Variations on probabilistic suffix trees: Statistical modeling and prediction of protein families

Abstract

Motivation: We present a method for modeling protein families by means of probabilistic suffix trees (PSTs). The method is based on identifying significant patterns in a set of related protein sequences. The patterns can be of arbitrary length, and the input sequences do not need to be aligned, nor is delineation of domain boundaries required. The method is automatic, and can be applied, without assuming any preliminary biological information, with surprising success. Basic biological considerations such as amino acid background probabilities, and amino acids substitution probabilities can be incorporated to improve performance. Results: The PST can serve as a predictive tool for protein sequence classification, and for detecting conserved patterns (possibly functionally or structurally important) within protein sequences. The method was tested on the Pfam database of protein families with more than satisfactory performance. Exhaustive evaluations show that the PST model detects much more related sequences than pairwise methods such as Gapped-BLAST, and is almost as sensitive as a hidden Markov model that is trained from a multiple alignment of the input sequences, while being much faster.