivity for future genome sequencing studies.
Databáze: MEDLINE