A Machine Learning Approach to Automated Gait Analysis for the Noldus Catwalk System

Objective: Gait analysis of animal disease models can provide valuable insights into in vivo compound effects and thus help in preclinical drug development. The purpose of this paper is to establish a computational gait analysis approach for the Noldus Catwalk system, in which footprints are automatically captured and stored. Methods: We present a - to our knowledge - first machine learning based approach for the Catwalk system, which comprises a step decomposition, definition and extraction of meaningful features, multivariate step sequence alignment, feature selection, and training of different classifiers (gradient boosting machine, random forest, and elastic net). Results: Using animal-wise leave-one-out cross validation we demonstrate that with our method we can reliable separate movement patterns of a putative Parkinson's disease animal model and several control groups. Furthermore, we show that we can predict the time point after and the type of different brain lesions and can even forecast the brain region, where the intervention was applied. We provide an in-depth analysis of the features involved into our classifiers via statistical techniques for model interpretation. Conclusion: A machine learning method for automated analysis of data from the Noldus Catwalk system was established. Significance: Our works shows the ability of machine learning to discriminate pharmacologically relevant animal groups based on their walking behavior in a multivariate manner. Further interesting aspects of the approach include the ability to learn from past experiments, improve with more data arriving and to make predictions for single animals in future studies.

[1]  Björn Krüger,et al.  One Small Step for a Man: Estimation of Gender, Age and Height from Recordings of One Step by a Single Inertial Sensor , 2015, Sensors.

[2]  J. Friedman Stochastic gradient boosting , 2002 .

[3]  Y. Benjamini,et al.  THE CONTROL OF THE FALSE DISCOVERY RATE IN MULTIPLE TESTING UNDER DEPENDENCY , 2001 .

[4]  Toni Giorgino,et al.  Computing and Visualizing Dynamic Time Warping Alignments in R: The dtw Package , 2009 .

[5]  J. Beitz Parkinson's disease: a review. , 2014, Frontiers in bioscience.

[6]  J. P. Huston,et al.  The unilateral 6-hydroxydopamine lesion model in behavioral brain research. Analysis of functional deficits, recovery and treatments , 1996, Progress in Neurobiology.

[7]  J. Trojanowski,et al.  Pathological α-Synuclein Transmission Initiates Parkinson-like Neurodegeneration in Nontransgenic Mice , 2012, Science.

[8]  Jaewoo Jung,et al.  The Interpretation of Spectral Entropy Based Upon Rate Distortion Functions , 2006, 2006 IEEE International Symposium on Information Theory.

[9]  Huan Liu,et al.  Efficient Feature Selection via Analysis of Relevance and Redundancy , 2004, J. Mach. Learn. Res..

[10]  H. Lindgren,et al.  A model of l-DOPA-induced dyskinesia in 6-hydroxydopamine lesioned mice: relation to motor and cellular parameters of nigrostriatal function , 2004, Neurobiology of Disease.

[11]  Pablo Tamayo,et al.  Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[12]  Tomohiro Shirakawa,et al.  Gait analysis and machine learning classification on healthy subjects in normal walking , 2015 .

[13]  K. A. Clarke,et al.  Gait Analysis in the Mouse , 1999, Physiology & Behavior.

[14]  Henning Müller,et al.  Applying Machine Learning to Gait Analysis Data for Disease Identification , 2015, MIE.

[15]  Eric R. Ziegel,et al.  The Elements of Statistical Learning , 2003, Technometrics.

[16]  P. Yu,et al.  Gait analysis in rats with peripheral nerve injury , 2001, Muscle & nerve.

[17]  Trevor Hastie,et al.  Regularization Paths for Generalized Linear Models via Coordinate Descent. , 2010, Journal of statistical software.

[18]  Robert L. Parker,et al.  psd: Adaptive, sine multitaper power spectral density estimation for R , 2014, Comput. Geosci..

[19]  Koen Van Laere,et al.  Automated quantitative gait analysis in animal models of movement disorders , 2010, BMC Neuroscience.

[20]  Leo Breiman,et al.  Random Forests , 2001, Machine Learning.

[21]  Hansjürgen Bratzke,et al.  Stages in the development of Parkinson’s disease-related pathology , 2004, Cell and Tissue Research.

[22]  Andreas Zell,et al.  Automated classification of the behavior of rats in the forced swimming test with support vector machines , 2008, Neural Networks.

[23]  Rich Caruana,et al.  An Empirical Comparison of Supervised Learning Algorithms Using Different Performance Metrics , 2005 .