Aligning and Clustering Patterns to Reveal the Protein Functionality of Sequences

Discovering sequence patterns with variations unveils significant functions of a protein family. Existing combinatorial methods of discovering patterns with variations are computationally expensive, and probabilistic methods require more elaborate probabilistic representation of the amino acid associations. To overcome these shortcomings, this paper presents a new computationally efficient method for representing patterns with variations in a compact representation called Aligned Pattern Cluster (AP Cluster). To tackle the runtime, our method discovers a shortened list of non-redundant statistically significant sequence associations based on our previous work. To address the representation of protein functional regions, our pattern alignment and clustering step, presented in this paper captures the conservations and variations of the aligned patterns. We further refine our solution to allow more coverage of sequences via extending the AP Clusters containing only statistically significant patterns to Weak and Conserved AP Clusters. When applied to the cytochrome c, the ubiquitin, and the triosephosphate isomerase protein families, our algorithm identifies the binding segments as well as the binding residues. When compared to other methods, ours discovers all binding sites in the AP Clusters with superior entropy and coverage. The identification of patterns with variations help biologists to avoid time-consuming simulations and experimentations. (Software available upon request).