- Article -
| In Silico Biology 9, 0012 (2009); ©2009, Bioinformation Systems e.V. |
Prediction of polyadenylation signals in human DNA sequences using nucleotide frequencies
Firoz Ahmed, Manish Kumar and Gajendra P. S. Raghava*
Bioinformatics Centre, Institute of Microbial Technology, Sector 39-A, Chandigarh, India
* Corresponding author
Email: raghava@imtech.res.in
Edited by E. Wingender; received July 27, 2008; revised November 24, 2008, and April 13, 2009; accepted April 13, 2009; published May 23, 2009
Abstract
The polyadenylation signal plays a key role in determining the site for addition of a polyadenylated tail to nascent mRNA and its mutation(s) are reported in many diseases. Thus, identifying poly(A) sites is important for understanding the regulation and stability of mRNA. In this study, Support Vector Machine (SVM) models have been developed for predicting poly(A) signals in a DNA sequence using 100 nucleotides, each upstream and downstream of this signal. Here, we introduced a novel split nucleotide frequency technique, and the models thus developed achieved maximum Matthews correlation coefficients (MCC) of 0.58, 0.69, 0.70 and 0.69 using mononucleotide, dinucleotide, trinucleotide, and tetranucleotide frequencies, respectively. Finally, a hybrid model developed using a combination of dinucleotide, 2nd order dinucleotide and tetranucleotide frequencies, achieved a maximum MCC of 0.72. Moreover, for independent datasets this model achieved a precision ranging from 75.8 - 95.7% with a sensitivity of 57%, which is better than any other known methods.
Keywords: polyadenylation signals, mRNA, Support Vector Machine (SVM), Matthews correlation coefficient (MCC), ROC plot, nucleotide frequency