Biomedical subjects

Theodore D Liakopoulos

Publications and source records attributed to Theodore D Liakopoulos.

5 recordsLinked to original sources

PubMed2005

Evaluation of methods for predicting the topology of beta-barrel outer membrane proteins and a consensus prediction method.

BACKGROUND: Prediction of the transmembrane strands and topology of beta-barrel outer membrane proteins is of interest in current bioinformatics research. Several methods have been applied so far for this task, utilizing different algorithmic techniques and a number of freely available predictors exist. The methods can be grossly divided to those based on Hidden Markov Models (HMMs), on Neural Networks (NNs) and on Support Vector Machines (SVMs). In this work, we compare the different available methods for topology prediction of beta-barrel outer membrane proteins. We evaluate their performance on a non-redundant dataset of 20 beta-barrel outer membrane proteins of gram-negative bacteria, with structures known at atomic resolution. Also, we describe, for the first time, an effective way to combine the individual predictors, at will, to a single consensus prediction method. RESULTS: We assess the statistical significance of the performance of each prediction scheme and conclude that Hidden Markov Model based methods, HMM-B2TMR, ProfTMB and PRED-TMBB, are currently the best predictors, according to either the per-residue accuracy, the segments overlap measure (SOV) or the total number of proteins with correctly predicted topologies in the test set. Furthermore, we show that the available predictors perform better when only transmembrane beta-barrel domains are used for prediction, rather than the precursor full-length sequences, even though the HMM-based predictors are not influenced significantly. The consensus prediction method performs significantly better than each individual available predictor, since it increases the accuracy up to 4% regarding SOV and up to 15% in correctly predicted topologies. CONCLUSIONS: The consensus prediction method described in this work, optimizes the predicted topology with a dynamic programming algorithm and is implemented in a web-based application freely available to non-commercial users at http://bioinformatics.biol.uoa.gr/ConBBPRED.

Algorithms↗

PubMed2004

PRED-TMBB: a web server for predicting the topology of beta-barrel outer membrane proteins.

The beta-barrel outer membrane proteins constitute one of the two known structural classes of membrane proteins. Whereas there are several different web-based predictors for alpha-helical membrane proteins, currently there is no freely available prediction method for beta-barrel membrane proteins, at least with an acceptable level of accuracy. We present here a web server (PRED-TMBB, http://bioinformatics.biol.uoa.gr/PRED-TMBB) which is capable of predicting the transmembrane strands and the topology of beta-barrel outer membrane proteins of Gram-negative bacteria. The method is based on a Hidden Markov Model, trained according to the Conditional Maximum Likelihood criterion. The model was retrained and the training set now includes 16 non-homologous outer membrane proteins with structures known at atomic resolution. The user may submit one sequence at a time and has the option of choosing between three different decoding methods. The server reports the predicted topology of a given protein, a score indicating the probability of the protein being an outer membrane beta-barrel protein, posterior probabilities for the transmembrane strand prediction and a graphical representation of the assumed position of the transmembrane strands with respect to the lipid bilayer.

Bacterial Outer Membrane Proteins↗

PubMed2004

TMRPres2D: high quality visual representation of transmembrane protein models.

The 'TransMembrane protein Re-Presentation in 2-Dimensions' (TMRPres2D) tool, automates the creation of uniform, two-dimensional, high analysis graphical images/models of alpha-helical or beta-barrel transmembrane proteins. Protein sequence data and structural information may be acquired from public protein knowledge bases, emanate from prediction algorithms, or even be defined by the user. Several important biological and physical sequence attributes can be embedded in the graphical representation.

Amino Acid Sequence↗

PubMed2004

A Hidden Markov Model method, capable of predicting and discriminating beta-barrel outer membrane proteins.

BACKGROUND: Integral membrane proteins constitute about 20-30% of all proteins in the fully sequenced genomes. They come in two structural classes, the alpha-helical and the beta-barrel membrane proteins, demonstrating different physicochemical characteristics, structure and localization. While transmembrane segment prediction for the alpha-helical integral membrane proteins appears to be an easy task nowadays, the same is much more difficult for the beta-barrel membrane proteins. We developed a method, based on a Hidden Markov Model, capable of predicting the transmembrane beta-strands of the outer membrane proteins of gram-negative bacteria, and discriminating those from water-soluble proteins in large datasets. The model is trained in a discriminative manner, aiming at maximizing the probability of correct predictions rather than the likelihood of the sequences. RESULTS: The training has been performed on a non-redundant database of 14 outer membrane proteins with structures known at atomic resolution; it has been tested with a jacknife procedure, yielding a per residue accuracy of 84.2% and a correlation coefficient of 0.72, whereas for the self-consistency test the per residue accuracy was 88.1% and the correlation coefficient 0.824. The total number of correctly predicted topologies is 10 out of 14 in the self-consistency test, and 9 out of 14 in the jacknife. Furthermore, the model is capable of discriminating outer membrane from water-soluble proteins in large-scale applications, with a success rate of 88.8% and 89.2% for the correct classification of outer membrane and water-soluble proteins respectively, the highest rates obtained in the literature. That test has been performed independently on a set of known outer membrane proteins with low sequence identity with each other and also with the proteins of the training set. CONCLUSION: Based on the above, we developed a strategy, that enabled us to screen the entire proteome of E. coli for outer membrane proteins. The results were satisfactory, thus the method presented here appears to be suitable for screening entire proteomes for the discovery of novel outer membrane proteins. A web interface available for non-commercial users is located at: http://bioinformatics.biol.uoa.gr/PRED-TMBB, and it is the only freely available HMM-based predictor for beta-barrel outer membrane protein topology.

Databases, Protein↗

PubMed2004

waveTM: wavelet-based transmembrane segment prediction.

waveTM is a web tool for the prediction of transmembrane segments in alpha-helical membrane proteins. Prediction is performed by a dynamic programming algorithm on wavelet-denoised 'hydropathy' signals. Users submit a protein sequence and receive interactively the results. Topology prediction can also be obtained in conjunction with the algorithm OrienTM. A web server that implements the waveTM algorithm is freely available at http://bioinformatics.biol.uoa.gr/waveTM.

Algorithms↗