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      Predicting anterior cruciate ligament failure load with T 2* relaxometry and machine learning as a prospective imaging biomarker for revision surgery

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          Abstract

          Non-invasive methods to document healing anterior cruciate ligament (ACL) structural properties could potentially identify patients at risk for revision surgery. The objective was to evaluate machine learning models to predict ACL failure load from magnetic resonance images (MRI) and to determine if those predictions were related to revision surgery incidence. It was hypothesized that the optimal model would demonstrate a lower mean absolute error (MAE) than the benchmark linear regression model, and that patients with a lower estimated failure load would have higher revision incidence 2 years post-surgery. Support vector machine, random forest, AdaBoost, XGBoost, and linear regression models were trained using MRI T 2* relaxometry and ACL tensile testing data from minipigs (n = 65). The lowest MAE model was used to estimate ACL failure load for surgical patients at 9 months post-surgery (n = 46) and dichotomized into low and high score groups via Youden’s J statistic to compare revision incidence. Significance was set at alpha = 0.05. The random forest model decreased the failure load MAE by 55% (Wilcoxon signed-rank test: p = 0.01) versus the benchmark. The low score group had a higher revision incidence (21% vs. 5%; Chi-square test: p = 0.09). ACL structural property estimates via MRI may provide a biomarker for clinical decision making.

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            Gene selection for cancer classification using support vector machines

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              Bias in random forest variable importance measures: Illustrations, sources and a solution

              Background Variable importance measures for random forests have been receiving increased attention as a means of variable selection in many classification tasks in bioinformatics and related scientific fields, for instance to select a subset of genetic markers relevant for the prediction of a certain disease. We show that random forest variable importance measures are a sensible means for variable selection in many applications, but are not reliable in situations where potential predictor variables vary in their scale of measurement or their number of categories. This is particularly important in genomics and computational biology, where predictors often include variables of different types, for example when predictors include both sequence data and continuous variables such as folding energy, or when amino acid sequence data show different numbers of categories. Results Simulation studies are presented illustrating that, when random forest variable importance measures are used with data of varying types, the results are misleading because suboptimal predictor variables may be artificially preferred in variable selection. The two mechanisms underlying this deficiency are biased variable selection in the individual classification trees used to build the random forest on one hand, and effects induced by bootstrap sampling with replacement on the other hand. Conclusion We propose to employ an alternative implementation of random forests, that provides unbiased variable selection in the individual classification trees. When this method is applied using subsampling without replacement, the resulting variable importance measures can be used reliably for variable selection even in situations where the potential predictor variables vary in their scale of measurement or their number of categories. The usage of both random forest algorithms and their variable importance measures in the R system for statistical computing is illustrated and documented thoroughly in an application re-analyzing data from a study on RNA editing. Therefore the suggested method can be applied straightforwardly by scientists in bioinformatics research.
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                Author and article information

                Contributors
                braden_fleming@brown.edu
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                2 March 2023
                2 March 2023
                2023
                : 13
                : 3524
                Affiliations
                [1 ]GRID grid.240588.3, ISNI 0000 0001 0557 9478, Department of Orthopaedics, , Warren Alpert Medical School of Brown University/Rhode Island Hospital, ; Coro West, Suite 402, 1 Hoppin St, Providence, RI 02903 USA
                [2 ]GRID grid.2515.3, ISNI 0000 0004 0378 8438, Division of Sports Medicine, Department of Orthopaedic Surgery, , Boston Children’s Hospital, Harvard Medical School, ; Boston, MA USA
                [3 ]GRID grid.40263.33, ISNI 0000 0004 1936 9094, Department of Neuroscience, Division of Biology and Medicine, , Brown University, ; Providence, RI USA
                Article
                30637
                10.1038/s41598-023-30637-5
                9981601
                36864112
                8448470a-a4a3-4e91-b4fb-72a4d6e00392
                © The Author(s) 2023

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 6 June 2022
                : 27 February 2023
                Funding
                Funded by: RIH Orthopedic Foundation
                Funded by: Lucy Lippitt Endowment of Brown University
                Funded by: FundRef http://dx.doi.org/10.13039/100000057, National Institute of General Medical Sciences;
                Award ID: P30-GM122732
                Funded by: National Institutes of Health, United States
                Award ID: K99/R00-AR069094
                Award Recipient :
                Funded by: Translational Research Program at Boston Children's Hospital
                Funded by: Children's Hospital Orthopaedic Surgery Foundation
                Funded by: Children’s Hospital Sports Medicine Foundation
                Funded by: Football Players Health Study at Harvard University
                Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: R01-AR065462
                Categories
                Article
                Custom metadata
                © The Author(s) 2023

                Uncategorized
                predictive markers,magnetic resonance imaging,machine learning
                Uncategorized
                predictive markers, magnetic resonance imaging, machine learning

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