{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T10:52:32Z","timestamp":1740135152150,"version":"3.37.3"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,1,16]],"date-time":"2016-01-16T00:00:00Z","timestamp":1452902400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,1,16]],"date-time":"2016-01-16T00:00:00Z","timestamp":1452902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HG007358"],"award-info":[{"award-number":["R01HG007358"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HG006857"],"award-info":[{"award-number":["R01HG006857"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DA024417"],"award-info":[{"award-number":["R01DA024417"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Bioinformatics"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>As sequencing technologies can help researchers detect common and rare variants across the human genome in many individuals, it is known that jointly calling genotypes across multiple individuals based on linkage disequilibrium (LD) can facilitate the analysis of low to modest coverage sequence data. However, genotype-calling methods for family-based sequence data, particularly for complex families beyond parent-offspring trios, are still lacking.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>In this study, first, we proposed an algorithm that considers both linkage disequilibrium (LD) patterns and familial transmission in nuclear and multi-generational families while retaining the computational efficiency. Second, we extended our method to incorporate external reference panels to analyze family-based sequence data with a small sample size. In simulation studies, we show that modeling multiple offspring can dramatically increase genotype calling accuracy and reduce phasing and Mendelian errors, especially at low to modest coverage. In addition, we show that using external panels can greatly facilitate genotype calling of sequencing data with a small number of individuals. We applied our method to a whole genome sequencing study of 1339 individuals at ~10X coverage from the Minnesota Center for Twin and Family Research.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>The aggregated results show that our methods significantly outperform existing ones that ignore family constraints or LD information. We anticipate that our method will be useful for many ongoing family-based sequencing projects. We have implemented our methods efficiently in a C++ program FamLDCaller, which is available from <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.pitt.edu\/~wec47\/famldcaller.html\">http:\/\/www.pitt.edu\/~wec47\/famldcaller.html<\/jats:ext-link>.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12859-016-0880-5","type":"journal-article","created":{"date-parts":[[2016,1,16]],"date-time":"2016-01-16T03:33:45Z","timestamp":1452915225000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A computational method for genotype calling in family-based sequencing data"],"prefix":"10.1186","volume":"17","author":[{"given":"Lun-Ching","family":"Chang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bingshan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhou","family":"Fang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott","family":"Vrieze","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matt","family":"McGue","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William G.","family":"Iacono","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George C.","family":"Tseng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,1,16]]},"reference":[{"issue":"7319","key":"880_CR1","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1038\/nature09534","volume":"467","author":"G Abecasis","year":"2010","unstructured":"Abecasis G, Altshuler D, Auton A, Brooks L, Durbin R, Gibbs RA, et al. A map of human genome variation from population-scale sequencing. Nature. 2010;467(7319):1061\u201373.","journal-title":"Nature"},{"issue":"7422","key":"880_CR2","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1038\/nature11632","volume":"491","author":"C Genomes Project","year":"2012","unstructured":"Genomes Project C, Abecasis GR, Auton A, Brooks LD, DePristo MA, Durbin RM, et al. An integrated map of genetic variation from 1,092 human genomes. Nature. 2012;491(7422):56\u201365.","journal-title":"Nature"},{"issue":"7","key":"880_CR3","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1038\/nrg2989","volume":"12","author":"J Ott","year":"2011","unstructured":"Ott J, Kamatani Y, Lathrop M. Family-based designs for genome-wide association studies. Nat Rev Genet. 2011;12(7):465\u201374.","journal-title":"Nat Rev Genet"},{"issue":"5","key":"880_CR4","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1038\/nrg1839","volume":"7","author":"NM Laird","year":"2006","unstructured":"Laird NM, Lange C. Family-based designs in the age of large-scale gene-association studies. Nat Rev Genet. 2006;7(5):385\u201394.","journal-title":"Nat Rev Genet"},{"issue":"9","key":"880_CR5","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1038\/ng.646","volume":"42","author":"SB Ng","year":"2010","unstructured":"Ng SB, Bigham AW, Buckingham KJ, Hannibal MC, McMillin MJ, Gildersleeve HI, et al. Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome. Nat Genet. 2010;42(9):790\u20133.","journal-title":"Nat Genet"},{"issue":"1","key":"880_CR6","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1038\/ng.499","volume":"42","author":"SB Ng","year":"2009","unstructured":"Ng SB, Buckingham KJ, Lee C, Bigham AW, Tabor HK, Dent KM, et al. Exome sequencing identifies the cause of a mendelian disorder. Nat Genet. 2009;42(1):30\u20135.","journal-title":"Nat Genet"},{"issue":"R2","key":"880_CR7","doi-asserted-by":"publisher","first-page":"R119","DOI":"10.1093\/hmg\/ddq390","volume":"19","author":"SB Ng","year":"2010","unstructured":"Ng SB, Nickerson DA, Bamshad MJ, Shendure J. Massively parallel sequencing and rare disease. Hum Mol Genet. 2010;19(R2):R119\u201324.","journal-title":"Hum Mol Genet"},{"issue":"2","key":"880_CR8","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1002\/gepi.20449","volume":"34","author":"X Zhu","year":"2010","unstructured":"Zhu X, Feng T, Li Y, Lu Q, Elston RC. Detecting rare variants for complex traits using family and unrelated data. Genet Epidemiol. 2010;34(2):171\u201387.","journal-title":"Genet Epidemiol"},{"issue":"5978","key":"880_CR9","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1126\/science.1186802","volume":"328","author":"JC Roach","year":"2010","unstructured":"Roach JC, Glusman G, Smit AF, Huff CD, Hubley R, Shannon PT, et al. Analysis of genetic inheritance in a family quartet by whole-genome sequencing. Science. 2010;328(5978):636\u20139.","journal-title":"Science"},{"issue":"7397","key":"880_CR10","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1038\/nature10945","volume":"485","author":"SJ Sanders","year":"2012","unstructured":"Sanders SJ, Murtha MT, Gupta AR, Murdoch JD, Raubeson MJ, Willsey AJ, et al. De novo mutations revealed by whole-exome sequencing are strongly associated with autism. Nature. 2012;485(7397):237\u201341.","journal-title":"Nature"},{"issue":"7397","key":"880_CR11","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1038\/nature11011","volume":"485","author":"BM Neale","year":"2012","unstructured":"Neale BM, Kou Y, Liu L, Ma\u2019ayan A, Samocha KE, Sabo A, et al. Patterns and rates of exonic de novo mutations in autism spectrum disorders. Nature. 2012;485(7397):242\u20135.","journal-title":"Nature"},{"issue":"7397","key":"880_CR12","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1038\/nature10989","volume":"485","author":"BJ O\u2019Roak","year":"2012","unstructured":"O\u2019Roak BJ, Vives L, Girirajan S, Karakoc E, Krumm N, Coe BP, et al. Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations. Nature. 2012;485(7397):246\u201350.","journal-title":"Nature"},{"key":"880_CR13","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1038\/ejhg.2013.118","volume":"22","author":"DI Boomsma","year":"2013","unstructured":"Boomsma DI, Wijmenga C, Slagboom EP, Swertz MA, Karssen LC, Abdellaoui A, et al. The Genome of the Netherlands: design, and project goals. Eur J Hum Genet. 2013;22:221\u20137.","journal-title":"Eur J Hum Genet"},{"issue":"8","key":"880_CR14","doi-asserted-by":"publisher","first-page":"e132","DOI":"10.1371\/journal.pgen.0020132","volume":"2","author":"G Pilia","year":"2006","unstructured":"Pilia G, Chen W-M, Scuteri A, Orr\u00fa M, Albai G, Dei M, et al. Heritability of cardiovascular and personality traits in 6,148 Sardinians. PLoS Genet. 2006;2(8):e132.","journal-title":"PLoS Genet"},{"issue":"10","key":"880_CR15","doi-asserted-by":"publisher","first-page":"e1002944","DOI":"10.1371\/journal.pgen.1002944","volume":"8","author":"B Li","year":"2012","unstructured":"Li B, Chen W, Zhan X, Busonero F, Sanna S, Sidore C, et al. A likelihood-based framework for variant calling and de novo mutation detection in families. PLoS Genet. 2012;8(10):e1002944.","journal-title":"PLoS Genet"},{"issue":"10","key":"880_CR16","doi-asserted-by":"publisher","first-page":"3985","DOI":"10.1073\/pnas.1222158110","volume":"110","author":"G Peng","year":"2013","unstructured":"Peng G, Fan Y, Palculict TB, Shen P, Ruteshouser EC, Chi A-K, et al. Rare variant detection using family-based sequencing analysis. Proc Natl Acad Sci. 2013;110(10):3985\u201390.","journal-title":"Proc Natl Acad Sci"},{"issue":"1","key":"880_CR17","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1101\/gr.142455.112","volume":"23","author":"W Chen","year":"2013","unstructured":"Chen W, Li B, Zeng Z, Sanna S, Sidore C, Busonero F, et al. Genotype calling and haplotyping in parent-offspring trios. Genome Res. 2013;23(1):142\u201351.","journal-title":"Genome Res"},{"issue":"6","key":"880_CR18","doi-asserted-by":"publisher","first-page":"940","DOI":"10.1101\/gr.117259.110","volume":"21","author":"Y Li","year":"2011","unstructured":"Li Y, Sidore C, Kang HM, Boehnke M, Abecasis GR. Low-coverage sequencing: Implications for design of complex trait association studies. Genome Res. 2011;21(6):940\u201351.","journal-title":"Genome Res"},{"issue":"11","key":"880_CR19","doi-asserted-by":"publisher","first-page":"1851","DOI":"10.1101\/gr.078212.108","volume":"18","author":"H Li","year":"2008","unstructured":"Li H, Ruan J, Durbin R. Mapping short DNA sequencing reads and calling variants using mapping quality scores. Genome Res. 2008;18(11):1851\u20138.","journal-title":"Genome Res"},{"issue":"6","key":"880_CR20","doi-asserted-by":"publisher","first-page":"952","DOI":"10.1101\/gr.113084.110","volume":"21","author":"SQ Le","year":"2011","unstructured":"Le SQ, Durbin R. SNP detection and genotyping from low-coverage sequencing data on multiple diploid samples. Genome Res. 2011;21(6):952\u201360.","journal-title":"Genome Res"},{"issue":"16","key":"880_CR21","doi-asserted-by":"publisher","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","volume":"25","author":"H Li","year":"2009","unstructured":"Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, et al. The Sequence Alignment\/Map format and SAMtools. Bioinformatics. 