T3E: a tool for characterising the epigenetic profile of transposable elements using ChIP-seq data

The epigenetic profiles of noncoding sequences in the human genome have been assessed by Chromatin Immunoprecipitation Sequencing (ChIP-seq) by large international efforts like ENCODE. However, such analyses have traditionally disregarded transposable elements (TEs) – which comprise about half of the human genome. The repetitive nature of TEs results in ambiguously mapping ChIP-seq reads, which makes the characterisation of the epigenetic profiles of TEs technically challenging. Furthermore, standard approaches to ChIP-seq enrichment analysis randomly permute the genomic location of the read mappings to build a background. We demonstrate that the background constructed using such approaches does not reflect experimental biases and can result in artifactual enrichment. To address these problems, we developed the Transposable Element Enrichment Estimator (T3E) tool. Specifically, T3E estimates the read mapping coverage of TE families/subfamilies at a single-nucleotide resolution by weighting the number of read mappings associated with a TE family/subfamily by the total number of loci to which the corresponding reads map in the genome. Additionally, T3E computes ChIP-seq enrichment relative to a background constructed based on the structure of ChIP-seq input control. We show that T3E is able to detect context-specific enrichments at TEs by examining several ChIP-seq datasets in human and mouse. T3E is a novel open-source tool for unveiling the functional properties of TEs (available for use at https://github.com/michelleapaz/T3E).