Interpretive proteomics—finding biological meaning in genome and proteome databases

摘要

The paleonlological, geological, and molecular records of life on Earth can be joined to obtain a comprehensive model for the proteins that are found throughout the life on the planet (Benner et al., 2002). Individual models for ca. 100,000 nuelear familics of protein sequences have hcen collected in the MASTERCATALOG. a commercial naturally organized database developed in collaboration with EraGen Biosciences (Madison. WI). The MASTERCATALOG facilitates interpretive proteomics by proiding the userwith high quality, pre-computed, second generation models for the evolutionary history of all of the protein families in the known biosphere. These models are advanced over those offered by first generation evolutionary databases (such as those presentedby Pfam. TIGRfam, and Hovergen) in several ways, including its focus on nuclear families, extensive identification of modules that undergo independent evolution, and the use throughout of explicitly reconstructed sequences from ancestral proteins that were present in now-extinct species. This second generation database is combined with a set of powerful interpretive proteomics tools that make up the FIREBIRD (Functional Inference from Reconstructed Evolutionary Biology) strategy for moving from genomesto biology. The FIREBIRD suite of tools offers a powerful framework for analyzing function in proteins, identifying targets of biomedical interest, and guiding pre-clinical drug development in animal models, inter alia. When applied to whole genomes, the suite identifies metabolic pathways and regulatory networks, permits the correlation of the life history of a lineage with its historical past, and captures interconnections that will move the biomedical researcher and biological chemist from the genome to organismic biology, ecosystems, and the planet.