Fan Zhang1,2, Melissa Petersen1,2, Leigh Johnson1, James Hall1, Sid E O'Bryant1. 1. Institute for Translational Research, Department of Pharmacology & Neuroscience, University of North Texas Health Science Center, Fort Worth, TX, USA. 2. Department of Family Medicine, University of North Texas Health Science Center, Fort Worth, TX, USA.
Abstract
BACKGROUND: There is a need for more reliable diagnostic tools for the early detection of Alzheimer's disease (AD). This can be a challenge due to a number of factors and logistics making machine learning a viable option. OBJECTIVE: In this paper, we present on a Support Vector Machine Leave-One-Out Recursive Feature Elimination and Cross Validation (SVM-RFE-LOO) algorithm for use in the early detection of AD and show how the SVM-RFE-LOO method can be used for both classification and prediction of AD. METHODS: Data were analyzed on n = 300 participants (n = 150 AD; n = 150 cognitively normal controls). Serum samples were assayed via a multi-plex biomarker assay platform using electrochemiluminescence (ECL). RESULTS: The SVM-RFE-LOO method reduced the number of features in the model from 21 to 16 biomarkers and achieved an area under the curve (AUC) of 0.980 with a sensitivity of 94.0% and a specificity of 93.3%. When the classification and prediction performance of SVM-RFE-LOO was compared to that of SVM and SVM-RFE, we found similar performance across the models; however, the SVM-RFE-LOO method utilized fewer markers. CONCLUSION: We found that 1) the SVM-RFE-LOO is suitable for analyzing noisy high-throughput proteomic data, 2) it outperforms SVM-RFE in the robustness to noise and in the ability to recover informative features, and 3) it can improve the prediction performance. Our recursive feature elimination model can serve as a general model for biomarker discovery in other diseases.
BACKGROUND: There is a need for more reliable diagnostic tools for the early detection of Alzheimer's disease (AD). This can be a challenge due to a number of factors and logistics making machine learning a viable option. OBJECTIVE: In this paper, we present on a Support Vector Machine Leave-One-Out Recursive Feature Elimination and Cross Validation (SVM-RFE-LOO) algorithm for use in the early detection of AD and show how the SVM-RFE-LOO method can be used for both classification and prediction of AD. METHODS: Data were analyzed on n = 300 participants (n = 150 AD; n = 150 cognitively normal controls). Serum samples were assayed via a multi-plex biomarker assay platform using electrochemiluminescence (ECL). RESULTS: The SVM-RFE-LOO method reduced the number of features in the model from 21 to 16 biomarkers and achieved an area under the curve (AUC) of 0.980 with a sensitivity of 94.0% and a specificity of 93.3%. When the classification and prediction performance of SVM-RFE-LOO was compared to that of SVM and SVM-RFE, we found similar performance across the models; however, the SVM-RFE-LOO method utilized fewer markers. CONCLUSION: We found that 1) the SVM-RFE-LOO is suitable for analyzing noisy high-throughput proteomic data, 2) it outperforms SVM-RFE in the robustness to noise and in the ability to recover informative features, and 3) it can improve the prediction performance. Our recursive feature elimination model can serve as a general model for biomarker discovery in other diseases.
Authors: Sid E O'Bryant; Fan Zhang; Melissa Petersen; James R Hall; Leigh A Johnson; Kristine Yaffe; Meredith Braskie; Rocky Vig; Arthur W Toga; Robert A Rissman Journal: J Alzheimers Dis Date: 2022 Impact factor: 4.160