Evolving Models of Biological Sequence Similarity

For computer scientists the problem of biological data retrieval has become synonymous with homology-based retrieval of primary gene sequence data and their associated protein products. This perspective is accessible to computer scientists, as primary sequence data is modeled as strings and fundamental algorithmic tools can be applied. However, by sticking with this formative foundation, we computer scientists are failing to recognize new challenges and opportunities arising in this rapidly changing arena. Most notably, sequence data represents a polymer; a complex molecule is itself composed of a linear sequence of smaller molecules (monomers). The monomers interact with each other, both with their local neighbors and at long range, forming secondary and tertiary structure. As more sophisticated similarity models incorporate elements of these three-dimensional chemical environments, they have the potential to supplant the use of primary structure homology as the foremost method of data retrieval.