title: 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.
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.
authors: Anna L
authors: AL
authors: Swan
authors: Kirsty L
authors: KL
authors: Hillier
authors: Julia R
authors: JR
authors: Smith
authors: David
authors: D
authors: Allaway
authors: Susan
authors: S
authors: Liddell
authors: Jaume
authors: J
authors: Bacardit
authors: Musculoskeletal Research Group, School of Veterinary Medicine and Science, Faculty of Medicine and Health Science, University of Nottingham, Sutton Bonington Campus, Leicestershire, LE12 5RD, UK. ali.mobasheri.manuscripts@gmail.com.
authors: Ali
authors: A
authors: Mobasheri
mesh_terms: D000818:Animals; D001185:Artificial Intelligence; D002358:Cartilage, Articular / Q000378:metabolism*; D004285:Dogs; D053583:Interleukin-1beta; D008297:Male; D013058:Mass Spectrometry; D010003:Osteoarthritis / Q000209:etiology; D011506:Proteins / Q000378:metabolism*; D020543:Proteome
chemical_list: D053583:Interleukin-1beta; D011506:Proteins; D020543:Proteome