We next explored the potential impact of sequence variation on ENCODE functional elements. We examined allele-specific variation using results from the GM12878 cells that are derived from an individual (NA12878) sequenced in the 1000 Genomes project, along with her parents. Since ENCODE assays are predominantly sequence-based, the trio design allows each GM12878 dataset to be divided by the specific parental contributions at heterozygous sites, producing aggregate haplotypic signals from multiple genomic sites. We examined 193 ENCODE assays for allele-specific biases using 1,409,992 phased, heterozygous SNPs and 167,096 indels (Figure 8). Alignment biases towards alleles present in the reference genome sequence were avoided utilising a sequence specifically tailored to the variants and haplotypes present in NA12878 (a ‘personalised genome’)73. We found instances of preferential binding towards each parental allele. For example, comparison of the results from the POLR2A, H3K79me2, and H3K27me3 assays in the region of NACC2 (Figure 8A) shows a strong paternal bias for H3K79me2 and POL2RA and a strong maternal bias for H3K27me3, suggesting differential activity for the maternal and paternal alleles.
