Computational modeling of oligonucleotide positional densities for human promoter prediction

Abstract

Objective: The gene promoter region controls transcriptional initiation of a gene, which is the most important step in gene regulation. In-silico detection of promoter region in genomic sequences has a number of applications in gene discovery and understanding gene expression regulation. However, computational prediction of eukaryotic poly-II promoters has remained a difficult task. This paper introduces a novel statistical technique for detecting promoter regions in long genomic sequences. Method: A number of existing techniques analyze the occurrence frequencies of oligonucleotides in promoter sequences as compared to other genomic regions. In contrast, the present work studies the positional densities of oligonucleotides in promoter sequences. The analysis does not require any non-promoter sequence dataset or any model of the background oligonucleotide content of the genome. The statistical model learnt from a dataset of promoter sequences automatically recognizes a number of transcription factor binding sites simultaneously with their occurrence positions relative to the transcription start site. Based on this model, a continuous naïve Bayes classifier is developed for the detection of human promoters and transcription start sites in genomic sequences. Results: The present study extends the scope of statistical models in general promoter modeling and prediction. Promoter sequence features learnt by the model correlate well with known biological facts. Results of human transcription start site prediction compare favorably with existing 2nd generation promoter prediction tools. © 2005 Elsevier B.V. All rights reserved.