AlleleSeq: Analysis of allele-specific expression and binding in a network framework

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

Research output: Contribution to journalArticle

171 Scopus citations

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.

Original languageEnglish (US)
Article number522
JournalMolecular Systems Biology
Volume7
DOIs
StatePublished - 2011

Keywords

  • ChIP-Seq
  • RNA-Seq
  • allele-specific
  • networks

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)
  • Applied Mathematics

Fingerprint Dive into the research topics of 'AlleleSeq: Analysis of allele-specific expression and binding in a network framework'. Together they form a unique fingerprint.

  • Cite this

    Rozowsky, J., Abyzov, A., Wang, J., Alves, P., Raha, D., Harmanci, A., Leng, J., Bjornson, R., Kong, Y., Kitabayashi, N., Bhardwaj, N., Rubin, M., Snyder, M., & Gerstein, M. (2011). AlleleSeq: Analysis of allele-specific expression and binding in a network framework. Molecular Systems Biology, 7, [522]. https://doi.org/10.1038/msb.2011.54