Annotation-based inference of transporter function

Motivation: We present a method for inferring and constructing transport reactions for transporter proteins based primarily on the analysis of the names of individual proteins in the genome annotation of an organism. Transport reactions are declarative descriptions of transporter activities, and thus can be manipulated computationally, unlike free-text protein names. Once transporter activities are encoded as transport reactions, a number of computational analyses are possible including database queries by transporter activity; inclusion of transporters into an automatically generated metabolic-map diagram that can be painted with omics data to aid in their interpretation; detection of anomalies in the metabolic and transport networks, such as substrates that are transported into the cell but are not inputs to any metabolic reaction or pathway; and comparative analyses of the transport capabilities of different organisms. Results: On randomly selected organisms, the method achieves precision and recall rates of 0.93 and 0.90, respectively in identifying transporter proteins by name within the complete genome. The method obtains 67.5% accuracy in predicting complete transport reactions; if allowance is made for predictions that are overly general yet not incorrect, reaction prediction accuracy is 82.5%. Availability: The method is implemented as part of PathoLogic, the inference component of the Pathway Tools software. Pathway Tools is freely available to researchers at non-commercial institutions, including source code; a fee applies to commercial institutions.