2009;25(16):2078\u20139.","journal-title":"Bioinformatics"},{"issue":"4","key":"880_CR22","doi-asserted-by":"crossref","first-page":"2213","DOI":"10.1093\/genetics\/165.4.2213","volume":"165","author":"N Li","year":"2003","unstructured":"Li N, Stephens M. Modeling linkage disequilibrium and identifying recombination hotspots using single-nucleotide polymorphism data. Genetics. 2003;165(4):2213\u201333.","journal-title":"Genetics"},{"issue":"8","key":"880_CR23","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1002\/gepi.20533","volume":"34","author":"Y Li","year":"2010","unstructured":"Li Y, Willer CJ, Ding J, Scheet P, Abecasis GR. MaCH: using sequence and genotype data to estimate haplotypes and unobserved genotypes. Genet Epidemiol. 2010;34(8):816\u201334.","journal-title":"Genet Epidemiol"},{"issue":"7","key":"880_CR24","doi-asserted-by":"publisher","first-page":"906","DOI":"10.1038\/ng2088","volume":"39","author":"J Marchini","year":"2007","unstructured":"Marchini J, Howie B, Myers S, McVean G, Donnelly P. A new multipoint method for genome-wide association studies by imputation of genotypes. Nat Genet. 2007;39(7):906\u201313.","journal-title":"Nat Genet"},{"issue":"4","key":"880_CR25","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1086\/502802","volume":"78","author":"P Scheet","year":"2006","unstructured":"Scheet P, Stephens M. A fast and flexible statistical model for large-scale population genotype data: applications to inferring missing genotypes and haplotypic phase. Am J Hum Genet. 2006;78(4):629\u201344.","journal-title":"Am J Hum Genet"},{"issue":"2","key":"880_CR26","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1109\/5.18626","volume":"77","author":"LR Rabiner","year":"1989","unstructured":"Rabiner LR. A tutorial on hidden Markov models and selected applications in speech recognition. Proc IEEE. 1989;77(2):257\u201386.","journal-title":"Proc IEEE"},{"issue":"11","key":"880_CR27","doi-asserted-by":"publisher","first-page":"1576","DOI":"10.1101\/gr.3709305","volume":"15","author":"SF Schaffner","year":"2005","unstructured":"Schaffner SF, Foo C, Gabriel S, Reich D, Daly MJ, Altshuler D. Calibrating a coalescent simulation of human genome sequence variation. Genome Res. 2005;15(11):1576\u201383.","journal-title":"Genome Res"},{"issue":"9","key":"880_CR28","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.1101\/gr.107524.110","volume":"20","author":"A McKenna","year":"2010","unstructured":"McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A, et al. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 2010;20(9):1297\u2013303.","journal-title":"Genome Res"},{"issue":"12","key":"880_CR29","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.1111\/psyp.12350","volume":"51","author":"SI Vrieze","year":"2014","unstructured":"Vrieze SI, Malone SM, Vaidyanathan U, Kwong A, Kang HM, Zhan X, et al. In search of rare variants: preliminary results from whole genome sequencing of 1,325 individuals with psychophysiological endophenotypes. Psychophysiology. 2014;51(12):1309\u201320.","journal-title":"Psychophysiology"},{"issue":"2","key":"880_CR30","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1016\/j.ajhg.2009.01.005","volume":"84","author":"BL Browning","year":"2009","unstructured":"Browning BL, Browning SR. A unified approach to genotype imputation and haplotype-phase inference for large data sets of trios and unrelated individuals. Am J Hum Genet. 2009;84(2):210\u201323.","journal-title":"Am J Hum Genet"}],"container-title":["BMC Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12859-016-0880-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12859-016-0880-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12859-016-0880-5","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12859-016-0880-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T18:05:39Z","timestamp":1706810739000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcbioinformatics.biomedcentral.com\/articles\/10.1186\/s12859-016-0880-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,1,16]]},"references-count":30,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,12]]}},"alternative-id":["880"],"URL":"https:\/\/doi.org\/10.1186\/s12859-016-0880-5","relation":{},"ISSN":["1471-2105"],"issn-type":[{"type":"electronic","value":"1471-2105"}],"subject":[],"published":{"date-parts":[[2016,1,16]]},"assertion":[{"value":"26 August 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 January 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 January 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"37"}}