Biomedical informatics and translational medicine

Biomedical informatics involves a core set of methodologies that can provide a foundation for crossing the "translational barriers" associated with translational medicine. To this end, the fundamental aspects of biomedical informatics (e.g., bioinformatics, imaging informatics, clinical informatics, and public health informatics) may be essential in helping improve the ability to bring basic research findings to the bedside, evaluate the efficacy of interventions across communities, and enable the assessment of the eventual impact of translational medicine innovations on health policies. Here, a brief description is provided for a selection of key biomedical informatics topics (Decision Support, Natural Language Processing, Standards, Information Retrieval, and Electronic Health Records) and their relevance to translational medicine. Based on contributions and advancements in each of these topic areas, the article proposes that biomedical informatics practitioners ("biomedical informaticians") can be essential members of translational medicine teams

Mimicking enzyme evolution by generating new (βα)(8)-barrels from (βα)(4)-half-barrels

Gene duplication and fusion events that multiply and link functional protein domains are crucial mechanisms of enzyme evolution. The analysis of amino acid sequences and three-dimensional structures suggested that the (βα)(8)-barrel, which is the most frequent fold among enzymes, has evolved by the duplication, fusion, and mixing of (βα)(4)-half-barrel domains. Here, we mimicked this evolutionary strategy by generating in vitro (βα)(8)-barrels from (βα)(4)-half-barrels that were deduced from the enzymes imidazole glycerol phosphate synthase (HisF) and N′[(5′-phosphoribosyl)formimino]-5-aminoimidazole-4-carboxamide-ribonucleotide isomerase (HisA). To this end, the gene for the C-terminal (βα)(4)-half-barrel (HisF-C) of HisF was duplicated and fused in tandem to yield HisF-CC, which is more stable than HisF-C. In the next step, by optimizing side-chain interactions within the center of the β-barrel of HisF-CC, the monomeric and compact (βα)(8)-barrel protein HisF-C*C was generated. Moreover, the genes for the N- and C-terminal (βα)(4)-half-barrels of HisF and HisA were fused crosswise to yield the chimeric proteins HisFA and HisAF. Whereas HisFA contains native secondary structure elements but adopts ill-defined association states, the (βα)(8)-barrel HisAF is a stable and compact monomer that reversibly unfolds with high cooperativity. The results obtained suggest a previously undescribed dimension for the diversification of enzymatic activities: new (βα)(8)-barrels with novel functions might have evolved by the exchange of (βα)(4)-half-barrel domains with distinct functional properties