Connect the dots: exposing hidden protein family connections from the entire sequence tree

Motivation: Mapping of remote evolutionary links is a classic computational problem of much interest. Relating protein families allows for functional and structural inference on uncharacterized families. Since sequences have diverged beyond reliable alignment, these are too remote to identify by conventional methods. Approach: We present a method to systematically identify remote evolutionary relations between protein families, leveraging a novel evolutionary tree of all protein sequences and families. The tree is able to trace very faint links, owing to the robustness of considering the entire volume of pairwise sequence similarities at construction. Our method systematically scans the tree for clusters which partition exceptionally well into extant protein families, thus suggesting an evolutionary breakpoint in a putative ancient superfamily. Our method does not require family profiles (or HMMs), or multiple alignment. Results: Considering the entire Pfam database, we are able to su...

• Type: Conference
• Year: 2008
• Where: ECCB
• Authors: Yaniv Loewenstein, Michal Linial
• Keywords: Biology, ECCB 2008, Extant Protein Families, Protein Families, Remote Evolutionary Links