AlleleSeq: analysis of allele-specific expression and binding in a network framework.
Molecular systems biology. 2011;7:522.
- 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.
- References
Related data
- File format
- VCF
- Data summary
- The 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 (for expression (ASE) and binding (ASB)) with significant differences in the number of mapped reads between maternal and paternal alleles. The initial sets of ASE and ASB calls from Rozowsky et al. are augmented by allele-specific call for all the available GM12878 RNA-Seq and ChIP-Seq data from the 2012 ENCODE rollout (see Djebali et al [PMID:22955620] for additional ASE SNPs and Gerstein et al. [PMID:22955619] for additional ASB SNPs).