Jordi Abante

Mohammad Usman, Olga Varea, Petia Radeva et al.

Neurodegenerative diseases (NDDs) are complex and lack effective treatment due to their poorly understood mechanism. The increasingly used data analysis from Single nucleus RNA Sequencing (snRNA-seq) allows to explore transcriptomic events at a single cell level, yet face challenges in interpreting the mechanisms underlying a disease. On the other hand, Neural Network (NN) models can handle complex data to offer insights but can be seen as black boxes with poor interpretability. In this context, explainable AI (XAI) emerges as a solution that could help to understand disease-associated mechanisms when combined with efficient NN models. However, limited research explores XAI in single-cell data. In this work, we implement a method for identifying disease-related genes and the mechanistic explanation of disease progression based on NN model combined with SHAP. We analyze available Huntington's disease (HD) data to identify both HD-altered genes and mechanisms by adding Gene Set Enrichment Analysis (GSEA) comparing two methods, differential gene expression analysis (DGE) and NN combined with SHAP approach. Our results show that DGE and SHAP approaches offer both common and differential sets of altered genes and pathways, reinforcing the usefulness of XAI methods for a broader perspective of disease.

Berta Ros, Mireia Olives-Verger, Caterina Fuses et al.

Calcium imaging allows for the parallel measurement of large neuronal populations in a spatially resolved and minimally invasive manner, and has become a gold-standard for neuronal functionality. While deep generative models have been successfully applied to study the activity of neuronal ensembles, their potential for learning single-neuron representations from calcium imaging fluorescence traces remains largely unexplored, and batch effects remain an important hurdle. To address this, we explore supervised variational autoencoder architectures that learn compact representations of individual neurons from fluorescent traces without relying on spike inference algorithms. We find that this approach outperforms state-of-the-art models, preserving biological variability while mitigating batch effects. Across simulated and experimental datasets, this framework enables robust visualization, clustering, and interpretation of single-neuron dynamics.