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Using machine learning techniques, we construct predictive models to discriminate fallers and non-fallers. Through controlled feature selection, we identified the most salient predictors of patient falls including gait speed, Hoehn and Yahr stage, postural instability and gait difficulty-related measurements. The model-based and model-free analytical methods we employed included logistic regression, random forests, support vector machines, and XGboost. The reliability of the forecasts was assessed by internal statistical (5-fold) cross validation as well as by external out-of-bag validation. Four specific challenges were addressed in the study: Challenge 1, develop a protocol for harmonizing and aggregating complex, multisource, and multi-site Parkinson\u2019s disease data; Challenge 2, identify salient predictive features associated with specific clinical traits, e.g., patient falls; Challenge 3, forecast patient falls and evaluate the classification performance; and Challenge 4, predict tremor dominance (TD) vs. posture instability and gait difficulty (PIGD). Our findings suggest that, compared to other approaches, model-free machine learning based techniques provide a more reliable clinical outcome forecasting of falls in Parkinson\u2019s patients, for example, with a classification accuracy of about 70\u201380%.<\/jats:p>","DOI":"10.1038\/s41598-018-24783-4","type":"journal-article","created":{"date-parts":[[2018,5,1]],"date-time":"2018-05-01T10:10:52Z","timestamp":1525169452000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":122,"title":["Model-based and Model-free Machine Learning Techniques for Diagnostic Prediction and Classification of Clinical Outcomes in Parkinson\u2019s Disease"],"prefix":"10.1038","volume":"8","author":[{"given":"Chao","family":"Gao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanbo","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuo","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolaas I.","family":"Bohnen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1133-7202","authenticated-orcid":false,"given":"Martijn L. 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