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 personaliz...

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Main Authors: Joel Rozowsky, Alexej Abyzov, Jing Wang, Pedro Alves, Debasish Raha, Arif Harmanci, Jing Leng, Robert Bjornson, Yong Kong, Naoki Kitabayashi, Nitin Bhardwaj, Mark Rubin, Michael Snyder, Mark Gerstein
Format: Article
Language:English
Published: Springer Nature 2011-08-01
Series:Molecular Systems Biology
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Online Access:https://doi.org/10.1038/msb.2011.54
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author Joel Rozowsky
Alexej Abyzov
Jing Wang
Pedro Alves
Debasish Raha
Arif Harmanci
Jing Leng
Robert Bjornson
Yong Kong
Naoki Kitabayashi
Nitin Bhardwaj
Mark Rubin
Michael Snyder
Mark Gerstein
author_facet Joel Rozowsky
Alexej Abyzov
Jing Wang
Pedro Alves
Debasish Raha
Arif Harmanci
Jing Leng
Robert Bjornson
Yong Kong
Naoki Kitabayashi
Nitin Bhardwaj
Mark Rubin
Michael Snyder
Mark Gerstein
author_sort Joel Rozowsky
collection DOAJ
description 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.
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spelling doaj-art-a03e5035eab84ba3903acc1d4f4b2bfb2025-08-20T02:11:49ZengSpringer NatureMolecular Systems Biology1744-42922011-08-017111510.1038/msb.2011.54AlleleSeq: analysis of allele‐specific expression and binding in a network frameworkJoel Rozowsky0Alexej Abyzov1Jing Wang2Pedro Alves3Debasish Raha4Arif Harmanci5Jing Leng6Robert Bjornson7Yong Kong8Naoki Kitabayashi9Nitin Bhardwaj10Mark Rubin11Michael Snyder12Mark Gerstein13Program in Computational Biology and Bioinformatics, Yale UniversityProgram in Computational Biology and Bioinformatics, Yale UniversityDepartment of Molecular Biophysics and Biochemistry, Yale UniversityDepartment of Molecular Biophysics and Biochemistry, Yale UniversityDepartment of Molecular, Cellular, and Developmental Biology, Yale UniversityProgram in Computational Biology and Bioinformatics, Yale UniversityDepartment of Molecular Biophysics and Biochemistry, Yale UniversityDepartment of Computer Science, Yale UniversityKeck Biotechnology Resource Laboratory, Yale UniversityDepartment of Pathology and Laboratory Medicine, Weill Cornell Medical CenterProgram in Computational Biology and Bioinformatics, Yale UniversityDepartment of Pathology and Laboratory Medicine, Weill Cornell Medical CenterDepartment of Genetics, Stanford University School of MedicineProgram in Computational Biology and Bioinformatics, Yale UniversityAbstract 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.https://doi.org/10.1038/msb.2011.54allele‐specificChIP‐SeqnetworksRNA‐Seq
spellingShingle Joel Rozowsky
Alexej Abyzov
Jing Wang
Pedro Alves
Debasish Raha
Arif Harmanci
Jing Leng
Robert Bjornson
Yong Kong
Naoki Kitabayashi
Nitin Bhardwaj
Mark Rubin
Michael Snyder
Mark Gerstein
AlleleSeq: analysis of allele‐specific expression and binding in a network framework
Molecular Systems Biology
allele‐specific
ChIP‐Seq
networks
RNA‐Seq
title AlleleSeq: analysis of allele‐specific expression and binding in a network framework
title_full AlleleSeq: analysis of allele‐specific expression and binding in a network framework
title_fullStr AlleleSeq: analysis of allele‐specific expression and binding in a network framework
title_full_unstemmed AlleleSeq: analysis of allele‐specific expression and binding in a network framework
title_short AlleleSeq: analysis of allele‐specific expression and binding in a network framework
title_sort alleleseq analysis of allele specific expression and binding in a network framework
topic allele‐specific
ChIP‐Seq
networks
RNA‐Seq
url https://doi.org/10.1038/msb.2011.54
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