A computational pipeline for constructing a personal diploid genome and determining sites of allele-specific activity is developed. Using a regulatory network framework, allele-specific binding and expression are found to be significantly coordinated across the genome.
Software was developed for building a personal diploid genome sequence, and determining sites of allele-specific binding and expression (AlleleSeq).This computational pipeline was used to analyze variation data, and deeply sequenced RNA-Seq and ChIP-Seq datasets, for individual NA12878 from the 1000 Genomes Project.The interaction between allele-specific binding and allele-specific expression are investigated, revealing clear coordination.
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.