BACKGROUND & OBJECTIVES: Mental health disorders pose an increasing public health challenge worsened by the COVID-19 pandemic. The pandemic highlighted gaps in preparedness, emphasizing the need for early identification of at-risk groups and targeted interventions. This study aims to develop a risk assessment tool for anxiety, depression, and self-perceived stress using machine learning (ML) and explainable AI to identify key risk factors and stratify the population into meaningful risk profiles. METHODS: We utilized a cohort of 9291 individuals from Northern Spain, with extensive post-COVID-19 mental health surveys. ML classification algorithms predicted depression, anxiety, and self-reported stress in three classes: healthy, mild, and severe outcomes. A novel combination of SHAP (SHapley Additive exPlanations) and UMAP (Uniform Manifold Approximation and Projection) was employed to interpret model predictions and facilitate the identification of high-risk phenotypic clusters. RESULTS: The mean macro-averaged one-vs-one AUROC was 0.77 (± 0.01) for depression, 0.72 (± 0.01) for anxiety, and 0.73 (± 0.02) for self-perceived stress. Key risk factors included poor self-reported health, chronic mental health conditions, and poor social support. High-risk profiles, such as women with reduced sleep hours, were identified for self-perceived stress. Binary classification of healthy vs. at-risk classes yielded F1-Scores over 0.70. CONCLUSIONS: Combining SHAP with UMAP for risk profile stratification offers valuable insights for developing effective interventions and shaping public health policies. This data-driven approach to mental health preparedness, when validated in real-world scenarios, can significantly address the mental health impact of public health crises like COVID-19.

UNLABELLED: Single nucleotide polymorphisms (SNPs) are the most widely used marker in studies to assess associations between genetic variants and complex traits or diseases. They are also becoming increasingly important in the study of the evolution and history of humans and other species. The analysis and processing of SNPs obtained thanks to high-throughput technologies imply the time consuming and costly use of different, complex and usually format-incompatible software. SNPator is a user-friendly web-based SNP data analysis suite that integrates, among many other algorithms, the most common steps of a SNP association study. It frees the user from the need to have large computer facilities and an in depth knowledge of genetic software installation and management. Genotype data is directly read from the output files of the usual genotyping platforms. Phenotypic data on the samples can also be easily uploaded. Many different quality control and analysis procedures can be performed either by using built-in SNPator algorithms or by calling standard genetic software. AVAILABILITY: Access is granted from the SNPator webpage http://www.snpator.org.