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Analysis of mass spectrometry data from the secretome of an explant model of articular cartilage exposed to pro-inflammatory and anti-inflammatory stimuli using machine learning

Swan, Anna L.; Hillier, Kirsty L.; Smith, Julia R.; Allaway, David; Liddell, Susan; Bacardit, Jaume; Mobasheri, Ali

Authors

Anna L. Swan

Kirsty L. Hillier

Julia R. Smith

David Allaway

Susan Liddell

Jaume Bacardit

Ali Mobasheri ali.mobasheri.manuscripts@gmail.com



Abstract

Background: Osteoarthritis (OA) is an inflammatory disease of synovial joints involving the loss and degeneration of articular cartilage. The gold standard for evaluating cartilage loss in OA is the measurement of joint space width on standard radiographs. However, in most cases the diagnosis is made well after the onset of the disease, when the symptoms are well established. Identification of early biomarkers of OA can facilitate earlier diagnosis, improve disease monitoring and predict responses to therapeutic interventions.

Methods: This study describes the bioinformatic analysis of data generated from high throughput proteomics for identification of potential biomarkers of OA. The mass spectrometry data was generated using a canine explant model of articular cartilage treated with the pro-inflammatory cytokine interleukin 1 β (IL-1β). The bioinformatics analysis involved the application of machine learning and network analysis to the proteomic mass spectrometry data. A rule based machine learning technique, BioHEL, was used to create a model that classified the samples into their relevant treatment groups by identifying those proteins that separated samples into their respective groups. The proteins identified were considered to be potential biomarkers. Protein networks were also generated; from these networks, proteins pivotal to the classification were identified.

Results: BioHEL correctly classified eighteen out of twenty-three samples, giving a classification accuracy of 78.3% for the dataset. The dataset included the four classes of control, IL-1β, carprofen, and IL-1β and carprofen together. This exceeded the other machine learners that were used for a comparison, on the same dataset, with the exception of another rule-based method, JRip, which performed equally well. The proteins that were most frequently used in rules generated by BioHEL were found to include a number of relevant proteins including matrix metalloproteinase 3, interleukin 8 and matrix gla protein.

Conclusions: Using this protocol, combining an in vitro model of OA with bioinformatics analysis, a number of relevant extracellular matrix proteins were identified, thereby supporting the application of these bioinformatics tools for analysis of proteomic data from in vitro models of cartilage degradation.

Citation

Swan, A. L., Hillier, K. L., Smith, J. R., Allaway, D., Liddell, S., Bacardit, J., & Mobasheri, A. (2013). Analysis of mass spectrometry data from the secretome of an explant model of articular cartilage exposed to pro-inflammatory and anti-inflammatory stimuli using machine learning. BMC Musculoskeletal Disorders, 14, doi:10.1186/1471-2474-14-349

Journal Article Type Article
Publication Date Jan 1, 2013
Deposit Date Mar 27, 2014
Publicly Available Date Mar 27, 2014
Journal BMC Musculoskeletal Disorders
Electronic ISSN 1471-2474
Publisher Humana Press
Peer Reviewed Peer Reviewed
Volume 14
Article Number 349
DOI https://doi.org/10.1186/1471-2474-14-349
Public URL http://eprints.nottingham.ac.uk/id/eprint/2700
Publisher URL http://www.biomedcentral.com/1471-2474/14/349
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0





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