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Path2Omics:通过肿瘤组织病理学提高转录组学和甲基化预测准确性

Path2Omics: Enhanced transcriptomic and methylation prediction accuracy from tumor histopathology.

作者信息

Hoang Danh-Tai, Shulman Eldad D, Dhruba Saugato Rahman, Nair Nishanth Ulhas, Barman Ranjan K, Lalchungnunga H, Singh Omkar, Nasrallah MacLean P, Stone Eric A, Aldape Kenneth, Ruppin Eytan

出版信息

bioRxiv. 2025 Mar 16:2025.02.26.640189. doi: 10.1101/2025.02.26.640189.


DOI:10.1101/2025.02.26.640189
PMID:40568160
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12190742/
Abstract

UNLABELLED: Precision oncology is becoming increasingly integral to clinical practice, demonstrating notable improvements in treatment outcomes. While molecular data provide comprehensive insights, obtaining such data remains costly and time-consuming. To address this challenge, we developed Path2Omics, a deep learning model that predicts gene expression and methylation from histopathology for 23 cancer types. Path2Omics was trained on 20,497 slides (9,456 formalin-fixed and paraffin-embedded (FFPE) and 11,041 fresh frozen (FF)) from 8,007 patients across 23 The Cancer Genome Atlas cohorts. When tested on FFPE slides, the most readily available format in clinical pathology practice, the integrated model outperformed its individual FF and FFPE components, robustly predicting nearly 5,000 genes on average, approximately five times more than our recently published DeepPT model. Externally evaluated on seven independent cohorts, Path2Omics robustly predicted the expression of approximately 4,400 genes, yielding a 30% increase over the FFPE model alone. Finally, we demonstrate that the inferred gene expression is nearly as effective as the actual values in predicting patient survival and treatment response. These results lay the basis for using Path2Omics to advance precision oncology from histopathology slides in a speedy and cost-effective manner. STATEMENT OF SIGNIFICANCE: Path2Omics is a deep learning model that accurately predicts gene expression and methylation from histopathology slides across 23 cancer types. Unlike existing approaches that rely solely on FFPE slides for training, Path2Omics leverages both FFPE and FF slides by constructing two separate models and integrating them. Downstream analyses show that the inferred values from Path2Omics are nearly as effective as actual values in predicting patient survival and treatment response.

摘要

未标注:精准肿瘤学在临床实践中变得越来越不可或缺,治疗效果有了显著改善。虽然分子数据能提供全面的见解,但获取此类数据仍然成本高昂且耗时。为应对这一挑战,我们开发了Path2Omics,这是一种深度学习模型,可从23种癌症类型的组织病理学预测基因表达和甲基化。Path2Omics在来自23个癌症基因组图谱队列的8007名患者的20497张切片(9456张福尔马林固定石蜡包埋(FFPE)切片和11041张新鲜冷冻(FF)切片)上进行训练。当在临床病理学实践中最容易获得的FFPE切片上进行测试时,该集成模型优于其单独的FF和FFPE组件,平均能可靠地预测近5000个基因,大约是我们最近发表的DeepPT模型的五倍。在七个独立队列上进行外部评估时,Path2Omics可靠地预测了约4400个基因的表达,比单独的FFPE模型提高了30%。最后,我们证明推断的基因表达在预测患者生存和治疗反应方面几乎与实际值一样有效。这些结果为使用Path2Omics以快速且经济高效的方式从组织病理学切片推进精准肿瘤学奠定了基础。 意义声明:Path2Omics是一种深度学习模型,可准确地从23种癌症类型的组织病理学切片预测基因表达和甲基化。与现有仅依赖FFPE切片进行训练的方法不同,Path2Omics通过构建两个单独的模型并将它们集成,利用了FFPE和FF切片。下游分析表明,Path2Omics推断的值在预测患者生存和治疗反应方面几乎与实际值一样有效。

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