ANFIS-based Fuzzy Systems for Searching DNA-Protein Binding Sites

Abstract

Transcriptional regulation mainly controls how genes are expressed and how cells behave based on the transcription factor (TF) proteins that bind upstream of the transcription start sites (TSSs) of genes. These TF DNA binding sites (TFBSs) are usually short (5-15 base pairs) and degenerate (some positions can have multiple possible alternatives). Traditionally, computational methods scan DNA sequences using the position weight matrix (PWM) of a given TF, calculate binding scores for each K-mer against the PWM, and finally classify a K-mer as to whether it is a putative TFBS or a background sequence based on a cut-off threshold. The FSCAN system, which is proposed in this paper, employs machine learning techniques to build a learner model that is able to identify TFBSs in a set of bound sequences without the need for a cut-off threshold. Our proposed method utilizes fuzzy inference techniques along with a distribution-based filtering algorithm to predict the binding sites of a TF given its PWM model and phastCons scores for the input DNA sequences. Data imbalance reduction techniques are also used to ease the learning of the adaptive-neuro fuzzy inference system (ANFIS) algorithm. The proposed system is tested on 22 ChIP-chip sequence-sets from the Saccharomyces Cerevisiae genome. Our results show that FSCAN outperforms other approaches like MatInspector and MATCH and is quite robust. As more transcriptional data becomes available, our proposed framework encourages the use of fuzzy logic techniques in the prediction of TFBSs.