Top-Down Crawl: a method for the ultra-rapid and motif-free alignment of sequences with associated binding metrics

• Published in: Bioinformatics (Oxford, England) Vol. 38; no. 22; pp. 5121 - 5123
• Main Authors: Cooper, Brendon H, Chiu, Tsu-Pei, Rohs, Remo
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 15.11.2022
• Subjects: Applications Note; Binding Sites; Position-Specific Scoring Matrices; Protein Binding; Sequence Analysis, DNA - methods; Software
• ISSN: 1367-4803; 1367-4811
• DOI: 10.1093/bioinformatics/btac653

Several high-throughput protein-DNA binding methods currently available produce highly reproducible measurements of binding affinity at the level of the k-mer. However, understanding where a k-mer is positioned along a binding site sequence depends on alignment. Here, we present Top-Down Crawl (TDC), an ultra-rapid tool designed for the alignment of k-mer level data in a rank-dependent and position weight matrix (PWM)-independent manner. As the framework only depends on the rank of the input, the method can accept input from many types of experiments (protein binding microarray, SELEX-seq, SMiLE-seq, etc.) without the need for specialized parameterization. Measuring the performance of the alignment using multiple linear regression with 5-fold cross-validation, we find TDC to perform as well as or better than computationally expensive PWM-based methods. TDC can be run online at https://topdowncrawl.usc.edu or locally as a python package available through pip at https://pypi.org/project/TopDownCrawl. Supplementary data are available at Bioinformatics online.