• A large-scale evaluation of computational protein function prediction

      Radivojac, P; Clark, WT; Oron, TR; Schnoes, AM; Wittkop, T; Sokolov, A; Graim, K; Funk, C; Verspoor, K; Ben-Hur, A; Pandey, G; Yunes, JM; Talwalkar, AS; Repo, S; Souza, ML; Piovesan, D; Casadio, R; Wang, Z; Cheng, J; Fang, H; Gough, J; Koskinen, P; Törönen, P; Nokso-Koivisto, J; Holm, L; Cozzetto, D; Buchan, DWA; Bryson, K; Jones, DT; Limaye, B; Inamdar, H; Datta, A; Manjari, SK; Joshi, R; Chitale, M; Kihara, D; Lisewski, AM; Erdin, S; Venner, E; Lichtarge, O; Rentzsch, R; Yang, H; Romero, AE; Bhat, P; Paccanaro, A; Hamp, T; Kaßner, R; Seemayer, S; Vicedo, E; Schaefer, C; Achten, D; Auer, F; Boehm, A; Braun, T; Hecht, M; Heron, M; Hönigschmid, P; Hopf, TA; Kaufmann, S; Kiening, M; Krompass, D; Landerer, C; Mahlich, Y; Roos, M; Björne, J; Salakoski, T; Wong, A; Shatkay, H; Gatzmann, F; Sommer, I; Wass, MN; Sternberg, MJE; Škunca, N; Supek, F; Bošnjak, M; Panov, P; Džeroski, S; Šmuc, T; Kourmpetis, YAI; Van Dijk, ADJ; Ter Braak, CJF; Zhou, Y; Gong, Q; Dong, X; Tian, W; Falda, M; Fontana, P; Lavezzo, E; Di Camillo, B; Toppo, S; Lan, L; Djuric, N; Guo, Y; Vucetic, S; Bairoch, A; Linial, M; Babbitt, PC; Brenner, SE; Orengo, C; Rost, B (2013-03-01)
      Automated annotation of protein function is challenging. As the number of sequenced genomes rapidly grows, the overwhelming majority of protein products can only be annotated computationally. If computational predictions are to be relied upon, it is crucial that the accuracy of these methods be high. Here we report the results from the first large-scale community-based critical assessment of protein function annotation (CAFA) experiment. Fifty-four methods representing the state of the art for protein function prediction were evaluated on a target set of 866 proteins from 11 organisms. Two findings stand out: (i) today's best protein function prediction algorithms substantially outperform widely used first-generation methods, with large gains on all types of targets; and (ii) although the top methods perform well enough to guide experiments, there is considerable need for improvement of currently available tools. © 2013 Nature America, Inc. All rights reserved.
    • Length-dependent prediction of protein in intrinsic disorder

      Peng, K; Radivojac, P; Vucetic, S; Dunker, AK; Obradovic, Z (2006-04-17)
      Background: Due to the functional importance of intrinsically disordered proteins or protein regions, prediction of intrinsic protein disorder from amino acid sequence has become an area of active research as witnessed in the 6th experiment on Critical Assessment of Techniques for Protein Structure Prediction (CASP6). Since the initial work by Romero et al. (Identifying disordered regions in proteins from amino acid sequences, IEEE Int. Conf. Neural Netw., 1997), our group has developed several predictors optimized for long disordered regions (>30 residues) with prediction accuracy exceeding 85%. However, these predictors are less successful on short disordered regions (≤30 residues). A probable cause is a length-dependent amino acid compositions and sequence properties of disordered regions. Results: We proposed two new predictor models, VSL2-M1 and VSL2-M2, to address this length-dependency problem in prediction of intrinsic protein disorder. These two predictors are similar to the original VSL1 predictor used in the CASP6 experiment. In both models, two specialized predictors were first built and optimized for short (≤30 residues) and long disordered regions (>30 residues), respectively. A meta predictor was then trained to integrate the specialized predictors into the final predictor model. As the 10-fold cross-validation results showed, the VSL2 predictors achieved well-balanced prediction accuracies of 81% on both short and long disordered regions. Comparisons over the VSL2 training dataset via 10-fold cross-validation and a blind-test set of unrelated recent PDB chains indicated that VSL2 predictors were significantly more accurate than several existing predictors of intrinsic protein disorder. Conclusion: The VSL2 predictors are applicable to disordered regions of any length and can accurately identify the short disordered regions that are often misclassified by our previous disorder predictors. The success of the VSL2 predictors further confirmed the previously observed differences in amino acid compositions and sequence properties between short and long disordered regions, and justified our approaches for modelling short and long disordered regions separately. The VSL2 predictors are freely accessible for non-commercial use at http://www.ist.temple.edu/disprot/predictorVSL2.php. © 2006 Peng et al; licensee BioMed Central Ltd.