Automatic annotation of protein function.

The annotation of protein function at genomic scale is essential for day-to-day work in biology and for any systematic approach to the modeling of biological systems. Currently, functional annotation is essentially based on the expansion of the relatively small number of experimentally determined functions to large collections of proteins. The task of systematic annotation faces formidable practical problems related to the accuracy of the input experimental information, the reliability of current systems for transferring information between related sequences, and the reproducibility of the links between database information and the original experiments reported in publications. These technical difficulties merely lie on the surface of the deeper problem of the evolution of protein function in the context of protein sequences and structures. Given the mixture of technical and scientific challenges, it is not surprising that errors are introduced, and expanded, in database annotations. In this situation, a more realistic option is the development of a reliability index for database annotations, instead of depending exclusively on efforts to correct databases. Several groups have attempted to compare the database annotations of similar proteins, which constitutes the first steps toward the calibration of the relationship between sequence and annotation space.