Motto: Representing Motifs in Consensus Sequences with Minimum Information Loss

• Published in: Genetics (Austin) Vol. 216; no. 2; pp. 353 - 358
• Main Authors: Wang, Mengchi, Wang, David, Zhang, Kai, Ngo, Vu, Fan, Shicai, Wang, Wei
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.10.2020; Genetics Society of America
• Subjects: Algorithms; Amino acids; Binding sites; Conserved sequence; Divergence; DNA methylation; Genetics; Genome, Human; Genomes; Humans; Information theory; Investigations; Logos; Mathematical analysis; Matrix methods; Methods; Nucleotide sequence; Nucleotides; Position-Specific Scoring Matrices; Representations; Sequence analysis; Sequence Analysis, DNA - methods; Sequence Analysis, DNA - standards; Sequences; Transcription factors; Transcription Factors - genetics; Weight; consensus; transcription factor binding; information theory; motif; sequence logo
• ISSN: 1943-2631; 0016-6731; 1943-2631
• DOI: 10.1534/genetics.120.303597

Abstract Sequence analysis frequently requires intuitive understanding and convenient representation of motifs. Typically, motifs are represented as position weight matrices (PWMs) and visualized using sequence logos. However, in many scenarios, in order to interpret the motif information or search for motif matches, it is compact and sufficient to represent motifs by wildcard-style consensus sequences (such as [GC][AT]GATAAG[GAC]). Based on mutual information theory and Jensen-Shannon divergence, we propose a mathematical framework to minimize the information loss in converting PWMs to consensus sequences. We name this representation as sequence Motto and have implemented an efficient algorithm with flexible options for converting motif PWMs into Motto from nucleotides, amino acids, and customized characters. We show that this representation provides a simple and efficient way to identify the binding sites of 1156 common transcription factors (TFs) in the human genome. The effectiveness of the method was benchmarked by comparing sequence matches found by Motto with PWM scanning results found by FIMO. On average, our method achieves a 0.81 area under the precision-recall curve, significantly (P-value < 0.01) outperforming all existing methods, including maximal positional weight, Cavener’s method, and minimal mean square error. We believe this representation provides a distilled summary of a motif, as well as the statistical justification.