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利用“组学/数字病理学数据融合”预测乳腺癌的化疗敏感性。

Predicting chemoinsensitivity in breast cancer with 'omics/digital pathology data fusion.

机构信息

Systems Biology Centre, University of Warwick, Warwick, UK; Warwick Medical School, University of Warwick, Warwick, UK.

Division of Molecular Pathology , Centre for Evolution and Cancer, The Institute of Cancer Research , London, UK.

出版信息

R Soc Open Sci. 2016 Feb 10;3(2):140501. doi: 10.1098/rsos.140501. eCollection 2016 Feb.

Abstract

Predicting response to treatment and disease-specific deaths are key tasks in cancer research yet there is a lack of methodologies to achieve these. Large-scale 'omics and digital pathology technologies have led to the need for effective statistical methods for data fusion to extract the most useful patterns from these diverse data types. We present FusionGP, a method for combining heterogeneous data types designed specifically for predicting outcome of treatment and disease. FusionGP is a Gaussian process model that includes a generalization of feature selection for biomarker discovery, allowing for simultaneous, sparse feature selection across multiple data types. Importantly, it can accommodate highly nonlinear structure in the data, and automatically infers the optimal contribution from each input data type. FusionGP compares favourably to several popular classification methods, including the Random Forest classifier, a stepwise logistic regression model and the Support Vector Machine on single data types. By combining gene expression, copy number alteration and digital pathology image data in 119 estrogen receptor (ER)-negative and 345 ER-positive breast tumours, we aim to predict two important clinical outcomes: death and chemoinsensitivity. While gene expression data give the best predictive performance in the majority of cases, the digital pathology data are much better for predicting death in ER cases. Thus, FusionGP is a new tool for selecting informative features from heterogeneous data types and predicting treatment response and prognosis.

摘要

预测治疗反应和疾病特异性死亡是癌症研究的关键任务,但缺乏实现这些任务的方法。大规模的“组学”和数字病理学技术导致需要有效的统计方法来融合数据,以从这些不同类型的数据中提取最有用的模式。我们提出了 FusionGP,这是一种专门用于预测治疗结果和疾病的异构数据类型组合的方法。FusionGP 是一种高斯过程模型,包括用于生物标志物发现的特征选择的泛化,允许在多个数据类型中同时进行稀疏特征选择。重要的是,它可以适应数据中的高度非线性结构,并自动推断每个输入数据类型的最佳贡献。FusionGP 与几种流行的分类方法相比具有优势,包括随机森林分类器、逐步逻辑回归模型和支持向量机在单一数据类型上的表现。通过结合 119 例雌激素受体(ER)阴性和 345 例 ER 阳性乳腺癌中的基因表达、拷贝数改变和数字病理学图像数据,我们旨在预测两个重要的临床结果:死亡和化疗敏感性。虽然在大多数情况下,基因表达数据提供了最佳的预测性能,但数字病理学数据在预测 ER 病例的死亡方面要好得多。因此,FusionGP 是一种从异构数据类型中选择信息丰富的特征并预测治疗反应和预后的新工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91b2/4785962/5498a2c0956b/rsos140501-g1.jpg

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