Mapping personal functional data to personal genomes

Abstract

Motivation: The sequencing of personal genomes enabled analysis of variation in transcription factor (TF) binding, chromatin structure and gene expression and indicated how they contribute to phenotypic variation. It is hypothesized that using the reference genome for mapping ChIP-seq or RNA-seq reads may introduce errors, especially at polymorphic genomic regions.

Results: We developed a Personal Genome Editor (perEditor) that changes the reference human genome (NCBI36/hg18) into an individual genome, taking into account single nucleotide polymorphisms (SNPs), insertions and deletions, copy number variation, and chromosomal rearrangements. perEditor outputs two alleles (maternal, paternal) of the individual genome that is ready for mapping ChIP-seq and RNA-seq reads, and enabling the analyses of allele specific binding, chromatin structure and gene expression.

Availability: perEditor is available at http://biocomp.bioen.uiuc.edu/perEditor.

Contact: szhong@illinois.edu.

Fig. 1.

Relative difference of ChIP-seq reads alignable to individual genome and reference genome. Such relative differences were designed to approximate the differences of estimated binding intensities. For each 200 bp window on the genome, the number of alignable reads to the individual genome (α) was compared to that aligned to the reference genome (β), by taking the relative difference |α−β|/max(α,β). The distribution of the windows with 10 or more reads (max(α,β)≥10) with respect to their relative differences is drawn as a histogram. m, maternal allele. Red bars: α>β, blue bars: α<β.

Fig. 2.

An example of the genome differences and the allele differences. The NFκB ChIP-seq reads were mapped to the two alleles of the GM10847 genome (green and red tracks), as well as to the human reference genome (hg18, orange track). The height of colored bars represents the number of overlapping ChIP-seq reads on that genomic location. A strong peak was observed (19 overlapping ChIP-seq reads) in the second promoter of the TBX5 gene on the paternal allele of GM10847, overlapping with two of her heterozygous SNPs. This peak does not show up in her maternal allele or in the reference genome.