Unveiling epigenetic profiles of transposable elements in ChIP-seq data using T3E

Transposable elements (TEs) comprise almost half of the human genome and the study of their epigenetic profiles has become a hot topic. Chromatin Immunoprecipitation Sequencing (ChIP-seq) technologies have helped reveal the cis-regulatory roles of TEs.
However, several technical challenges are faced. The most prominent difficulty concerns the ambiguous mapping of reads derived from TEs, especially those that were recently proliferating. Another difficulty is the definition of an appropriate background for enrichment analysis. The standard approach randomly permutes the location of the read mappings in the genome, assuming a uniform distribution that does not reflect biases in library preparation or TE insertion patterns, and often leads to false positive or negative TE enrichments. To tackle these issues we developed the Transposable Element Enrichment Estimator (T3E), a framework for the functional analysis of TEs. T3E compares the epigenetic profiles of TE families/subfamilies to a background profile constructed based on the structure of the ChIP-seq control experiment. Another innovation of T3E is how it estimates the coverage of TE families/subfamilies. Specifically, acknowledging the ambiguity of the data, T3E weights the number of reads mapping to a TE family/subfamily copy by the overall number of loci to which the reads map in the genome, and this is done at single-nucleotide resolution. We applied T3E to confirm or refute previous results, and we found evidence supporting the implication of TEs in important cellular processes.