title: GeneiASE: Detection of condition-dependent and static allele-specific expression from RNA-seq data without haplotype information.
abstract: Allele-specific expression (ASE) is the imbalance in transcription between maternal and paternal alleles at a locus and can be probed in single individuals using massively parallel DNA sequencing technology. Assessing ASE within a single sample provides a static picture of the ASE, but the magnitude of ASE for a given transcript may vary between different biological conditions in an individual. Such condition-dependent ASE could indicate a genetic variation with a functional role in the phenotypic difference. We investigated ASE through RNA-sequencing of primary white blood cells from eight human individuals before and after the controlled induction of an inflammatory response, and detected condition-dependent and static ASE at 211 and 13021 variants, respectively. We developed a method, GeneiASE, to detect genes exhibiting static or condition-dependent ASE in single individuals. GeneiASE performed consistently over a range of read depths and ASE effect sizes, and did not require phasing of variants to estimate haplotypes. We observed condition-dependent ASE related to the inflammatory response in 19 genes, and static ASE in 1389 genes. Allele-specific expression was confirmed by validation of variants through real-time quantitative RT-PCR, with RNA-seq and RT-PCR ASE effect-size correlations r = 0.67 and r = 0.94 for static and condition-dependent ASE, respectively.
authors.affiliation: KTH Royal Institute of Technology, Science for Life Laboratory, School of Biotechnology, Division of Gene Technology, SE-171 65, Solna, Sweden.
authors.forename: Daniel
authors.initials: D
authors.lastname: Edsgärd
authors.affiliation: Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Center for Molecular Medicine, and Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden.|KTH Royal Institute of Technology, Science for Life Laboratory, School of Biotechnology, Division of Proteomics, SE-171 65, Solna, Sweden.
authors.forename: Maria Jesus
authors.initials: MJ
authors.lastname: Iglesias
authors.affiliation: Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Center for Molecular Medicine, and Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Sarah-Jayne
authors.initials: SJ
authors.lastname: Reilly
authors.affiliation: Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Center for Molecular Medicine, and Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Hamsten
authors.affiliation: Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Tornvall
authors.affiliation: Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Center for Molecular Medicine, and Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden.|KTH Royal Institute of Technology, Science for Life Laboratory, School of Biotechnology, Division of Proteomics, SE-171 65, Solna, Sweden.|Department of Medicine, Centre for Hematology, Karolinska University Hospital and Karolinska Institutet, Solna, Sweden.
authors.forename: Jacob
authors.initials: J
authors.lastname: Odeberg
authors.affiliation: KTH Royal Institute of Technology, Science for Life Laboratory, School of Biotechnology, Division of Gene Technology, SE-171 65, Solna, Sweden.
authors.forename: Olof
authors.initials: O
authors.lastname: Emanuelsson
mesh_terms: D000483:Alleles; D022981:Allelic Imbalance; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007962:Leukocytes; D008297:Male