An efficient method for statistical significance calculation of transcription factor binding sites.

Various statistical models have been developed to describe the DNA binding preference of transcription factors, by which putative transcription factor binding sites (TFBS) can be identified according to scores assigned. Statistical significance of these scores, usually known as the p-value, play a critical role in identification. We developed an efficient algorithm to provide precise calculation of the statistical significance, remarkably enhancing the calculation efficiency by reducing the time complexity from an exponent scale to a linear scale, and successfully extended the application of this algorithm to a wide range of models, from the commonly used position weight matrix models to the complicated Bayesian Network models. Further, we calculated p-values of all transcription factor DNA binding sites recorded in the database, JASPAR, and based on these, we investigated some unseen properties of p-values as a whole, such as the p-value distribution of different models and the p-value variance according to changed scoring schemes. We hope that our algorithm and the result of computational experiments would offer an improved solution to the statistical significance of transcription factor binding sites. The software to implement our method can be downloaded from http://pcal.biosino.org/pCal.html.