Dataset Information

Robust selection of cancer survival signatures from high-throughput genomic data using two-fold subsampling.

ABSTRACT: Identifying relevant signatures for clinical patient outcome is a fundamental task in high-throughput studies. Signatures, composed of features such as mRNAs, miRNAs, SNPs or other molecular variables, are often non-overlapping, even though they have been identified from similar experiments considering samples with the same type of disease. The lack of a consensus is mostly due to the fact that sample sizes are far smaller than the numbers of candidate features to be considered, and therefore signature selection suffers from large variation. We propose a robust signature selection method that enhances the selection stability of penalized regression algorithms for predicting survival risk. Our method is based on an aggregation of multiple, possibly unstable, signatures obtained with the preconditioned lasso algorithm applied to random (internal) subsamples of a given cohort data, where the aggregated signature is shrunken by a simple thresholding strategy. The resulting method, RS-PL, is conceptually simple and easy to apply, relying on parameters automatically tuned by cross validation. Robust signature selection using RS-PL operates within an (external) subsampling framework to estimate the selection probabilities of features in multiple trials of RS-PL. These probabilities are used for identifying reliable features to be included in a signature. Our method was evaluated on microarray data sets from neuroblastoma, lung adenocarcinoma, and breast cancer patients, extracting robust and relevant signatures for predicting survival risk. Signatures obtained by our method achieved high prediction performance and robustness, consistently over the three data sets. Genes with high selection probability in our robust signatures have been reported as cancer-relevant. The ordering of predictor coefficients associated with signatures was well-preserved across multiple trials of RS-PL, demonstrating the capability of our method for identifying a transferable consensus signature. The software is available as an R package rsig at CRAN (http://cran.r-project.org).

SUBMITTER: Lee S

PROVIDER: S-EPMC4190101 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Robust selection of cancer survival signatures from high-throughput genomic data using two-fold subsampling.

Lee Sangkyun S Rahnenführer Jörg J Lang Michel M De Preter Katleen K Mestdagh Pieter P Koster Jan J Versteeg Rogier R Stallings Raymond L RL Varesio Luigi L Asgharzadeh Shahab S Schulte Johannes H JH Fielitz Kathrin K Schwermer Melanie M Morik Katharina K Schramm Alexander A

PloS one 20141008 10

Identifying relevant signatures for clinical patient outcome is a fundamental task in high-throughput studies. Signatures, composed of features such as mRNAs, miRNAs, SNPs or other molecular variables, are often non-overlapping, even though they have been identified from similar experiments considering samples with the same type of disease. The lack of a consensus is mostly due to the fact that sample sizes are far smaller than the numbers of candidate features to be considered, and therefore si ...[more]

PMID: 25295525

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Project description:BackgroundHepatocellular carcinoma (HCC) is one of the most common cancers. The discovery of specific genes severing as biomarkers is of paramount significance for cancer diagnosis and prognosis. The high-throughput omics data generated by the cancer genome atlas (TCGA) consortium provides a valuable resource for the discovery of HCC biomarker genes. Numerous methods have been proposed to select cancer biomarkers. However, these methods have not investigated the robustness of identification with different feature selection techniques.MethodsWe use six different recursive feature elimination methods to select the gene signiatures of HCC from TCGA liver cancer data. The genes shared in the six selected subsets are proposed as robust biomarkers. Akaike information criterion (AIC) is employed to explain the optimization process of feature selection, which provides a statistical interpretation for the feature selection in machine learning methods. And we use several methods to validate the screened biomarkers.ResultsIn this paper, we propose a robust method for discovering biomarker genes for HCC from gene expression data. Specifically, we implement recursive feature elimination cross-validation (RFE-CV) methods based on six different classication algorithms. The overlaps in the discovered gene sets via different methods are referred as the identified biomarkers. We give an interpretation of the feature selection process based on machine learning using AIC in statistics. Furthermore, the features selected by the backward logistic stepwise regression via AIC minimum theory are completely contained in the identified biomarkers. Through the classification results, the superiority of interpretable robust biomarker discovery method is verified.ConclusionsIt is found that overlaps among gene subsets contain different quantitative features selected by the RFE-CV of 6 classifiers. The AIC values in the model selection provide a theoretical foundation for the feature selection process of biomarker discovery via machine learning. What's more, genes containing in more optimally selected subsets make better biological sense and implication. The quality of feature selection is improved by the intersections of biomarkers selected from different classifiers. This is a general method suitable for screening biomarkers of complex diseases from high-throughput data.

Dataset Information

Robust selection of cancer survival signatures from high-throughput genomic data using two-fold subsampling.

Publications

Robust selection of cancer survival signatures from high-throughput genomic data using two-fold subsampling.

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