{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T16:42:25Z","timestamp":1776184945123,"version":"3.50.1"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Motivation: Expression quantitative trait loci (eQTL) studies have discovered thousands of genetic variants that regulate gene expression, enabling a better understanding of the functional role of non-coding sequences. However, eQTL studies are costly, requiring large sample sizes and genome-wide genotyping of each sample. In contrast, analysis of allele-specific expression (ASE) is becoming a popular approach to detect the effect of genetic variation on gene expression, even within a single individual. This is typically achieved by counting the number of RNA-seq reads matching each allele at heterozygous sites and testing the null hypothesis of a 1:1 allelic ratio. In principle, when genotype information is not readily available, it could be inferred from the RNA-seq reads directly. However, there are currently no existing methods that jointly infer genotypes and conduct ASE inference, while considering uncertainty in the genotype calls.<\/jats:p>\n                  <jats:p>Results: We present QuASAR, quantitative allele-specific analysis of reads, a novel statistical learning method for jointly detecting heterozygous genotypes and inferring ASE. The proposed ASE inference step takes into consideration the uncertainty in the genotype calls, while including parameters that model base-call errors in sequencing and allelic over-dispersion. We validated our method with experimental data for which high-quality genotypes are available. Results for an additional dataset with multiple replicates at different sequencing depths demonstrate that QuASAR is a powerful tool for ASE analysis when genotypes are not available.<\/jats:p>\n                  <jats:p>Availability and implementation: \u00a0http:\/\/github.com\/piquelab\/QuASAR.<\/jats:p>\n                  <jats:p>Contact: \u00a0fluca@wayne.edu or rpique@wayne.edu<\/jats:p>\n                  <jats:p>Supplementary information: \u00a0Supplementary Material is available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btu802","type":"journal-article","created":{"date-parts":[[2014,12,5]],"date-time":"2014-12-05T21:51:31Z","timestamp":1417816291000},"page":"1235-1242","source":"Crossref","is-referenced-by-count":75,"title":["QuASAR: quantitative allele-specific analysis of reads"],"prefix":"10.1093","volume":"31","author":[{"given":"Chris T.","family":"Harvey","sequence":"first","affiliation":[{"name":"1 Center for Molecular Medicine and Genetics, Department of Obstetrics and Gynecology, Wayne State University, 540\u2009E Canfield, Scott Hall, Detroit, MI 48201, USA and 2Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory A.","family":"Moyerbrailean","sequence":"additional","affiliation":[{"name":"1 Center for Molecular Medicine and Genetics, Department of Obstetrics and Gynecology, Wayne State University, 540\u2009E Canfield, Scott Hall, Detroit, MI 48201, USA and 2Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gordon O.","family":"Davis","sequence":"additional","affiliation":[{"name":"1 Center for Molecular Medicine and Genetics, Department of Obstetrics and Gynecology, Wayne State University, 540\u2009E Canfield, Scott Hall, Detroit, MI 48201, USA and 2Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoquan","family":"Wen","sequence":"additional","affiliation":[{"name":"1 Center for Molecular Medicine and Genetics, Department of Obstetrics and Gynecology, Wayne State University, 540\u2009E Canfield, Scott Hall, Detroit, MI 48201, USA and 2Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Luca","sequence":"additional","affiliation":[{"name":"1 Center for Molecular Medicine and Genetics, Department of Obstetrics and Gynecology, Wayne State University, 540\u2009E Canfield, Scott Hall, Detroit, MI 48201, USA and 2Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roger","family":"Pique-Regi","sequence":"additional","affiliation":[{"name":"1 Center for Molecular Medicine and Genetics, Department of Obstetrics and Gynecology, Wayne State University, 540\u2009E Canfield, Scott Hall, Detroit, MI 48201, USA and 2Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2014,12,4]]},"reference":[{"key":"2023051309022084100_btu802-B1","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1073\/pnas.1115761109","article-title":"Deciphering the genetic architecture of variation in the immune response to Mycobacterium tuberculosis infection","volume":"109","author":"Barreiro","year":"2012","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023051309022084100_btu802-B2","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1038\/ng.2416","article-title":"Breast cancer risk-associated SNPs modulate the affinity of chromatin for FOXA1 and alter gene expression","volume":"44","author":"Cowper-Sal lari","year":"2012","journal-title":"Nat. Genet."},{"key":"2023051309022084100_btu802-B3","doi-asserted-by":"crossref","first-page":"3207","DOI":"10.1093\/bioinformatics\/btp579","article-title":"Effect of read-mapping biases on detecting allele-specific expression from RNA-sequencing data","volume":"25","author":"Degner","year":"2009","journal-title":"Bioinformatics"},{"key":"2023051309022084100_btu802-B4","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1038\/nature10808","article-title":"DNaseI sensitivity QTLs are a major determinant of human expression variation","volume":"482","author":"Degner","year":"2012","journal-title":"Nature"},{"key":"2023051309022084100_btu802-B5","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/ng.806","article-title":"A framework for variation discovery and genotyping using next-generation DNA sequencing data","volume":"43","author":"DePristo","year":"2011","journal-title":"Nat. Genet."