The factors that determine Serum Thyrotropin (TSH) levels have been examined through different methods, using different covariates. However, the use of machine learning methods has so far not been studied in population databases like NHANES (National Health and Nutritional Examination Survey) to predict TSH. In this study, we performed a comparative analysis of different machine learning methods like Linear regression, Random forest, Support vector machine, multilayer perceptron and stacking regression to predict TSH and classify individuals with normal, low and high TSH levels. We considered Free T4, Anti-TPO antibodies, T3, Body Mass Index (BMI), Age and Ethnicity as the predictor variables. A total of 9818 subjects were included in this comparative analysis. We used coefficient of determination (r 2 ) value to compare the results for predicting the TSH and show that the Random Forest, Gradient Boosting and Stacking Regression perform equally well in predicting TSH and achieve the highest r 2 value = 0.13, with mean absolute error of 0.78. Moreover, we found that Anti-TPO is the most important feature in predicting TSH followed by Age, BMI, T3 and Free-T4 for the regression analysis. While classifying TSH into normal, high or low levels, our comparative analysis also shows that Random forest performs the best in the classification study, performed with individuals with normal, high and low levels of TSH. We found the following Areas Under Curve (AUC); for low TSH, AUC = 0.61, normal TSH, AUC = 0.61 and elevated TSH AUC = 0.69. Additionally, we found that Anti-TPO was the most important feature in classifying TSH. In this study, we suggest that artificial intelligence and machine learning methods might offer an insight into the complex hypothalamic-pituitary -thyroid axis and may be an invaluable tool that guides us in making appropriate therapeutic decisions (thyroid hormone dosing) for the individual patient.

IntroductionThe integrity of the intestinal epithelium is crucial for human health and is harmed in autism spectrum disorder (ASD). An aberrant gut microbial composition resulting in gut-derived metabolic toxins was found to damage the intestinal epithelium, jeopardizing tissue integrity. These toxins further reach the brain via the gut-brain axis, disrupting the normal function of the brain. A mechanistic understanding of metabolic disturbances in the brain and gut is essential to design effective therapeutics and early intervention to block disease progression. Herein, we present a novel computational framework integrating constraint based tissue specific metabolic (CBM) model and whole-body physiological pharmacokinetics (PBPK) modeling for ASD. Furthermore, the role of gut microbiota, diet, and oxidative stress is analyzed in ASD.MethodsA representative gut model capturing host-bacteria and bacteria-bacteria interaction was developed using CBM techniques and patient data. Simultaneously, a PBPK model of toxin metabolism was assembled, incorporating multi-scale metabolic information. Furthermore, dynamic flux balance analysis was performed to integrate CBM and PBPK. The effectiveness of a probiotic and dietary intervention to improve autism symptoms was tested on the integrated model.ResultsThe model accurately highlighted critical metabolic pathways of the gut and brain that are associated with ASD. These include central carbon, nucleotide, and vitamin metabolism in the host gut, and mitochondrial energy and amino acid metabolisms in the brain. The proposed dietary intervention revealed that a high-fiber diet is more effective than a western diet in reducing toxins produced inside the gut. The addition of probiotic bacteria Lactobacillus acidophilus, Bifidobacterium longum longum, Akkermansia muciniphila, and Prevotella ruminicola to the diet restores gut microbiota balance, thereby lowering oxidative stress in the gut and brain.ConclusionThe proposed computational framework is novel in its applicability, as demonstrated by the determination of the whole-body distribution of ROS toxins and metabolic association in ASD. In addition, it emphasized the potential for developing novel therapeutic strategies to alleviate autism symptoms. Notably, the presented integrated model validates the importance of combining PBPK modeling with COBRA -specific tissue details for understanding disease pathogenesis.