title: Gait characterization in golden retriever muscular dystrophy dogs using linear discriminant analysis.
abstract: Accelerometric analysis of gait abnormalities in golden retriever muscular dystrophy (GRMD) dogs is of limited sensitivity, and produces highly complex data. The use of discriminant analysis may enable simpler and more sensitive evaluation of treatment benefits in this important preclinical model.
  
  
  
  Accelerometry was performed twice monthly between the ages of 2 and 12 months on 8 healthy and 20 GRMD dogs. Seven accelerometric parameters were analysed using linear discriminant analysis (LDA). Manipulation of the dependent and independent variables produced three distinct models. The ability of each model to detect gait alterations and their pattern change with age was tested using a leave-one-out cross-validation approach.
  
  
  
  Selecting genotype (healthy or GRMD) as the dependent variable resulted in a model (Model 1) allowing a good discrimination between the gait phenotype of GRMD and healthy dogs. However, this model was not sufficiently representative of the disease progression. In Model 2, age in months was added as a supplementary dependent variable (GRMD_2 to GRMD_12 and Healthy_2 to Healthy_9.5), resulting in a high overall misclassification rate (83.2%). To improve accuracy, a third model (Model 3) was created in which age was also included as an explanatory variable. This resulted in an overall misclassification rate lower than 12%. Model 3 was evaluated using blinded data pertaining to 81 healthy and GRMD dogs. In all but one case, the model correctly matched gait phenotype to the actual genotype. Finally, we used Model 3 to reanalyse data from a previous study regarding the effects of immunosuppressive treatments on muscular dystrophy in GRMD dogs. Our model identified significant effect of immunosuppressive treatments on gait quality, corroborating the original findings, with the added advantages of direct statistical analysis with greater sensitivity and more comprehensible data representation.
  
  
  
  Gait analysis using LDA allows for improved analysis of accelerometry data by applying a decision-making analysis approach to the evaluation of preclinical treatment benefits in GRMD dogs.
authors.affiliation: Atlantic Gene Therapies, INSERM UMR 1089, Nantes, France. bodvael.fraysse@univ-nantes.fr.
authors.forename: Bodvaël
authors.initials: B
authors.lastname: Fraysse
authors.affiliation: INSERM U955-E10 Biology of the NeuroMuscular System, 94000, Créteil, France.|Université Paris-Est, École Nationale Vétérinaire d'Alfort, 94700, Maisons-Alfort, France.|Faculté de Médecine, 94000, Créteil, France.
authors.forename: Inès
authors.initials: I
authors.lastname: Barthélémy
authors.affiliation: LUNAM University, ONIRIS, National College of Veterinary Medicine, Food Science, and Engineering, USC "Sensometrics and Chemometrics Laboratory", Nantes, France.
authors.forename: El Mostafa
authors.initials: EM
authors.lastname: Qannari
authors.affiliation: Atlantic Gene Therapies, INRA UMR 703, ONIRIS, Nantes, France.
authors.forename: Karl
authors.initials: K
authors.lastname: Rouger
authors.affiliation: Nutrition and Endocrinology Unit, ONIRIS, National College of Veterinary Medicine, Food Science, and Engineering, Nantes, France.
authors.forename: Chantal
authors.initials: C
authors.lastname: Thorin
authors.affiliation: INSERM U955-E10 Biology of the NeuroMuscular System, 94000, Créteil, France.|Université Paris-Est, École Nationale Vétérinaire d'Alfort, 94700, Maisons-Alfort, France.|Faculté de Médecine, 94000, Créteil, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Blot
authors.affiliation: Atlantic Gene Therapies, INSERM UMR 1089, Nantes, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Le Guiner
authors.affiliation: Atlantic Gene Therapies, INRA UMR 703, ONIRIS, Nantes, France.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chérel
authors.affiliation: Neuromuscular Physiology and Evaluation Lab, Institute of Myology, Paris, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Hogrel
mesh_terms: D061725:Accelerometry / Q000295:instrumentation / Q000706:statistics & numerical data*; D000367:Age Factors; D000818:Animals; D000066491:Clinical Decision-Making / Q000379:methods; D016002:Discriminant Analysis; D004195:Disease Models, Animal; D018450:Disease Progression; D004285:Dogs; D005684:Gait / Q000187:drug effects* / Q000502:physiology*; D005838:Genotype; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016014:Linear Models; D008297:Male; D009137:Muscular Dystrophy, Animal / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology*; D020388:Muscular Dystrophy, Duchenne / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology*; D010641:Phenotype; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents
keywords: Accelerometry; Animal model; Discriminant analysis; GRMD; Gait assessment; Muscular dystrophy; Treatment evaluation