Enhancing Fever of unknown origin Diagnosis: Machine Learning Approaches to Predict Metagenomic next-generation sequencing Positivity

Zhi Gao YONGFANG JIANG Mengxuan Chen Weihang Wang Qiyao Liu Jing Ma ^*

• Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China

Metagenomic next-generation sequencing (mNGS) can potentially detect various pathogenic microorganisms without bias to improve the diagnostic rate of fever of unknown origin (FUO), but there are no effective methods to predict mNGS-positive results. This study aimed to develop an interpretable machine learning algorithm for the effective prediction of mNGS results in patients with FUO.A clinical dataset from a large medical institution was used to develop and compare the performance of several predictive models, namely eXtreme Gradient Boosting (XGBoost), Light Gradient-Boosting Machine (LightGBM), and Random Forest, and the Shapley additive explanation (SHAP) method was employed to interpret and analyze the results.The mNGS-positive rate among 284 patients with FUO reached 64.1%. Overall, the LightGBM-based model exhibited the best comprehensive predictive performance, with areas under the curve of 0.84 and 0.93 for the training and validation sets, respectively. Using the SHAP method, the five most important factors for predicting mNGS-positive results were albumin, procalcitonin, blood culture, disease type, and sample type.The validated LightGBM-based predictive model could have practical clinical value in enhancing the application of mNGS in the etiological diagnosis of FUO, representing a powerful tool to optimize the timing of mNGS.