},{"key":"2023051309022084100_btu802-B6","doi-asserted-by":"crossref","DOI":"10.1038\/nrg3115","article-title":"Cellular genomics for complex traits","author":"Dermitzakis","year":"2012"},{"key":"2023051309022084100_btu802-B7","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1126\/science.1174148","article-title":"Common regulatory variation impacts gene expression in a cell type-dependent manner","volume":"325","author":"Dimas","year":"2009","journal-title":"Science"},{"key":"2023051309022084100_btu802-B8","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1016\/j.ajhg.2010.10.024","article-title":"Gene expression in skin and lymphoblastoid cells: refined statistical method reveals extensive overlap in cis-eQTL signals","volume":"87","author":"Ding","year":"2010","journal-title":"Am. J. Hum. Genet."},{"key":"2023051309022084100_btu802-B9","doi-asserted-by":"crossref","first-page":"S6","DOI":"10.1186\/1471-2164-13-S2-S6","article-title":"Towards accurate detection and genotyping of expressed variants from whole transcriptome sequencing data","volume":"13","author":"Duitama","year":"2012","journal-title":"BMC Genomics"},{"key":"2023051309022084100_btu802-B10","doi-asserted-by":"crossref","first-page":"1246949","DOI":"10.1126\/science.1246949","article-title":"Innate immune activity conditions the effect of regulatory variants upon monocyte gene expression","volume":"343","author":"Fairfax","year":"2014","journal-title":"Science"},{"key":"2023051309022084100_btu802-B11","doi-asserted-by":"crossref","first-page":"e1000952","DOI":"10.1371\/journal.pgen.1000952","article-title":"Abundant quantitative trait loci exist for DNA methylation and gene expression in human brain","volume":"6","author":"Gibbs","year":"2010","journal-title":"PLoS Genet."},{"key":"2023051309022084100_btu802-B12","doi-asserted-by":"crossref","first-page":"e1000282","DOI":"10.1371\/journal.pgen.1000282","article-title":"Genetics meets metabolomics: a genome-wide association study of metabolite profiles in human serum","volume":"4","author":"Gieger","year":"2008","journal-title":"PLoS Genet."},{"key":"2023051309022084100_btu802-B13","doi-asserted-by":"crossref","first-page":"e1001279","DOI":"10.1371\/journal.pgen.1001279","article-title":"Global analysis of the impact of environmental perturbation on cis-regulation of gene expression","volume":"7","author":"Grundberg","year":"2011","journal-title":"PLoS Genet."},{"key":"2023051309022084100_btu802-B14","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1186\/1471-2164-15-471","article-title":"Allele-specific expression and eQTL analysis in mouse adipose tissue","volume":"15","author":"Hasin-Brumshtein","year":"2014","journal-title":"BMC Genomics"},{"key":"2023051309022084100_btu802-B15","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1126\/science.1183621","article-title":"Variation in transcription factor binding among humans","volume":"328","author":"Kasowski","year":"2010","journal-title":"Science"},{"key":"2023051309022084100_btu802-B16","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1038\/nmeth.1528","article-title":"Analysis and design of RNA sequencing experiments for identifying isoform regulation","volume":"7","author":"Katz","year":"2010","journal-title":"Nat. Methods"},{"key":"2023051309022084100_btu802-B17","doi-asserted-by":"crossref","first-page":"e1004304","DOI":"10.1371\/journal.pgen.1004304","article-title":"Allelic expression of deleterious protein-coding variants across human tissues","volume":"10","author":"Kukurba","year":"2014","journal-title":"PLoS Genet."},{"key":"2023051309022084100_btu802-B18","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1038\/nature12531","article-title":"Transcriptome and genome sequencing uncovers functional variation in humans","volume":"501","author":"Lappalainen","year":"2013","journal-title":"Nature"},{"key":"2023051309022084100_btu802-B19","doi-asserted-by":"crossref","first-page":"1246980","DOI":"10.1126\/science.1246980","article-title":"Common genetic variants modulate pathogen-sensing responses in human dendritic cells","volume":"343","author":"Lee","year":"2014","journal-title":"Science"},{"key":"2023051309022084100_btu802-B20","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","article-title":"Fast and accurate short read alignment with Burrows-Wheeler transform","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"2023051309022084100_btu802-B21","doi-asserted-by":"crossref","first-page":"e1002162","DOI":"10.1371\/journal.pgen.1002162","article-title":"Interactions between glucocorticoid treatment and cis-regulatory polymorphisms contribute to cellular response phenotypes","volume":"7","author":"Maranville","year":"2011","journal-title":"PLoS Genet."},{"key":"2023051309022084100_btu802-B22","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1126\/science.1184655","article-title":"Heritable individual-specific and allele-specific chromatin signatures in humans","volume":"328","author":"McDaniell","year":"2010","journal-title":"Science"},{"key":"2023051309022084100_btu802-B23","volume":"Vol. 382","author":"McLachlan","year":"2007","journal-title":"The EM Algorithm and Extensions"},{"key":"2023051309022084100_btu802-B24","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1126\/science.1242429","article-title":"Identification of genetic variants that affect histone modifications in human cells","volume":"342","author":"McVicker","year":"2013","journal-title":"Science"},{"key":"2023051309022084100_btu802-B25","doi-asserted-by":"crossref","first-page":"e1000072","DOI":"10.1371\/journal.pgen.1000072","article-title":"A genome-wide association study identifies protein quantitative trait loci (pQTLs)","volume":"4","author":"Melzer","year":"2008","journal-title":"PLoS Genet."