category
bioRxiv
date
Feb 25, 2026
slug
status
Published
summary
1) 首次将RNA基础模型应用于子宫内膜异位症分类,跨队列预测性能提升20%;2) 开发CA-IG解释方法实现无需微调的基因层面可解释性;3) 识别出跨队列稳定的疾病相关基因候选靶点
tags
测序技术
type
Post
📄 原文题目
RNA foundation models enable generalizable endometriosis disease classification and stable gene-level interpretation
🔗 原文链接
💡 AI 核心解读
1) 首次将RNA基础模型应用于子宫内膜异位症分类,跨队列预测性能提升20%;2) 开发CA-IG解释方法实现无需微调的基因层面可解释性;3) 识别出跨队列稳定的疾病相关基因候选靶点
📝 英文原版摘要
Endometriosis is a chronic inflammatory condition with significant diagnostic delays impacting one in ten reproductive age women worldwide. While machine learning (ML) models trained on transcriptomic data show promise for disease prediction, limited generalizability across independent patient cohorts has hindered clinical translation. Foundations models (FMs) pretrained on large-scale transcriptomic data offer promise to learn transferrable, biologically meaningful representations that could support cross-cohort predictions. We assembled a 12-cohort bulk RNA-seq benchmark (334 samples) and developed a computationally efficient pipeline to test whether FMs improve endometriosis classification, an approach not previously applied to this disease. Using AutoXAI4Omics with cohort-aware validation, we compared embeddings derived from five state-of-the-art RNA FMs against TPM baselines. In cross-cohort prediction, FM embeddings significantly improved performance, achieving a weighted F1-score of 0.83 vs. 0.68 for the baseline. To allow gene-level interpretation of FM embedding models, we introduce classified-aligned integrated gradients (CA-IG), an interpretability approach aligning gene-level attributions to the downstream classifier without end-to-end fine-tuning. CA-IG revealed a conserved set of predictive genes from FM embeddings across cohort-validation regimes, contrasting with unstable baseline explainability, suggesting that FM embeddings prioritized transferable disease-related signal over cohort-specific effects. These genes include novel candidates that converge on biologically plausible pathways for endometriosis.
- 作者:NotionNext
- 链接:https://tangly1024.com/article/31348bd6-1f96-8133-ba93-efb1aa245136
- 声明:本文采用 CC BY-NC-SA 4.0 许可协议,转载请注明出处。
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