pubmed.ncbi.nlm.nih.gov

Improved sequence-based prediction of disordered regions with multilayer fusion of multiple information sources - PubMed

  • ️Fri Jan 01 2010

Comparative Study

Improved sequence-based prediction of disordered regions with multilayer fusion of multiple information sources

Marcin J Mizianty et al. Bioinformatics. 2010.

Abstract

Motivation: Intrinsically disordered proteins play a crucial role in numerous regulatory processes. Their abundance and ubiquity combined with a relatively low quantity of their annotations motivate research toward the development of computational models that predict disordered regions from protein sequences. Although the prediction quality of these methods continues to rise, novel and improved predictors are urgently needed.

Results: We propose a novel method, named MFDp (Multilayered Fusion-based Disorder predictor), that aims to improve over the current disorder predictors. MFDp is as an ensemble of 3 Support Vector Machines specialized for the prediction of short, long and generic disordered regions. It combines three complementary disorder predictors, sequence, sequence profiles, predicted secondary structure, solvent accessibility, backbone dihedral torsion angles, residue flexibility and B-factors. Our method utilizes a custom-designed set of features that are based on raw predictions and aggregated raw values and recognizes various types of disorder. The MFDp is compared at the residue level on two datasets against eight recent disorder predictors and top-performing methods from the most recent CASP8 experiment. In spite of using training chains with <or=25% similarity to the test sequences, our method consistently and significantly outperforms the other methods based on the MCC index. The MFDp outperforms modern disorder predictors for the binary disorder assignment and provides competitive real-valued predictions. The MFDp's outputs are also shown to outperform the other methods in the identification of proteins with long disordered regions.

Availability: http://biomine.ece.ualberta.ca/MFDp.html.

PubMed Disclaimer

Figures

Fig. 1.
Fig. 1.

Architecture of the MFDp method.

Fig. 2.
Fig. 2.

ROCs for the predictions on the (A) MxD and (B) CASP8 datasets.

Fig. 3.
Fig. 3.

ROCs for the predictions of proteins with long-disordered segments on the MxD dataset.

Fig. 4.
Fig. 4.

Comparison of predictions from MFDp, DISOPRED2 (DP2), IUPREDL (IUPL), IUPREDS (IUPS) and DISOclust (DISOc), MD; and two CASP8 predictors with the highest MCC, McGuffin (379) and GeneSilicoMetaServer (297) for CASP8 targets T0480 (on the left) and T0404 (on the right). The ‘–’ and ‘D’ denote the ordered and disordered residues, respectively. The actual disorder annotations are shown in the first line.

Similar articles

Cited by

References

    1. Altschul SF, et al. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 1997;25:3389–3402. - PMC - PubMed
    1. Berman HM, et al. The Protein Data Bank. Nucleic Acids Res. 2000;28:235–242. - PMC - PubMed
    1. Bordoli L, et al. Assessment of disorder predictions in CASP7. Proteins. 2007;69(Suppl. 8):129–136. - PubMed
    1. Cheng J, et al. Accurate prediction of protein disordered regions by mining protein structure data. Data Mining Knowl. Disc. 2005;11:213–222.
    1. Dosztányi Z, et al. IUPred: web server for the prediction of intrinsically unstructured regions of proteins based on estimated energy content. Bioinformatics. 2005;21:3433–3434. - PubMed

Publication types

MeSH terms

Substances