RESUMEN
The ability to rapidly and reliably develop hypotheses on the function of newly discovered protein sequences requires systematic and comprehensive analysis. Such an analysis, embodied within the DS GeneAtlas pipeline, has been used to critically evaluate the severe acute respiratory syndrome (SARS) genome with the goal of identifying new potential targets for viral therapeutic intervention. This paper discusses several new functional hypotheses on the roles played by the constituent gene products of SARS, and will serve as an example of how such assignments can be developed or extended on other systems of interest.
Asunto(s)
Genoma Viral , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/genética , Proteínas Virales/química , Proteínas Virales/genética , Secuencia de Aminoácidos , Animales , Sitios de Unión , ADN Helicasas/química , ADN Helicasas/genética , ARN Polimerasas Dirigidas por ADN/química , ARN Polimerasas Dirigidas por ADN/genética , ARN Polimerasas Dirigidas por ADN/metabolismo , Humanos , Modelos Moleculares , Datos de Secuencia Molecular , Estructura Secundaria de Proteína , ARN Helicasas/química , ARN Helicasas/genética , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/química , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/enzimología , Alineación de Secuencia , Análisis de Secuencia de Proteína , Homología de Secuencia de Aminoácido , Porcinos , Transcripción GenéticaRESUMEN
To maximise the assignment of function of the proteins encoded by a genome and to aid the search for novel drug targets, there is an emerging need for sensitive methods of predicting protein function on a genome-wide basis. GeneAtlas is an automated, high-throughput pipeline for the prediction of protein structure and function using sequence similarity detection, homology modelling and fold recognition methods. GeneAtlas is described in detail here. To test GeneAtlas, a 'virtual' genome was used, a subset of PDB structures from the SCOP database, in which the functional relationships are known. GeneAtlas detects additional relationships by building 3D models in comparison with the sequence searching method PSI-BLAST. Functionally related proteins with sequence identity below the twilight zone can be recognised correctly.