},{"key":"2023051309022084100_btu802-B26","doi-asserted-by":"crossref","first-page":"e1000895","DOI":"10.1371\/journal.pgen.1000895","article-title":"Candidate causal regulatory effects by integration of expression QTLs with complex trait genetic associations","volume":"6","author":"Nica","year":"2010","journal-title":"PLoS Genet."},{"key":"2023051309022084100_btu802-B27","doi-asserted-by":"crossref","first-page":"e1002003","DOI":"10.1371\/journal.pgen.1002003","article-title":"The architecture of gene regulatory variation across multiple human tissues: the MuTHER study","volume":"7","author":"Nica","year":"2011","journal-title":"PLoS Genet."},{"key":"2023051309022084100_btu802-B28","doi-asserted-by":"crossref","first-page":"e1000888","DOI":"10.1371\/journal.pgen.1000888","article-title":"Trait-associated SNPs are more likely to be eQTLs: annotation to enhance discovery from GWAS","volume":"6","author":"Nicolae","year":"2010","journal-title":"PLoS Genet."},{"key":"2023051309022084100_btu802-B29","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1038\/nrg2815","article-title":"Genome-wide allele-specific analysis: insights into regulatory variation","volume":"11","author":"Pastinen","year":"2010","journal-title":"Nat. Rev. Genet."},{"key":"2023051309022084100_btu802-B30","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1038\/nature08872","article-title":"Understanding mechanisms underlying human gene expression variation with RNA sequencing","volume":"464","author":"Pickrell","year":"2010","journal-title":"Nature"},{"key":"2023051309022084100_btu802-B31","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1016\/j.ajhg.2013.08.008","article-title":"Reliable identification of genomic variants from RNA-seq data","volume":"93","author":"Piskol","year":"2013","journal-title":"Am. J. Hum. Genet."},{"key":"2023051309022084100_btu802-B32","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1101\/gr.131201.111","article-title":"Effects of sequence variation on differential allelic transcription factor occupancy and gene expression","volume":"22","author":"Reddy","year":"2012","journal-title":"Genome Res."},{"key":"2023051309022084100_btu802-B33","doi-asserted-by":"crossref","first-page":"3032","DOI":"10.1093\/bioinformatics\/btl521","article-title":"Maximum likelihood inference of imprinting and allele-specific expression from EST data","volume":"22","author":"Seoighe","year":"2006","journal-title":"Bioinformatics"},{"key":"2023051309022084100_btu802-B34","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1038\/nature08489","article-title":"Mutational evolution in a lobular breast tumour profiled at single nucleotide resolution","volume":"461","author":"Shah","year":"2009","journal-title":"Nature"},{"key":"2023051309022084100_btu802-B35","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1101\/gr.119784.110","article-title":"A powerful and flexible statistical framework for testing hypotheses of allele-specific gene expression from RNA-seq data","volume":"21","author":"Skelly","year":"2011","journal-title":"Genome Res."},{"key":"2023051309022084100_btu802-B36","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1038\/nature07940","article-title":"Genetic analysis of radiation-induced changes in human gene expression","volume":"459","author":"Smirnov","year":"2009","journal-title":"Nature"},{"key":"2023051309022084100_btu802-B37","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1111\/1467-9868.00346","article-title":"A direct approach to false discovery rates","volume":"64","author":"Storey","year":"2002","journal-title":"J. R. Stat. Soc. Ser. B Stat. Methodol."},{"key":"2023051309022084100_btu802-B38","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1038\/ng2142","article-title":"Population genomics of human gene expression","volume":"39","author":"Stranger","year":"2007","journal-title":"Nat. Genet."},{"key":"2023051309022084100_btu802-B39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1541-0420.2011.01654.x","article-title":"A statistical framework for eQTL mapping using RNA-seq data","volume":"68","author":"Sun","year":"2012","journal-title":"Biometrics"},{"key":"2023051309022084100_btu802-B40","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1038\/nbt.1621","article-title":"Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation","volume":"28","author":"Trapnell","year":"2010","journal-title":"Nat. Biotechnol."},{"key":"2023051309022084100_btu802-B41","article-title":"Cross-population meta-analysis of eQTLs: fine mapping and functional study","author":"Wen","year":"2014","journal-title":"bioRxiv"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/31\/8\/1235\/50305925\/bioinformatics_31_8_1235.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/31\/8\/1235\/50305925\/bioinformatics_31_8_1235.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,13]],"date-time":"2023-05-13T05:03:52Z","timestamp":1683954232000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/31\/8\/1235\/212555"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,12,4]]},"references-count":41,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2015,4,15]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btu802","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/007492","asserted-by":"object"}]},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2015,4,15]]},"published":{"date-parts":[[2014,12,4]]}}}