title: AlleleSeq: analysis of allele-specific expression and binding in a network framework.
abstract: To study allele-specific expression (ASE) and binding (ASB), that is, differences between the maternally and paternally derived alleles, we have developed a computational pipeline (AlleleSeq). Our pipeline initially constructs a diploid personal genome sequence (and corresponding personalized gene annotation) using genomic sequence variants (SNPs, indels, and structural variants), and then identifies allele-specific events with significant differences in the number of mapped reads between maternal and paternal alleles. There are many technical challenges in the construction and alignment of reads to a personal diploid genome sequence that we address, for example, bias of reads mapping to the reference allele. We have applied AlleleSeq to variation data for NA12878 from the 1000 Genomes Project as well as matched, deeply sequenced RNA-Seq and ChIP-Seq data sets generated for this purpose. In addition to observing fairly widespread allele-specific behavior within individual functional genomic data sets (including results consistent with X-chromosome inactivation), we can study the interaction between ASE and ASB. Furthermore, we investigate the coordination between ASE and ASB from multiple transcription factors events using a regulatory network framework. Correlation analyses and network motifs show mostly coordinated ASB and ASE.
authors.affiliation: Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA. joel.rozowsky@yale.edu
authors.forename: Joel
authors.initials: J
authors.lastname: Rozowsky
authors.forename: Alexej
authors.initials: A
authors.lastname: Abyzov
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Pedro
authors.initials: P
authors.lastname: Alves
authors.forename: Debasish
authors.initials: D
authors.lastname: Raha
authors.forename: Arif
authors.initials: A
authors.lastname: Harmanci
authors.forename: Jing
authors.initials: J
authors.lastname: Leng
authors.forename: Robert
authors.initials: R
authors.lastname: Bjornson
authors.forename: Yong
authors.initials: Y
authors.lastname: Kong
authors.forename: Naoki
authors.initials: N
authors.lastname: Kitabayashi
authors.forename: Nitin
authors.initials: N
authors.lastname: Bhardwaj
authors.forename: Mark
authors.initials: M
authors.lastname: Rubin
authors.forename: Michael
authors.initials: M
authors.lastname: Snyder
authors.forename: Mark
authors.initials: M
authors.lastname: Gerstein
mesh_terms: D000483:Alleles; D002460:Cell Line; D002874:Chromosome Mapping; D041321:Chromosomes, Human, X / Q000235:genetics; D041322:Chromosomes, Human, Y / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D030541:Databases, Genetic; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D015894:Genome, Human; D006801:Humans; D058977:Molecular Sequence Annotation; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D017423:Sequence Analysis, RNA; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D014157:Transcription Factors