Prediction of gene transcription start sites and initiation patterns from DNA sequence content

Graduation date: 2015The computational identification of gene Transcription Start Sites (TSSs) can provide insights into the regulation and function of genes without performing expensive experiments, particularly in organisms with incomplete annotations. High-resolution general-purpose TSS prediction remains a challenging problem, with little recent progress on the identification and differentiation of TSSs which are arranged in different spatial patterns along the chromosome.\ud \ud In this work, we present TIPR, a sequence-based machine learning model which identifies TSSs with high accuracy and resolution for multiple spatial distribution patterns along the genome, including broadly distributed TSS patterns which have previously been difficult to characterize. TIPR predicts not only the locations of TSSs, but also the expected spatial initiation pattern each TSS will form along the chromosome--a novel capability for TSS prediction algorithms. As spatial initiation patterns are associated with spatiotemporal expression patterns and gene function, this capability has the potential to improve gene annotations and our understanding of the regulation of transcription initiation. The high nucleotide-resolution of this model locates TSSs within 10 nucleotides or less on average