Plattner Christina, Sturm Gregor, Kühl Anja A, Atreya Raja, Carollo Sandro, Gronauer Raphael, Rieder Dietmar, Günther Michael, Ormanns Steffen, Manzl Claudia, Wirtz Stefan, Meneghetti Asier Rabasco, Hegazy Ahmed N, Patankar Jay V, Carrero Zunamys I, Neurath Markus F, Kather Jakob Nikolas, Becker Christoph, Siegmund Britta, Trajanoski Zlatko
bioRxiv. 2025 Apr 10:2025.03.26.645544. doi: 10.1101/2025.03.26.645544.
Multi-omic and multimodal datasets with detailed clinical annotations offer significant potential to advance our understanding of inflammatory bowel diseases (IBD), refine diagnostics, and enable personalized therapeutic strategies. In this multi-cohort study, we performed an extensive multi-omic and multimodal analysis of 1,002 clinically annotated patients with IBD and non-IBD controls, incorporating whole-exome and RNA sequencing of normal and inflamed gut tissues, serum proteomics, and histopathological assessments from images of H&E-stained tissue sections. Transcriptomic profiles of normal and inflamed tissues revealed distinct site-specific inflammatory signatures in Crohn's disease (CD) and ulcerative colitis (UC). Leveraging serum proteomics, we developed an inflammatory protein severity signature that reflects underlying intestinal molecular inflammation. Furthermore, foundation model-based deep learning accurately predicted histologic disease activity scores from images of H&E-stained intestinal tissue sections, offering a robust tool for clinical evaluation. Our integrative analysis highlights the potential of combining multi-omics and advanced computational approaches to improve our understanding and management of IBD.
带有详细临床注释的多组学和多模态数据集为增进我们对炎症性肠病（IBD）的理解、完善诊断以及制定个性化治疗策略提供了巨大潜力。在这项多队列研究中，我们对1002名有临床注释的IBD患者和非IBD对照进行了广泛的多组学和多模态分析，纳入了正常和发炎肠道组织的全外显子组和RNA测序、血清蛋白质组学以及苏木精和伊红（H&E）染色组织切片图像的组织病理学评估。正常组织和发炎组织的转录组图谱揭示了克罗恩病（CD）和溃疡性结肠炎（UC）中不同的位点特异性炎症特征。利用血清蛋白质组学，我们开发了一种反映潜在肠道分子炎症的炎症蛋白严重程度特征。此外，基于基础模型的深度学习从H&E染色肠道组织切片图像中准确预测了组织学疾病活动评分，为临床评估提供了一个强大工具。我们的综合分析突出了结合多组学和先进计算方法以改善我们对IBD的理解和管理的潜力。
