Pedersen, Bjørn Panella3; Ifrim, Georgiana4; Liboriussen, Poul3; Axelsen, Kristian B3; Palmgren, Michael Broberg5; Nissen, Poul3; Wiuf, Carsten Henrik6; Pedersen, Christian N S3
1 Section for Transport Biology, Department of Plant and Environmental Sciences, Faculty of Science, Københavns Universitet2 Department of Mathematical Sciences, Faculty of Science, Københavns Universitet3 Centre for Membrane Pumps in Cells and Disease-PUMPKin4 University College Dublin5 Section for Transport Biology, Department of Plant and Environmental Sciences, Faculty of Science, Københavns Universitet6 Department of Mathematical Sciences, Faculty of Science, Københavns Universitet
Abstract Background Structured Logistic Regression (SLR) is a newly developed machine learning tool first proposed in the context of text categorization. Current availability of extensive protein sequence databases calls for an automated method to reliably classify sequences and SLR seems well-suited for this task. The classification of P-type ATPases, a large family of ATP-driven membrane pumps transporting essential cations, was selected as a test-case that would generate important biological information as well as provide a proof-of-concept for the application of SLR to a large scale bioinformatics problem. Results Using SLR, we have built classifiers to identify and automatically categorize P-type ATPases into one of 11 pre-defined classes. The SLR-classifiers are compared to a Hidden Markov Model approach and shown to be highly accurate and scalable. Representing the bulk of currently known sequences, we analysed 9.3 million sequences in the UniProtKB and attempted to classify a large number of P-type ATPases. To examine the distribution of pumps on organisms, we also applied SLR to 1,123 complete genomes from the Entrez genome database. Finally, we analysed the predicted membrane topology of the identified P-type ATPases. Conclusions Using the SLR-based classification tool we are able to run a large scale study of P-type ATPases. This study provides proof-of-concept for the application of SLR to a bioinformatics problem and the analysis of P-type ATPases pinpoints new and interesting targets for further biochemical characterization and structural analysis.