title: A Bayesian approach for estimating allele-specific expression from RNA-Seq data with diploid genomes.
abstract: BACKGROUND
  RNA-sequencing (RNA-Seq) has become a popular tool for transcriptome profiling in mammals. However, accurate estimation of allele-specific expression (ASE) based on alignments of reads to the reference genome is challenging, because it contains only one allele on a mosaic haploid genome. Even with the information of diploid genome sequences, precise alignment of reads to the correct allele is difficult because of the high-similarity between the corresponding allele sequences.
  
  
  RESULTS
  We propose a Bayesian approach to estimate ASE from RNA-Seq data with diploid genome sequences. In the statistical framework, the haploid choice is modeled as a hidden variable and estimated simultaneously with isoform expression levels by variational Bayesian inference. Through the simulation data analysis, we demonstrate the effectiveness of the proposed approach in terms of identifying ASE compared to the existing approach. We also show that our approach enables better quantification of isoform expression levels compared to the existing methods, TIGAR2, RSEM and Cufflinks. In the real data analysis of the human reference lymphoblastoid cell line GM12878, some autosomal genes were identified as ASE genes, and skewed paternal X-chromosome inactivation in GM12878 was identified.
  
  
  CONCLUSIONS
  The proposed method, called ASE-TIGAR, enables accurate estimation of gene expression from RNA-Seq data in an allele-specific manner. Our results show the effectiveness of utilizing personal genomic information for accurate estimation of ASE. An implementation of our method is available at http://nagasakilab.csml.org/ase-tigar .
authors.affiliation: Present address: Institute for Genomic Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, 92093, California, USA. nnariai@ucsd.edu.|Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan. nnariai@ucsd.edu.
authors.forename: Naoki
authors.initials: N
authors.lastname: Nariai
authors.affiliation: Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan. kojima@megabank.tohoku.ac.jp.
authors.forename: Kaname
authors.initials: K
authors.lastname: Kojima
authors.affiliation: Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan. mimori@megabank.tohoku.ac.jp.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Mimori
authors.affiliation: Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan. kawai@megabank.tohoku.ac.jp.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Kawai
authors.affiliation: Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan. nagasaki@megabank.tohoku.ac.jp.
authors.forename: Masao
authors.initials: M
authors.lastname: Nagasaki
mesh_terms: D000465:Algorithms; D000483:Alleles; D001499:Bayes Theorem; D045744:Cell Line, Tumor; D004171:Diploidy; D005786:Gene Expression Regulation; D015894:Genome, Human; D006801:Humans; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012313:RNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017423:Sequence Analysis, RNA
chemical_list: D020033:Protein Isoforms; D011506:Proteins; D012313:RNA
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