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PRED-TMBB2: improved topology prediction and detection of beta-barrel outer membrane proteins
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab). University of Thessaly, Greece .
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
Number of Authors: 3
2016 (English)In: Bioinformatics, ISSN 1367-4803, E-ISSN 1367-4811, Vol. 32, no 17, 665-671 p.Article in journal (Refereed) Published
Abstract [en]

Motivation: The PRED-TMBB method is based on Hidden Markov Models and is capable of predicting the topology of beta-barrel outer membrane proteins and discriminate them from water-soluble ones. Here, we present an updated version of the method, PRED-TMBB2, with several newly developed features that improve its performance. The inclusion of a properly defined end state allows for better modeling of the beta-barrel domain, while different emission probabilities for the adjacent residues in strands are used to incorporate knowledge concerning the asymmetric amino acid distribution occurring there. Furthermore, the training was performed using newly developed algorithms in order to optimize the labels of the training sequences. Moreover, the method is retrained on a larger, non-redundant dataset which includes recently solved structures, and a newly developed decoding method was added to the already available options. Finally, the method now allows the incorporation of evolutionary information in the form of multiple sequence alignments. Results: The results of a strict cross-validation procedure show that PRED-TMBB2 with homology information performs significantly better compared to other available prediction methods. It yields 76% in correct topology predictions and outperforms the best available predictor by 7%, with an overall SOV of 0.9. Regarding detection of beta-barrel proteins, PRED-TMBB2, using just the query sequence as input, achieves an MCC value of 0.92, outperforming even predictors designed for this task and are much slower.

Place, publisher, year, edition, pages
2016. Vol. 32, no 17, 665-671 p.
National Category
Biological Sciences Bioinformatics (Computational Biology)
Research subject
Biochemistry towards Bioinformatics
URN: urn:nbn:se:su:diva-135026DOI: 10.1093/bioinformatics/btw444ISI: 000384666800034PubMedID: 27587687OAI: diva2:1045649
15th European Conference on Computational Biology (ECCB), The Hague, Netherlands, September 3-7, 2016
Available from: 2016-11-10 Created: 2016-10-31 Last updated: 2017-01-20Bibliographically approved
In thesis
1. Bioinformatics Methods for Topology Prediction of Membrane Proteins
Open this publication in new window or tab >>Bioinformatics Methods for Topology Prediction of Membrane Proteins
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Membrane proteins are key elements of the cell since they are associated with a variety of very important biological functions crucial to its survival. They are implicated in cellular recognition and adhesion, act as molecular receptors, transport substrates through membranes and exhibit specific enzymatic activity.This thesis is focused on integral membrane proteins, most of which contain transmembrane segments that form an alpha helix and are composed of mainly hydrophobic residues, spanning the lipid bilayer. A more specialized and less well-studied case, is the case of integral membrane proteins found in the outer membrane of Gram-negative bacteria and (presumably) in the outer envelope of mitochondria and chloroplasts, proteins whose transmembrane segments are formed by amphipathic beta strands that create a closed barrel (beta-barrels). The importance of transmembrane proteins, as well as the inherent difficulties in crystallizing and obtaining three-dimensional structures of these, dictates the need for developing computational algorithms and tools that will allow for a reliable and fast prediction of their structural and functional features. In order to elucidate their function, we must acquire knowledge about their structure and topology with relation to the membrane. Therefore, a large number of computational methods have been developed in order to predict the transmembrane segments and the overall topology of transmembrane proteins. In this thesis, I initially describe a large-scale benchmark of many topology prediction tools in order to devise a strategy that will allow for better detection of alpha-helical membrane proteins in a proteome. Then, I give a description of construction of improved machine-learning algorithms and computer software for accurate topology prediction of transmembrane proteins and discrimination of such proteins from non-transmembrane proteins. Finally, I introduce a fast way to obtain a position-specific scoring matrix, which is essential for modern topology prediction methods.

Place, publisher, year, edition, pages
Stockholm: Department of Biochemistry and Biophysics, Stockholm University, 2017. 60 p.
National Category
Bioinformatics and Systems Biology
Research subject
Biochemistry towards Bioinformatics
urn:nbn:se:su:diva-138479 (URN)978-91-7649-648-0 (ISBN)978-91-7649-649-7 (ISBN)
Public defence
2017-02-23, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, 10:00 (English)

At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 3: Manuscript.

Available from: 2017-01-31 Created: 2017-01-23 Last updated: 2017-02-21Bibliographically approved

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Tsirigos, Konstantinos D.Elofsson, Arne
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