Jorge da Silva Gonçalves

Daphné Chopard, Jorge da Silva Gonçalves, Irene Cannistraci et al.

Selecting compact and informative gene subsets from single-cell transcriptomic data is essential for biomarker discovery, improving interpretability, and cost-effective profiling. However, most existing feature selection approaches either operate as multi-stage pipelines or rely on post hoc feature attribution, making selection and prediction weakly coupled. In this work, we present YOTO (you only train once), an end-to-end framework that jointly identifies discrete gene subsets and performs prediction within a single differentiable architecture. In our model, the prediction task directly guides which genes are selected, while the learned subsets, in turn, shape the predictive representation. This closed feedback loop enables the model to iteratively refine both what it selects and how it predicts during training. Unlike existing approaches, YOTO enforces sparsity so that only the selected genes contribute to inference, eliminating the need to train additional downstream classifiers. Through a multi-task learning design, the model learns shared representations across related objectives, allowing partially labeled datasets to inform one another, and discovering gene subsets that generalize across tasks without additional training steps. We evaluate YOTO on two representative single-cell RNA-seq datasets, showing that it consistently outperforms state-of-the-art baselines. These results demonstrate that sparse, end-to-end, multi-task gene subset selection improves predictive performance and yields compact and meaningful gene subsets, advancing biomarker discovery and single-cell analysis.

Jorge da Silva Gonçalves, Laura Manduchi, Moritz Vandenhirtz et al.

Generative modeling and clustering are conventionally distinct tasks in machine learning. Variational Autoencoders (VAEs) have been widely explored for their ability to integrate both, providing a framework for generative clustering. However, while VAEs can learn meaningful cluster representations in latent space, they often struggle to generate high-quality samples. This paper addresses this problem by introducing TreeDiffusion, a deep generative model that conditions diffusion models on learned latent hierarchical cluster representations from a VAE to obtain high-quality, cluster-specific generations. Our approach consists of two steps: first, a VAE-based clustering model learns a hierarchical latent representation of the data. Second, a cluster-aware diffusion model generates realistic images conditioned on the learned hierarchical structure. We systematically compare the generative capabilities of our approach with those of alternative conditioning strategies. Empirically, we demonstrate that conditioning diffusion models on hierarchical cluster representations improves the generative performance on real-world datasets compared to other approaches. Moreover, a key strength of our method lies in its ability to generate images that are both representative and specific to each cluster, enabling more detailed visualization of the learned latent structure. Our approach addresses the generative limitations of VAE-based clustering approaches by leveraging their learned structure, thereby advancing the field of generative clustering.