A time-dependent explainable radiomic analysis from the multi-omic cohort of CPTAC-Pancreatic Ductal Adenocarcinoma

IF 4.9 2区 医学 Q1 COMPUTER SCIENCE, INTERDISCIPLINARY APPLICATIONS
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引用次数: 0

Abstract

Background and Objective

In Pancreatic Ductal Adenocarcinoma (PDA), multi-omic models are emerging to answer unmet clinical needs to derive novel quantitative prognostic factors. We realized a pipeline that relies on survival machine-learning (SML) classifiers and explainability based on patients’ follow-up (FU) to stratify prognosis from the public-available multi-omic datasets of the CPTAC-PDA project.

Materials and Methods

Analyzed datasets included tumor-annotated radiologic images, clinical, and mutational data. A feature selection was based on univariate (UV) and multivariate (MV) survival analyses according to Overall Survival (OS) and recurrence (REC). In this study, we considered seven multi-omic datasets and compared four SML classifiers: Cox, survival random forest, generalized boosted, and support vector machines (SVM). For each classifier, we assessed the concordance (C) index on the validation set. The best classifiers for the validation set on both OS and REC underwent explainability analyses using SurvSHAP(t), which extends SHapley Additive exPlanations (SHAP).

Results

According to OS, after UV and MV analyses we selected 18/37 and 10/37 multi-omic features, respectively. According to REC, based on UV and MV analyses we selected 10/35 and 5/35 determinants, respectively. Generally, SML classifiers including radiomics outperformed those modelled on clinical or mutational predictors. For OS, the Cox model encompassing radiomic, clinical, and mutational features reached 75 % of C index, outperforming other classifiers. On the other hand, for REC, the SVM model including only radiomics emerged as the best-performing, with 68 % of C index. For OS, SurvSHAP(t) identified the first order Median Gray Level (GL) intensities, the gender, the tumor grade, the Joint Energy GL Co-occurrence Matrix (GLCM), and the GLCM Informational Measures of Correlations of type 1 as the most important features. For REC, the first order Median GL intensities, the GL size zone matrix Small Area Low GL Emphasis, and first order variance of GL intensities emerged as the most discriminative.

Conclusions

In this work, radiomics showed the potential for improving patients’ risk stratification in PDA. Furthermore, a deeper understanding of how radiomics can contribute to prognosis in PDA was achieved with a time-dependent explainability of the top multi-omic predictors.
从 CPTAC-胰腺导管腺癌多基因组队列中得出的时间依赖性可解释放射基因组分析。
背景和目的:在胰腺导管腺癌(PDA)中,多组学模型正在兴起,以满足尚未得到满足的临床需求,从而得出新的定量预后因素。我们利用生存机器学习(SML)分类器和基于患者随访(FU)的可解释性实现了一个管道,从 CPTAC-PDA 项目的公开多组学数据集中对预后进行分层:分析数据集包括肿瘤注释放射影像、临床和突变数据。根据总生存期(OS)和复发率(REC)进行单变量(UV)和多变量(MV)生存分析,选择特征。在这项研究中,我们考虑了七个多组数据集,并比较了四种 SML 分类器:Cox、生存随机森林、广义提升和支持向量机(SVM)。我们评估了每个分类器在验证集上的一致性(C)指数。使用SurvSHAP(t)对OS和REC验证集的最佳分类器进行了可解释性分析,SurvSHAP(t)扩展了SHapley Additive exPlanations(SHAP):根据 OS,经过 UV 和 MV 分析,我们分别选出了 18/37 和 10/37 个多原子特征。根据 REC,基于 UV 和 MV 分析,我们分别选择了 10/35 和 5/35 个决定因素。一般来说,包含放射组学的 SML 分类器优于以临床或突变预测因子为模型的分类器。就OS而言,包含放射组学、临床和突变特征的Cox模型达到了75%的C指数,优于其他分类器。另一方面,对于 REC,仅包含放射组学特征的 SVM 模型表现最佳,C 指数为 68%。对于 OS,SurvSHAP(t) 将一阶灰度级(GL)强度中值、性别、肿瘤分级、联合能量 GL 共现矩阵(GLCM)和 1 型 GLCM 相关信息度量确定为最重要的特征。就 REC 而言,一阶 GL 强度中位数、GL 大小区矩阵小区域低 GL 强调度和 GL 强度一阶方差成为最具鉴别力的特征:在这项工作中,放射组学显示出改善 PDA 患者风险分层的潜力。结论:这项研究表明,放射组学具有改善 PDA 患者风险分层的潜力。此外,通过对顶级多组学预测因子的时间依赖性解释,我们对放射组学如何有助于 PDA 的预后有了更深入的了解。
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来源期刊
Computer methods and programs in biomedicine
Computer methods and programs in biomedicine 工程技术-工程:生物医学
CiteScore
12.30
自引率
6.60%
发文量
601
审稿时长
135 days
期刊介绍: To encourage the development of formal computing methods, and their application in biomedical research and medical practice, by illustration of fundamental principles in biomedical informatics research; to stimulate basic research into application software design; to report the state of research of biomedical information processing projects; to report new computer methodologies applied in biomedical areas; the eventual distribution of demonstrable software to avoid duplication of effort; to provide a forum for discussion and improvement of existing software; to optimize contact between national organizations and regional user groups by promoting an international exchange of information on formal methods, standards and software in biomedicine. Computer Methods and Programs in Biomedicine covers computing methodology and software systems derived from computing science for implementation in all aspects of biomedical research and medical practice. It is designed to serve: biochemists; biologists; geneticists; immunologists; neuroscientists; pharmacologists; toxicologists; clinicians; epidemiologists; psychiatrists; psychologists; cardiologists; chemists; (radio)physicists; computer scientists; programmers and systems analysts; biomedical, clinical, electrical and other engineers; teachers of medical informatics and users of educational software.
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