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.

Details

Title
AlleleSeq: analysis of allele-specific expression and binding in a network framework
Author
Rozowsky, Joel 1 ; Abyzov, Alexej 1 ; Wang, Jing 2 ; Alves, Pedro 2 ; Raha, Debasish 3 ; Harmanci, Arif 1 ; Leng, Jing 2 ; Bjornson, Robert 4 ; Kong, Yong 5 ; Kitabayashi, Naoki 6 ; Bhardwaj, Nitin 1 ; Rubin, Mark 6 ; Snyder, Michael 7 ; Gerstein, Mark 8 

 Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, USA; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA 
 Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA 
 Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT, USA 
 Department of Computer Science, Yale University, New Haven, CT, USA; Keck Biotechnology Resource Laboratory, Yale University, New Haven, CT, USA 
 Keck Biotechnology Resource Laboratory, Yale University, New Haven, CT, USA 
 Department of Pathology and Laboratory Medicine, Weill Cornell Medical Center, New York, NY, USA 
 Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA 
 Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, USA; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA; Department of Computer Science, Yale University, New Haven, CT, USA 
Section
Article
Publication year
2011
Publication date
2011
Publisher
EMBO Press
e-ISSN
17444292
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2058914735
Copyright
© 2011. This work is published under http://creativecommons.org/licenses/by-nc-sa/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.