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The spike-and-slab lasso Cox model for survival prediction and associated genes detection.

ABSTRACT: Large-scale molecular profiling data have offered extraordinary opportunities to improve survival prediction of cancers and other diseases and to detect disease associated genes. However, there are considerable challenges in analyzing large-scale molecular data.We propose new Bayesian hierarchical Cox proportional hazards models, called the spike-and-slab lasso Cox, for predicting survival outcomes and detecting associated genes. We also develop an efficient algorithm to fit the proposed models by incorporating Expectation-Maximization steps into the extremely fast cyclic coordinate descent algorithm. The performance of the proposed method is assessed via extensive simulations and compared with the lasso Cox regression. We demonstrate the proposed procedure on two cancer datasets with censored survival outcomes and thousands of molecular features. Our analyses suggest that the proposed procedure can generate powerful prognostic models for predicting cancer survival and can detect associated genes.The methods have been implemented in a freely available R package BhGLM ( http://www.ssg.uab.edu/bhglm/ ).nyi@uab.edu.Supplementary data are available at Bioinformatics online.

SUBMITTER: Tang Z

PROVIDER: S-EPMC5870779 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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The spike-and-slab lasso Cox model for survival prediction and associated genes detection.

Tang Zaixiang Z Shen Yueping Y Zhang Xinyan X Yi Nengjun N

Bioinformatics (Oxford, England) 20170901 18

<h4>Motivation</h4>Large-scale molecular profiling data have offered extraordinary opportunities to improve survival prediction of cancers and other diseases and to detect disease associated genes. However, there are considerable challenges in analyzing large-scale molecular data.<h4>Results</h4>We propose new Bayesian hierarchical Cox proportional hazards models, called the spike-and-slab lasso Cox, for predicting survival outcomes and detecting associated genes. We also develop an efficient al ...[more]

PMID: 28472220

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Project description:BackgroundPan-omics, pan-cancer analysis has advanced our understanding of the molecular heterogeneity of cancer. However, such analyses have been limited in their ability to use information from multiple sources of data (e.g., omics platforms) and multiple sample sets (e.g., cancer types) to predict clinical outcomes. We address the issue of prediction across multiple high-dimensional sources of data and sample sets by using molecular patterns identified by BIDIFAC+, a method for integrative dimension reduction of bidimensionally-linked matrices, in a Bayesian hierarchical model. Our model performs variable selection through spike-and-slab priors that borrow information across clustered data. We use this model to predict overall patient survival from the Cancer Genome Atlas with data from 29 cancer types and 4 omics sources and use simulations to characterize the performance of the hierarchical spike-and-slab prior.ResultsWe found that molecular patterns shared across all or most cancers were largely not predictive of survival. However, our model selected patterns unique to subsets of cancers that differentiate clinical tumor subtypes with markedly different survival outcomes. Some of these subtypes were previously established, such as subtypes of uterine corpus endometrial carcinoma, while others may be novel, such as subtypes within a set of kidney carcinomas. Through simulations, we found that the hierarchical spike-and-slab prior performs best in terms of variable selection accuracy and predictive power when borrowing information is advantageous, but also offers competitive performance when it is not.ConclusionsWe address the issue of prediction across multiple sources of data by using results from BIDIFAC+ in a Bayesian hierarchical model for overall patient survival. By incorporating spike-and-slab priors that borrow information across cancers, we identified molecular patterns that distinguish clinical tumor subtypes within a single cancer and within a group of cancers. We also corroborate the flexibility and performance of using spike-and-slab priors as a Bayesian variable selection approach.

Project description:BackgroundHistorically, the Cox proportional hazard regression model has been the mainstay for survival analyses in oncologic research. The Cox proportional hazard regression model generally is used based on an assumption of linear association. However, it is likely that, in reality, there are many clinicopathologic features that exhibit a nonlinear association in biomedicine.ObjectiveThe purpose of this study was to compare the deep-learning neural network model and the Cox proportional hazard regression model in the prediction of survival in women with cervical cancer.Study designThis was a retrospective pilot study of consecutive cases of newly diagnosed stage I-IV cervical cancer from 2000-2014. A total of 40 features that included patient demographics, vital signs, laboratory test results, tumor characteristics, and treatment types were assessed for analysis and grouped into 3 feature sets. The deep-learning neural network model was compared with the Cox proportional hazard regression model and 3 other survival analysis models for progression-free survival and overall survival. Mean absolute error and concordance index were used to assess the performance of these 5 models.ResultsThere were 768 women included in the analysis. The median age was 49 years, and the majority were Hispanic (71.7%). The majority of tumors were squamous (75.3%) and stage I (48.7%). The median follow-up time was 40.2 months; there were 241 events for recurrence and progression and 170 deaths during the follow-up period. The deep-learning model showed promising results in the prediction of progression-free survival when compared with the Cox proportional hazard regression model (mean absolute error, 29.3 vs 316.2). The deep-learning model also outperformed all the other models, including the Cox proportional hazard regression model, for overall survival (mean absolute error, Cox proportional hazard regression vs deep-learning, 43.6 vs 30.7). The performance of the deep-learning model further improved when more features were included (concordance index for progression-free survival: 0.695 for 20 features, 0.787 for 36 features, and 0.795 for 40 features). There were 10 features for progression-free survival and 3 features for overall survival that demonstrated significance only in the deep-learning model, but not in the Cox proportional hazard regression model. There were no features for progression-free survival and 3 features for overall survival that demonstrated significance only in the Cox proportional hazard regression model, but not in the deep-learning model.ConclusionOur study suggests that the deep-learning neural network model may be a useful analytic tool for survival prediction in women with cervical cancer because it exhibited superior performance compared with the Cox proportional hazard regression model. This novel analytic approach may provide clinicians with meaningful survival information that potentially could be integrated into treatment decision-making and planning. Further validation studies are necessary to support this pilot study.

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The spike-and-slab lasso Cox model for survival prediction and associated genes detection.

Publications

The spike-and-slab lasso Cox model for survival prediction and associated genes detection.

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