You Only Train Once: Differentiable Subset Selection for Omics Data

Fuente: arXiv
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Autores principales: Chopard, Daphné, Gonçalves, Jorge da Silva, Cannistraci, Irene, Sutter, Thomas M., Vogt, Julia E.
Formato: Preprint
Publicado: 2025
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author Chopard, Daphné
Gonçalves, Jorge da Silva
Cannistraci, Irene
Sutter, Thomas M.
Vogt, Julia E.
author_facet Chopard, Daphné
Gonçalves, Jorge da Silva
Cannistraci, Irene
Sutter, Thomas M.
Vogt, Julia E.
contents 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.
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id arxiv_https___arxiv_org_abs_2512_17678
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle You Only Train Once: Differentiable Subset Selection for Omics Data
Chopard, Daphné
Gonçalves, Jorge da Silva
Cannistraci, Irene
Sutter, Thomas M.
Vogt, Julia E.
Machine Learning
Artificial Intelligence
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.
title You Only Train Once: Differentiable Subset Selection for Omics Data
topic Machine Learning
Artificial Intelligence
url https://arxiv.org/abs/2512.17678