Large scale identification and categorization of protein sequences using structured logistic regression.
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.
Centre for Membrane Pumps in Cells and Disease - PUMPKIN, Danish National Research Foundation, Aarhus C, Denmark ; Department of Molecular Biology, Aarhus University, Aarhus C, Denmark.
Bjørn P
BP
Pedersen
INSIGHT Centre for Data Analytics, University College Dublin, Dublin, Ireland.
Georgiana
G
Ifrim
Centre for Membrane Pumps in Cells and Disease - PUMPKIN, Danish National Research Foundation, Aarhus C, Denmark ; Bioinformatics Research Centre, Aarhus University, Aarhus C, Denmark.
Poul
P
Liboriussen
Centre for Membrane Pumps in Cells and Disease - PUMPKIN, Danish National Research Foundation, Aarhus C, Denmark ; Swiss-Prot Group, Swiss Institute of Bioinformatics, CMU, Geneva, Switzerland.
Kristian B
KB
Axelsen
Centre for Membrane Pumps in Cells and Disease - PUMPKIN, Danish National Research Foundation, Aarhus C, Denmark ; Department of Plant and Environmental Sciences, University of Copenhagen, Frederiksberg C, Denmark.
Michael G
MG
Palmgren
Centre for Membrane Pumps in Cells and Disease - PUMPKIN, Danish National Research Foundation, Aarhus C, Denmark ; Department of Molecular Biology, Aarhus University, Aarhus C, Denmark.
Poul
P
Nissen
Department of Mathematical Sciences, University of Copenhagen, Copenhagen Ø, Denmark.
Carsten
C
Wiuf
Centre for Membrane Pumps in Cells and Disease - PUMPKIN, Danish National Research Foundation, Aarhus C, Denmark ; Bioinformatics Research Centre, Aarhus University, Aarhus C, Denmark.
Christian N S
CN
Pedersen
D000465:Algorithms; D000595:Amino Acid Sequence; D001185:Artificial Intelligence; D019295:Computational Biology / Q000379:methods; D030562:Databases, Protein; D016015:Logistic Models; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein / Q000379:methods*; D012984:Software