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      Predicting clinical outcomes from large scale cancer genomic profiles with deep survival models

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          Abstract

          Translating the vast data generated by genomic platforms into accurate predictions of clinical outcomes is a fundamental challenge in genomic medicine. Many prediction methods face limitations in learning from the high-dimensional profiles generated by these platforms, and rely on experts to hand-select a small number of features for training prediction models. In this paper, we demonstrate how deep learning and Bayesian optimization methods that have been remarkably successful in general high-dimensional prediction tasks can be adapted to the problem of predicting cancer outcomes. We perform an extensive comparison of Bayesian optimized deep survival models and other state of the art machine learning methods for survival analysis, and describe a framework for interpreting deep survival models using a risk backpropagation technique. Finally, we illustrate that deep survival models can successfully transfer information across diseases to improve prognostic accuracy. We provide an open-source software implementation of this framework called SurvivalNet that enables automatic training, evaluation and interpretation of deep survival models.

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          Most cited references32

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          Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles

          Although genomewide RNA expression analysis has become a routine tool in biomedical research, extracting biological insight from such information remains a major challenge. Here, we describe a powerful analytical method called Gene Set Enrichment Analysis (GSEA) for interpreting gene expression data. The method derives its power by focusing on gene sets, that is, groups of genes that share common biological function, chromosomal location, or regulation. We demonstrate how GSEA yields insights into several cancer-related data sets, including leukemia and lung cancer. Notably, where single-gene analysis finds little similarity between two independent studies of patient survival in lung cancer, GSEA reveals many biological pathways in common. The GSEA method is embodied in a freely available software package, together with an initial database of 1,325 biologically defined gene sets.
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            Deep learning.

            Deep learning allows computational models that are composed of multiple processing layers to learn representations of data with multiple levels of abstraction. These methods have dramatically improved the state-of-the-art in speech recognition, visual object recognition, object detection and many other domains such as drug discovery and genomics. Deep learning discovers intricate structure in large data sets by using the backpropagation algorithm to indicate how a machine should change its internal parameters that are used to compute the representation in each layer from the representation in the previous layer. Deep convolutional nets have brought about breakthroughs in processing images, video, speech and audio, whereas recurrent nets have shone light on sequential data such as text and speech.
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              The Molecular Signatures Database (MSigDB) hallmark gene set collection.

              The Molecular Signatures Database (MSigDB) is one of the most widely used and comprehensive databases of gene sets for performing gene set enrichment analysis. Since its creation, MSigDB has grown beyond its roots in metabolic disease and cancer to include >10,000 gene sets. These better represent a wider range of biological processes and diseases, but the utility of the database is reduced by increased redundancy across, and heterogeneity within, gene sets. To address this challenge, here we use a combination of automated approaches and expert curation to develop a collection of "hallmark" gene sets as part of MSigDB. Each hallmark in this collection consists of a "refined" gene set, derived from multiple "founder" sets, that conveys a specific biological state or process and displays coherent expression. The hallmarks effectively summarize most of the relevant information of the original founder sets and, by reducing both variation and redundancy, provide more refined and concise inputs for gene set enrichment analysis.
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                Author and article information

                Contributors
                lee.cooper@emory.edu
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                15 September 2017
                15 September 2017
                2017
                : 7
                : 11707
                Affiliations
                [1 ]ISNI 0000 0001 0941 6502, GRID grid.189967.8, Department of Biomedical Informatics, Emory University School of Medicine, ; Atlanta, GA 30322 USA
                [2 ]ISNI 0000000419368729, GRID grid.21729.3f, Department of Biostatistics, Mailman School of Public Health, Columbia University, ; New York, NY 10032 USA
                [3 ]ISNI 0000 0001 0941 6502, GRID grid.189967.8, Department of Biomedical Engineering, Georgia Institute of Technology/Emory University School of Medicine, ; Atlanta, GA 30322 USA
                [4 ]ISNI 000000041936877X, GRID grid.5386.8, Department of Computer Science, Cornell University, ; Ithaca, NY 14850 USA
                [5 ]ISNI 0000 0001 0941 6502, GRID grid.189967.8, Department of Neurology, Emory University School of Medicine, ; Atlanta, GA 30322 USA
                [6 ]ISNI 0000 0001 0941 6502, GRID grid.189967.8, Emory University School of Medicine, ; Atlanta, GA 30322 USA
                [7 ]ISNI 0000 0001 0941 6502, GRID grid.189967.8, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, ; Atlanta, GA 30322 USA
                [8 ]ISNI 0000 0001 0941 6502, GRID grid.189967.8, Winship Cancer Institute, Emory University, ; Atlanta, GA 30322 USA
                Author information
                http://orcid.org/0000-0002-3504-4965
                Article
                11817
                10.1038/s41598-017-11817-6
                5601479
                28916782
                0872d309-6083-4e1d-bc77-dae826ccf19c
                © The Author(s) 2017

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 23 May 2017
                : 30 August 2017
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