Benchmarking of Machine Learning classifiers on plasma proteomic for COVID-19 severity prediction through interpretable artificial intelligence

The SARS-CoV-2 pandemic highlighted the need for software tools that could facilitate patient triage regarding potential disease severity or even death. In this article, an ensemble of Machine Learning (ML) algorithms is evaluated in terms of predicting the severity of their condition using plasma proteomics and clinical data as input. An overview of AI-based technical developments to support COVID-19 patient management is presented outlining the landscape of relevant technical developments. Based on this review, the use of an ensemble of ML algorithms that analyze clinical and biological data (i.e., plasma proteomics) of COVID-19 patients is designed and deployed to evaluate the potential use of AI for early COVID-19 patient triage. The proposed pipeline is evaluated using three publicly available datasets for training and testing. Three ML "tasks" are defined, and several algorithms are tested through a hyperparameter tuning method to identify the highest-performance models. As overfitting is one of the typical pitfalls for such approaches (mainly due to the size of the training/validation datasets), a variety of evaluation metrics are used to mitigate this risk. In the evaluation procedure, recall scores ranged from 0.6 to 0.74 and F1-score from 0.62 to 0.75. The best performance is observed via Multi-Layer Perceptron (MLP) and Support Vector Machines (SVM) algorithms. Additionally, input data (proteomics and clinical data) were ranked based on corresponding Shapley additive explanation (SHAP) values and evaluated for their prognosticated capacity and immuno-biological credence. This "interpretable" approach revealed that our ML models could discern critical COVID-19 cases predominantly based on patient's age and plasma proteins on B cell dysfunction, hyper-activation of inflammatory pathways like Toll-like receptors, and hypo-activation of developmental and immune pathways like SCF/c-Kit signaling. Finally, the herein computational workflow is corroborated in an independent dataset and MLP superiority along with the implication of the abovementioned predictive biological pathways are corroborated. Regarding limitations of the presented ML pipeline, the datasets used in this study contain less than 1000 observations and a significant number of input features hence constituting a high-dimensional low-sample (HDLS) dataset which could be sensitive to overfitting. An advantage of the proposed pipeline is that it combines biological data (plasma proteomics) with clinical-phenotypic data. Thus, in principle, the presented approach could enable patient triage in a timely fashion if used on already trained models. However, larger datasets and further systematic validation are needed to confirm the potential clinical value of this approach. The code is available on Github: https://github.com/inab-certh/Predicting-COVID-19-severity-through-interpretable-AI-analysis -of-plasma-proteomics.