Probabilistic pathway-based multimodal factor analysis
Bioinformatics, vol. 40, pp. i189–i198
Abstract
MOTIVATION: Multimodal profiling strategies promise to produce more informative insights into biomedical cohorts via the integration of the information each modality contributes. To perform this integration, however, the development of novel analytical strategies is needed. Multimodal profiling strategies often come at the expense of lower sample numbers, which can challenge methods to uncover shared signals across a cohort. Thus, factor analysis approaches are commonly used for the analysis of high-dimensional data in molecular biology, however, they typically do not yield representations that are directly interpretable, whereas many research questions often center around the analysis of pathways associated with specific observations. RESULTS: We develop PathFA, a novel approach for multimodal factor analysis over the space of pathways. PathFA produces integrative and interpretable views across multimodal profiling technologies, which allow for the derivation of concrete hypotheses. PathFA combines a pathway-learning approach with integrative multimodal capability under a Bayesian procedure that is efficient, hyper-parameter free, and able to automatically infer observation noise from the data. We demonstrate strong performance on small sample sizes within our simulation framework and on matched proteomics and transcriptomics profiles from real tumor samples taken from the Swiss Tumor Profiler consortium. On a subcohort of melanoma patients, PathFA recovers pathway activity that has been independently associated with poor outcome. We further demonstrate the ability of this approach to identify pathways associated with the presence of specific cell-types as well as tumor heterogeneity. Our results show that we capture known biology, making it well suited for analyzing multimodal sample cohorts. AVAILABILITY AND IMPLEMENTATION: The tool is implemented in python and available at https://github.com/ratschlab/path-fa.
Authors 91
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Alexander Immer corresponding
ETH Zurich · Max Planck Institute for Intelligent Systems
Affiliation as printed
Biomedical Informatics Group, Department of Computer Science, ETH Zurich , 8092 Zurich, Switzerland
Max Planck Institute for Intelligent Systems , 72076 Tübingen, Germany
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SIB Swiss Institute of Bioinformatics · ETH Zurich
Affiliation as printed
Biomedical Informatics Group, Department of Computer Science, ETH Zurich , 8092 Zurich, Switzerland
Swiss Institute of Bioinformatics , 1015 Lausanne, Switzerland
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University of Basel · University Hospital of Basel
Affiliation as printed
Ovarian Cancer Research, Department of Biomedicine, University Hospital Basel and University of Basel , 4031 Basel, Switzerland
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SIB Swiss Institute of Bioinformatics · ETH Zurich
Affiliation as printed
Biomedical Informatics Group, Department of Computer Science, ETH Zurich , 8092 Zurich, Switzerland
Swiss Institute of Bioinformatics , 1015 Lausanne, Switzerland
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SIB Swiss Institute of Bioinformatics · ETH Zurich
Affiliation as printed
Biomedical Informatics Group, Department of Computer Science, ETH Zurich , 8092 Zurich, Switzerland
Swiss Institute of Bioinformatics , 1015 Lausanne, Switzerland
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SIB Swiss Institute of Bioinformatics · ETH Zurich · Institute of Translational Medicine
Affiliation as printed
ETH PHRT Swiss Multi-Omics Center (SMOC) , 8093 Zurich, Switzerland
Institute of Translational Medicine, Department of Health Sciences and Technology, ETH Zurich , 8093 Zurich, Switzerland
Swiss Institute of Bioinformatics , 1015 Lausanne, Switzerland
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SIB Swiss Institute of Bioinformatics · ETH Zurich · Institute of Translational Medicine
Affiliation as printed
Institute of Translational Medicine, Department of Health Sciences and Technology, ETH Zurich , 8093 Zurich, Switzerland
Swiss Institute of Bioinformatics , 1015 Lausanne, Switzerland
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SIB Swiss Institute of Bioinformatics · ETH Zurich · Institute of Translational Medicine
Affiliation as printed
Institute of Translational Medicine, Department of Health Sciences and Technology, ETH Zurich , 8093 Zurich, Switzerland
Swiss Institute of Bioinformatics , 1015 Lausanne, Switzerland
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SIB Swiss Institute of Bioinformatics · ETH Zurich · Institute of Translational Medicine
Affiliation as printed
Institute of Translational Medicine, Department of Health Sciences and Technology, ETH Zurich, 8093 Zurich, Switzerland
Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland
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ETH Zurich · Essen University Hospital · Universitätsklinikum Aachen · University Hospital Cologne · RWTH Aachen University
Affiliation as printed
Biomedical Informatics Group, Department of Computer Science, ETH Zurich , 8092 Zurich, Switzerland
Cancer Research Center Cologne Essen, University Hospital Cologne , 50937 Cologne, Germany
Joint Research Center for Computational Biomedicine, University Hospital RWTH Aachen , 52074 Aachen, Germany
Biomedical Informatics Group, Department of Computer Science, ETH Zurich, 8092 Zurich, Switzerland
Cancer Research Center Cologne Essen, University Hospital Cologne, 50937 Cologne, Germany
ETH Zurich, Zurich, Switzerland
Joint Research Center for Computational Biomedicine, University Hospital RWTH Aachen, 52074 Aachen, Germany � Corresponding author. Biomedical Informatics Group, Department of Computer Science,
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SIB Swiss Institute of Bioinformatics · ETH Zurich
Affiliation as printed
Biomedical Informatics Group, Department of Computer Science, ETH Zurich, 8092 Zurich, Switzerland
Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland
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ETH Zurich · Essen University Hospital · Universitätsklinikum Aachen · University Hospital Cologne · RWTH Aachen University
Affiliation as printed
Biomedical Informatics Group, Department of Computer Science, ETH Zurich, 8092 Zurich, Switzerland
Cancer Research Center Cologne Essen, University Hospital Cologne, 50937 Cologne, Germany
ETH Zurich, Zurich, Switzerland
Joint Research Center for Computational Biomedicine, University Hospital RWTH Aachen, 52074 Aachen, Germany � Corresponding author. Biomedical Informatics Group, Department of Computer Science,
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SIB Swiss Institute of Bioinformatics · ETH Zurich
Affiliation as printed
Biomedical Informatics Group, Department of Computer Science, ETH Zurich, 8092 Zurich, Switzerland
Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland
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ETH Zurich · Max Planck Institute for Intelligent Systems
Affiliation as printed
Biomedical Informatics Group, Department of Computer Science, ETH Zurich, 8092 Zurich, Switzerland
Max Planck Institute for Intelligent Systems, 72076 T € ubingen, Germany
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Gunnar Rätsch corresponding
SIB Swiss Institute of Bioinformatics · ETH Zurich · University Hospital Zurich
Affiliation as printed
AI Center at ETH Zurich , 8092 Zurich, Switzerland
Biomedical Informatics Group, Department of Computer Science, ETH Zurich , 8092 Zurich, Switzerland
Biomedical Informatics Research, University Hospital Zurich , 8006 Zurich, Switzerland
Department of Biology, ETH Zurich , 8049 Zurich, Switzerland
Swiss Institute of Bioinformatics , 1015 Lausanne, Switzerland
Biomedical Informatics Group, Department of Computer Science, ETH Zurich, 8092 Zurich, Switzerland
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