{"title":"将注释信息纳入预测性 omic 研究的正则化 Cox 层次模型。","authors":"Dixin Shen, Juan Pablo Lewinger, Eric Kawaguchi","doi":"10.1186/s13040-024-00398-6","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Associated with high-dimensional omics data there are often \"meta-features\" such as biological pathways and functional annotations, summary statistics from similar studies that can be informative for predicting an outcome of interest. We introduce a regularized hierarchical framework for integrating meta-features, with the goal of improving prediction and feature selection performance with time-to-event outcomes.</p><p><strong>Methods: </strong>A hierarchical framework is deployed to incorporate meta-features. Regularization is applied to the omic features as well as the meta-features so that high-dimensional data can be handled at both levels. The proposed hierarchical Cox model can be efficiently fitted by a combination of iterative reweighted least squares and cyclic coordinate descent.</p><p><strong>Results: </strong>In a simulation study we show that when the external meta-features are informative, the regularized hierarchical model can substantially improve prediction performance over standard regularized Cox regression. We illustrate the proposed model with applications to breast cancer and melanoma survival based on gene expression profiles, which show the improvement in prediction performance by applying meta-features, as well as the discovery of important omic feature sets with sparse regularization at meta-feature level.</p><p><strong>Conclusions: </strong>The proposed hierarchical regularized regression model enables integration of external meta-feature information directly into the modeling process for time-to-event outcomes, improves prediction performance when the external meta-feature data is informative. Importantly, when the external meta-features are uninformative, the prediction performance based on the regularized hierarchical model is on par with standard regularized Cox regression, indicating robustness of the framework. In addition to developing predictive signatures, the model can also be deployed in discovery applications where the main goal is to identify important features associated with the outcome rather than developing a predictive model.</p>","PeriodicalId":48947,"journal":{"name":"Biodata Mining","volume":null,"pages":null},"PeriodicalIF":4.0000,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515443/pdf/","citationCount":"0","resultStr":"{\"title\":\"A regularized Cox hierarchical model for incorporating annotation information in predictive omic studies.\",\"authors\":\"Dixin Shen, Juan Pablo Lewinger, Eric Kawaguchi\",\"doi\":\"10.1186/s13040-024-00398-6\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Associated with high-dimensional omics data there are often \\\"meta-features\\\" such as biological pathways and functional annotations, summary statistics from similar studies that can be informative for predicting an outcome of interest. We introduce a regularized hierarchical framework for integrating meta-features, with the goal of improving prediction and feature selection performance with time-to-event outcomes.</p><p><strong>Methods: </strong>A hierarchical framework is deployed to incorporate meta-features. Regularization is applied to the omic features as well as the meta-features so that high-dimensional data can be handled at both levels. The proposed hierarchical Cox model can be efficiently fitted by a combination of iterative reweighted least squares and cyclic coordinate descent.</p><p><strong>Results: </strong>In a simulation study we show that when the external meta-features are informative, the regularized hierarchical model can substantially improve prediction performance over standard regularized Cox regression. We illustrate the proposed model with applications to breast cancer and melanoma survival based on gene expression profiles, which show the improvement in prediction performance by applying meta-features, as well as the discovery of important omic feature sets with sparse regularization at meta-feature level.</p><p><strong>Conclusions: </strong>The proposed hierarchical regularized regression model enables integration of external meta-feature information directly into the modeling process for time-to-event outcomes, improves prediction performance when the external meta-feature data is informative. Importantly, when the external meta-features are uninformative, the prediction performance based on the regularized hierarchical model is on par with standard regularized Cox regression, indicating robustness of the framework. In addition to developing predictive signatures, the model can also be deployed in discovery applications where the main goal is to identify important features associated with the outcome rather than developing a predictive model.</p>\",\"PeriodicalId\":48947,\"journal\":{\"name\":\"Biodata Mining\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.0000,\"publicationDate\":\"2024-10-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515443/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biodata Mining\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1186/s13040-024-00398-6\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MATHEMATICAL & COMPUTATIONAL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biodata Mining","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1186/s13040-024-00398-6","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MATHEMATICAL & COMPUTATIONAL BIOLOGY","Score":null,"Total":0}
A regularized Cox hierarchical model for incorporating annotation information in predictive omic studies.
Background: Associated with high-dimensional omics data there are often "meta-features" such as biological pathways and functional annotations, summary statistics from similar studies that can be informative for predicting an outcome of interest. We introduce a regularized hierarchical framework for integrating meta-features, with the goal of improving prediction and feature selection performance with time-to-event outcomes.
Methods: A hierarchical framework is deployed to incorporate meta-features. Regularization is applied to the omic features as well as the meta-features so that high-dimensional data can be handled at both levels. The proposed hierarchical Cox model can be efficiently fitted by a combination of iterative reweighted least squares and cyclic coordinate descent.
Results: In a simulation study we show that when the external meta-features are informative, the regularized hierarchical model can substantially improve prediction performance over standard regularized Cox regression. We illustrate the proposed model with applications to breast cancer and melanoma survival based on gene expression profiles, which show the improvement in prediction performance by applying meta-features, as well as the discovery of important omic feature sets with sparse regularization at meta-feature level.
Conclusions: The proposed hierarchical regularized regression model enables integration of external meta-feature information directly into the modeling process for time-to-event outcomes, improves prediction performance when the external meta-feature data is informative. Importantly, when the external meta-features are uninformative, the prediction performance based on the regularized hierarchical model is on par with standard regularized Cox regression, indicating robustness of the framework. In addition to developing predictive signatures, the model can also be deployed in discovery applications where the main goal is to identify important features associated with the outcome rather than developing a predictive model.
期刊介绍:
BioData Mining is an open access, open peer-reviewed journal encompassing research on all aspects of data mining applied to high-dimensional biological and biomedical data, focusing on computational aspects of knowledge discovery from large-scale genetic, transcriptomic, genomic, proteomic, and metabolomic data.
Topical areas include, but are not limited to:
-Development, evaluation, and application of novel data mining and machine learning algorithms.
-Adaptation, evaluation, and application of traditional data mining and machine learning algorithms.
-Open-source software for the application of data mining and machine learning algorithms.
-Design, development and integration of databases, software and web services for the storage, management, retrieval, and analysis of data from large scale studies.
-Pre-processing, post-processing, modeling, and interpretation of data mining and machine learning results for biological interpretation and knowledge discovery.