slimfinder a probabilistic method for identifying over-represented, convergently evolved, short linear motifs in proteinsslimfinder识别常见的概率统计方法,收敛进化在短时间内线性图案蛋白质.pdfVIP

SLiMFinder: A Probabilistic Method for Identifying Over- Represented, Convergently Evolved, Short Linear Motifs in Proteins 1,2 1 1 Richard J. Edwards *, Norman E. Davey , Denis C. Shields 1 University College Dublin Complex and Adaptive Systems Laboratory, University College Dublin Conway Institute of Biomolecular and Biomedical Sciences, University College Dublin, Dublin, Ireland, 2 School of Biological Sciences, University of Southampton, Southampton, United Kingdom Background. Short linear motifs (SLiMs) in proteins are functional microdomains of fundamental importance in many biological systems. SLiMs typically consist of a 3 to 10 amino acid stretch of the primary protein sequence, of which as few as two sites may be important for activity, making identification of novel SLiMs extremely difficult. In particular, it can be very difficult to distinguish a randomly recurring ‘‘motif’’ from a truly over-represented one. Incorporating ambiguous amino acid positions and/or variable-length wildcard spacers between defined residues further complicates the matter. Methodology/ Principal Findings. In this paper we present two algorithms. SLiMBuild identifies convergently evolved, short motifs in a dataset of proteins. Motifs are built by combining dimers into longer patterns, retaining only those motifs occurring in a sufficient number of unrelated proteins. Motifs with fixed amino acid positions are identified and then combined to incorporate amino acid ambiguity and variable-length wildcard spacers. The algorithm is computationally efficient compared to alternatives, particularly when datasets include homologous proteins, and provides great flexibility in the nature of motifs returned. The SLiMChance algorithm estimates the probability of returned motifs arising by chance, correcting for