To further study the potential effects of NA12878 genome variants on TF binding regions, we performed peak-calling using a constructed personal diploid genome sequence for NA1287873. We aligned ChIP-seq sequences from GM12878 separately against the maternal and paternal haplotypes. As expected, a greater fraction of reads were aligned than to the reference genome (see Supplementary Information, Supplementary Figure K1). On average, approximately 1% of TF-binding sites in GM12878 are detected in a haplotype-specific fashion. For instance, Figure 9B shows a CTCF-binding site not detected using the reference sequence that is only present on the paternal haplotype due to a 1-bp deletion (see also Supplementary Figure K2). As costs of DNA sequencing decrease further, optimized analysis of ENCODE-type data should use the genome sequence of the individual or cell being analyzed when possible.
