arXiv:2602.10168q-bio.QMcs.AI2026-02

EVA是首个跨物种免疫学基础模型,融合多组学与病理图像数据,助力药物研发全流程。

EVA: Towards a universal model of the immune system

  • 构建跨物种、多模态免疫系统统一表征,整合转录组与组织病理数据
  • 在39项药物研发任务中实现顶尖性能,模型规模越大效果越优
  • 开源转录组版EVA,适合免疫疾病研究者和药物开发团队使用

将基础模型应用于自身免疫性疾病转化研究,需要能捕捉多细胞互作复杂表型的患者级多模态表示。然而,现有生物基础模型多聚焦单细胞分辨率,且评估指标常与真实药物研发任务脱节。本文提出EVA,首个跨物种、多模态的免疫与炎症领域基础模型,该治疗领域共享致病机制,为迁移学习提供独特机遇。EVA对齐跨物种、平台与分辨率的转录组数据,并融合组织病理数据,生成丰富统一的患者表征。我们建立了清晰的扩展规律,证明增大模型规模与算力可提升预训练及下游任务表现。引入涵盖药物研发全链条的39项评估任务:零样本靶点效力与基因功能预测用于发现阶段,跨物种或跨疾病分子扰动用于临床前开发,患者分层及治疗应答/疾病活动度预测用于临床试验应用。在这些任务上,EVA显著优于多个先进生物基础模型与基线方法,各项任务均达当前最优。通过机制可解释性分析,揭示了跨物种与技术间的生物意义特征关联。我们开放发布EVA转录组版本,以加速自身免疫疾病研究。

原文摘要 · Abstract (English)

The effective application of foundation models to translational research in immune-mediated diseases requires multimodal patient-level representations that can capture complex phenotypes emerging from multicellular interactions. Yet most current biological foundation models focus only on single-cell resolution and are evaluated on technical metrics often disconnected from actual drug development tasks and challenges. Here, we introduce EVA, the first cross-species, multimodal foundation model of immunology and inflammation, a therapeutic area where shared pathogenic mechanisms create unique opportunities for transfer learning. EVA harmonizes transcriptomics data across species, platforms, and resolutions, and integrates histology data to produce rich, unified patient representations. We establish clear scaling laws, demonstrating that increasing model size and compute translates to improvements in both pretraining and downstream tasks performance. We introduce a comprehensive evaluation suite of 39 tasks spanning the drug development pipeline: zero-shot target efficacy and gene function prediction for discovery, cross-species or cross-diseases molecular perturbations for preclinical development, and patient stratification with treatment response prediction or disease activity prediction for clinical trials applications. We benchmark EVA against several state-of-the-art biological foundation models and baselines on these tasks, and demonstrate state-of-the-art results on each task category. Using mechanistic interpretability, we further identify biological meaningful features, revealing intertwined representations across species and technologies. We release an open version of EVA for transcriptomics to accelerate research on immune-mediated diseases.

免疫模型多模态药物研发基础模型

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