Recognition of multiple patterns in unaligned sets of sequences: Comparison of kernel clustering method with other methods

Abstract

Motivation: Transcription factor binding sites often differ significantly in their primary sequence and can hardly be aligned. Often one set of sites can contain several subsets of sequences that follow not just one but several different patterns. There is a need for sensitive methods to reveal multiple patterns in unaligned sets of sequences. Results: We developed a novel method for analysis of unaligned sets of sequences based on kernel estimation. The method is able to reveal 'multiple local patterns' - a set of weight matrices. Every weight matrix characterizes a pattern that can be found in a significant subset of sequences under analysis. The method developed has been compared with several other methods of pattern discovery such as Gibbs sampling, MEME, CONSENSUS, MULTIPROFILER and PROJECTION. The kernel method showed the best performance in terms of how close the revealed weight matrices are to the original ones. We applied the kernel method to analyze three samples of promoters (cell-cycle, T-cells and muscle-specific). We compared the multiple patterns revealed with the TRANSFAC library of weight matrices and found a strong similarity to several weight matrices for transcription factors known to be involved in the mentioned specific gene regulation. © Oxford University Press 2004; all rights reserved.