Carmichael Iain, Calhoun Benjamin C, Hoadley Katherine A, Troester Melissa A, Geradts Joseph, Couture Heather D, Olsson Linnea, Perou Charles M, Niethammer Marc, Hannig Jan, Marron J S
University of Washington.
University of North Carolina at Chapel Hill.
Ann Appl Stat. 2021 Dec;15(4):1697-1722. doi: 10.1214/20-aoas1433. Epub 2021 Dec 21.
The two main approaches in the study of breast cancer are histopathology (analyzing visual characteristics of tumors) and genomics. While both histopathology and genomics are fundamental to cancer research, the connections between these fields have been relatively superficial. We bridge this gap by investigating the Carolina Breast Cancer Study through the development of an integrative, exploratory analysis framework. Our analysis gives insights - some known, some novel - that are engaging to both pathologists and geneticists. Our analysis framework is based on Angle-based Joint and Individual Variation Explained (AJIVE) for statistical data integration and exploits Convolutional Neural Networks (CNNs) as a powerful, automatic method for image feature extraction. CNNs raise interpretability issues that we address by developing novel methods to explore visual modes of variation captured by statistical algorithms (e.g. PCA or AJIVE) applied to CNN features.
乳腺癌研究中的两种主要方法是组织病理学(分析肿瘤的视觉特征)和基因组学。虽然组织病理学和基因组学对癌症研究都至关重要,但这些领域之间的联系相对较为表面。我们通过开发一个综合的探索性分析框架来研究卡罗来纳乳腺癌研究,从而弥合这一差距。我们的分析提供了一些见解——有些是已知的,有些是新颖的——这些见解对病理学家和遗传学家都很有吸引力。我们的分析框架基于用于统计数据整合的基于角度的联合和个体变异解释(AJIVE),并利用卷积神经网络(CNN)作为一种强大的自动图像特征提取方法。CNN引发了可解释性问题,我们通过开发新方法来探索应用于CNN特征的统计算法(如主成分分析或AJIVE)所捕获的视觉变异模式来解决这些问题。
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