We present the Database of Disordered Protein Prediction (D²P²), available at http://d2p2.pro (including website source code). A battery of disorder predictors and their variants, VL-XT, VSL2b, PrDOS, PV2, Espritz and IUPred, were run on all protein sequences from 1765 complete proteomes (to be updated as more genomes are completed). Integrated with these results are all of the predicted (mostly structured) SCOP domains using the SUPERFAMILY predictor. These disorder/structure annotations together enable comparison of the disorder predictors with each other and examination of the overlap between disordered predictions and SCOP domains on a large scale. D²P² will increase our understanding of the interplay between disorder and structure, the genomic distribution of disorder, and its evolutionary history. The parsed data are made available in a unified format for download as flat files or SQL tables either by genome, by predictor, or for the complete set. An interactive website provides a graphical view of each protein annotated with the SCOP domains and disordered regions from all predictors overlaid (or shown as a consensus). There are statistics and tools for browsing and comparing genomes and their disorder within the context of their position on the tree of life.

Motivation: Molecular recognition features (MoRFs) are short binding regions located within longer intrinsically disordered regions that bind to protein partners via disorder-to-order transitions. MoRFs are implicated in important processes including signaling and regulation. However, only a limited number of experimentally validated MoRFs is known, which motivates development of computational methods that predict MoRFs from protein chains. Results: We introduce a new MoRF predictor, MoRFpred, which identifies all MoRF types (α, β, coil and complex). We develop a comprehensive dataset of annotated MoRFs to build and empirically compare our method. MoRFpred utilizes a novel design in which annotations generated by sequence alignment are fused with predictions generated by a Support Vector Machine (SVM), which uses a custom designed set of sequence-derived features. The features provide information about evolutionary profiles, selected physiochemical properties of amino acids, and predicted disorder, solvent accessibility and B-factors. Empirical evaluation on several datasets shows that MoRFpred outperforms related methods: α-MoRF-Pred that predicts α-MoRFs and ANCHOR which finds disordered regions that become ordered when bound to a globular partner. We show that our predicted (new) MoRF regions have non-random sequence similarity with native MoRFs. We use this observation along with the fact that predictions with higher probability are more accurate to identify putative MoRF regions. We also identify a few sequence-derived hallmarks of MoRFs. They are characterized by dips in the disorder predictions and higher hydrophobicity and stability when compared to adjacent (in the chain) residues. Availability:http://biomine.ece.ualberta.ca/MoRFpred/; http://biomine.ece.ualberta.ca/MoRFpred/Supplement.pdf Contact:lkurgan@ece.ualberta.ca Supplementary information: Supplementary data are available at Bioinformatics online.

The task of extracting knowledge from databases is quite often performed by machine learning algorithms. The majority of these algorithms can be applied only to data described by discrete numerical or nominal attributes (features). In the case of continuous attributes, there is a need for a discretization algorithm that transforms continuous attributes into discrete ones. We describe such an algorithm, called CAIM (class-attribute interdependence maximization), which is designed to work with supervised data. The goal of the CAIM algorithm is to maximize the class-attribute interdependence and to generate a (possibly) minimal number of discrete intervals. The algorithm does not require the user to predefine the number of intervals, as opposed to some other discretization algorithms. The tests performed using CAIM and six other state-of-the-art discretization algorithms show that discrete attributes generated by the CAIM algorithm almost always have the lowest number of intervals and the highest class-attribute interdependency. Two machine learning algorithms, the CLIP4 rule algorithm and the decision tree algorithm, are used to generate classification rules from data discretized by CAIM. For both the CLIP4 and decision tree algorithms, the accuracy of the generated rules is higher and the number of the rules is lower for data discretized using the CAIM algorithm when compared to data discretized using six other discretization algorithms. The highest classification accuracy was achieved for data sets discretized with the CAIM algorithm, as compared with the other six algorithms.