Database Commons

a catalog of worldwide biological databases

ELISA (http://romi.bu.edu/elisa/) is a database that was designed for flexibility in defining interesting queries about protein domain evolution. We have defined and included both the inherent characteristics of the domains such as structure and function and comparisons of these characteristics between domains. Thus, the database is useful in defining structural and functional links between related protein domains and by extension sequences that encode them. In this database we introduce and employ a novel method of functional annotation and comparison. For each protein domain we create a probabilistic functional annotation tree using GO. We have designed an algorithm that accurately compares these trees and thus provides a measure of "functional distance" between two protein domains. Along with functional annotation, we have also included structural comparison between protein domains and best sequence comparisons to all known genomes. The latter enables researchers to dynamically do searches for domains sharing similar phylogenetic profiles. This combination of data and tools enables the researcher to design complex queries to carry out research in the areas of protein domain evolution, structure prediction and functional annotation of novel sequences.

The problem of functional annotation based on homology modeling is primary to current bioinformatics research. Researchers have noted regularities in sequence, structure and even chromosome organization that allow valid functional cross-annotation. However, these methods provide a lot of false negatives due to limited specificity inherent in the system. We want to create an evolutionarily inspired organization of data that would approach the issue of structure-function correlation from a new, probabilistic perspective. Such organization has possible applications in phylogeny, modeling of functional evolution and structural determination. ELISA (Evolutionary Lineage Inferred from Structural Analysis, http://romi.bu.edu/elisa) is an online database that combines functional annotation with structure and sequence homology modeling to place proteins into sequence-structure-function "neighborhoods". The atomic unit of the database is a set of sequences and structural templates that those sequences encode. A graph that is built from the structural comparison of these templates is called PDUG (protein domain universe graph). We introduce a method of functional inference through a probabilistic calculation done on an arbitrary set of PDUG nodes. Further, all PDUG structures are mapped onto all fully sequenced proteomes allowing an easy interface for evolutionary analysis and research into comparative proteomics. ELISA is the first database with applicability to evolutionary structural genomics explicitly in mind.
AVAILABILITY: The database is available at http://romi.bu.edu/elisa.