The literature on protein function prediction is currently dominated by works aimed at maximizing predictive accuracy, ignoring the important issues of validation and interpretation of discovered knowledge, which can lead to new insights and hypotheses that are biologically meaningful and advance the understanding of protein functions by biologists. The overall goal of this paper is to critically evaluate this approach, offering a refreshing new perspective on this issue, focusing not only on predictive accuracy but also on the comprehensibility of the induced protein function prediction models. More specifically, this paper aims to offer two main contributions to the area of protein function prediction. First, it presents the case for discovering comprehensible protein function prediction models from data, discussing in detail the advantages of such models, namely, increasing the confidence of the biologist in the system's predictions, leading to new insights about the data and the formulation of new biological hypotheses, and detecting errors in the data. Second, it presents a critical review of the pros and cons of several different knowledge representations that can be used in order to support the discovery of comprehensible protein function prediction models.

Programmatic access to the UniProt Knowledgebase (UniProtKB) is essential for many bioinformatics applications dealing with protein data. We have created a Java library named UniProtJAPI, which facilitates the integration of UniProt data into Java-based software applications. The library supports queries and similarity searches that return UniProtKB entries in the form of Java objects. These objects contain functional annotations or sequence information associated with a UniProt entry. Here, we briefly describe the UniProtJAPI and demonstrate its usage.

In this study, we present two freely available and complementary Distributed Annotation System (DAS) resources: a DAS reference server that provides up-to-date sequence and annotation from UniProt, with additional feature links and database cross-references from InterPro and a DAS client implemented using Java and Macromedia Flash that is optimized for the display of protein features.

SUMMARY: The CluSTr database employs a fully automatic single-linkage hierarchical clustering method based on a similarity matrix. In order to compute the matrix, first all-against-all pair-wise comparisons between protein sequences are computed using the Smith-Waterman algorithm. The statistical significance of the similarity scores is then assessed using a Monte Carlo analysis, yielding Z-values, which are used to populate the matrix. This paper describes automated annotation experiments that quantify the predictive power and hence the biological relevance of the CluSTr data. The experiments utilized the UniProt data-mining framework to derive annotation predictions using combinations of InterPro and CluSTr. We show that this combination of data sources greatly increases the precision of predictions made by the data-mining framework, compared with the use of InterPro data alone. We conclude that the CluSTr approach to clustering proteins makes a valuable contribution to traditional protein classifications. AVAILABILITY: http://www.ebi.ac.uk/clustr/.