Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Causal integration of multi-omics data with prior knowledge to generate mechanistic hypotheses

View ORCID ProfileAurelien Dugourd, View ORCID ProfileChristoph Kuppe, View ORCID ProfileMarco Sciacovelli, View ORCID ProfileEnio Gjerga, View ORCID ProfileKristina B. Emdal, View ORCID ProfileDorte B. Bekker-Jensen, View ORCID ProfileJennifer Kranz, View ORCID ProfileEric. M. J. Bindels, Ana S. H. Costa, View ORCID ProfileJesper V. Olsen, View ORCID ProfileChristian Frezza, View ORCID ProfileRafael Kramann, View ORCID ProfileJulio Saez-Rodriguez
doi: https://doi.org/10.1101/2020.04.23.057893
Aurelien Dugourd
1Heidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, Bioquant, Heidelberg, Germany
2RWTH Aachen University, Faculty of Medicine, Joint Research Centre for Computational Biomedicine (JRC-COMBINE), 52074, Aachen, Germany
3Division of Nephrology and Clinical Immunology, Faculty of Medicine, RWTH Aachen University, Aachen, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Aurelien Dugourd
Christoph Kuppe
3Division of Nephrology and Clinical Immunology, Faculty of Medicine, RWTH Aachen University, Aachen, Germany
7Department of Urology and Kidney Transplantation, Martin Luther University, Halle (Saale), Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Christoph Kuppe
Marco Sciacovelli
4MRC Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre, Cambridge, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Marco Sciacovelli
Enio Gjerga
1Heidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, Bioquant, Heidelberg, Germany
2RWTH Aachen University, Faculty of Medicine, Joint Research Centre for Computational Biomedicine (JRC-COMBINE), 52074, Aachen, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Enio Gjerga
Kristina B. Emdal
5Proteomics Program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Kristina B. Emdal
Dorte B. Bekker-Jensen
5Proteomics Program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Dorte B. Bekker-Jensen
Jennifer Kranz
6Department of Urology and Pediatric Urology, St. Antonius Hospital Eschweiler, Academic Teaching Hospital of RWTH Aachen, Eschweiler, Germany
7Department of Urology and Kidney Transplantation, Martin Luther University, Halle (Saale), Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Jennifer Kranz
Eric. M. J. Bindels
8Department of Hematology, Erasmus MC, Rotterdam, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Eric. M. J. Bindels
Ana S. H. Costa
9Cold Spring Harbor Laboratory, One Bungtown Road, Cold Spring Harbor, NY 11724, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jesper V. Olsen
5Proteomics Program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Jesper V. Olsen
Christian Frezza
4MRC Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre, Cambridge, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Christian Frezza
  • For correspondence: julio.saez@bioquant.uni-heidelberg.de rkramann@ukaachen.de cf366@mrc-cu.cam.ac.uk
Rafael Kramann
3Division of Nephrology and Clinical Immunology, Faculty of Medicine, RWTH Aachen University, Aachen, Germany
10Department of Internal Medicine, Nephrology and Transplantation, Erasmus Medical Center, Rotterdam, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Rafael Kramann
  • For correspondence: julio.saez@bioquant.uni-heidelberg.de rkramann@ukaachen.de cf366@mrc-cu.cam.ac.uk
Julio Saez-Rodriguez
1Heidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, Bioquant, Heidelberg, Germany
2RWTH Aachen University, Faculty of Medicine, Joint Research Centre for Computational Biomedicine (JRC-COMBINE), 52074, Aachen, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Julio Saez-Rodriguez
  • For correspondence: julio.saez@bioquant.uni-heidelberg.de rkramann@ukaachen.de cf366@mrc-cu.cam.ac.uk
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Data/Code
  • Preview PDF
Loading

Abstract

Multi-omics datasets can provide molecular insights beyond the sum of individual omics. Diverse tools have been recently developed to integrate such datasets, but there are limited strategies to systematically extract mechanistic hypotheses from them. Here, we present COSMOS (Causal Oriented Search of Multi-Omics Space), a method that integrates phosphoproteomics, transcriptomics, and metabolics datasets. COSMOS combines extensive prior knowledge of signaling, metabolic, and gene regulatory networks with computational methods to estimate activities of transcription factors and kinases as well as network-level causal reasoning. COSMOS provides mechanistic hypotheses for experimental observations across multi-omics datasets. We applied COSMOS to a dataset comprising transcriptomics, phosphoproteomics, and metabolomics data from healthy and cancerous tissue from nine renal cell carcinoma patients. We used COSMOS to generate novel hypotheses such as the impact of Androgen Receptor on nucleoside metabolism and the influence of the JAK-STAT pathway on propionyl coenzyme A production. We expect that our freely available method will be broadly useful to extract mechanistic insights from multi-omics studies.

Figure
  • Download figure
  • Open in new tab

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • https://github.com/saezlab/COSMOS

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
Back to top
PreviousNext
Posted April 25, 2020.
Download PDF

Supplementary Material

Data/Code
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Causal integration of multi-omics data with prior knowledge to generate mechanistic hypotheses
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Causal integration of multi-omics data with prior knowledge to generate mechanistic hypotheses
Aurelien Dugourd, Christoph Kuppe, Marco Sciacovelli, Enio Gjerga, Kristina B. Emdal, Dorte B. Bekker-Jensen, Jennifer Kranz, Eric. M. J. Bindels, Ana S. H. Costa, Jesper V. Olsen, Christian Frezza, Rafael Kramann, Julio Saez-Rodriguez
bioRxiv 2020.04.23.057893; doi: https://doi.org/10.1101/2020.04.23.057893
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Causal integration of multi-omics data with prior knowledge to generate mechanistic hypotheses
Aurelien Dugourd, Christoph Kuppe, Marco Sciacovelli, Enio Gjerga, Kristina B. Emdal, Dorte B. Bekker-Jensen, Jennifer Kranz, Eric. M. J. Bindels, Ana S. H. Costa, Jesper V. Olsen, Christian Frezza, Rafael Kramann, Julio Saez-Rodriguez
bioRxiv 2020.04.23.057893; doi: https://doi.org/10.1101/2020.04.23.057893

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Bioinformatics
Subject Areas
All Articles
  • Animal Behavior and Cognition (3512)
  • Biochemistry (7352)
  • Bioengineering (5329)
  • Bioinformatics (20277)
  • Biophysics (10026)
  • Cancer Biology (7749)
  • Cell Biology (11319)
  • Clinical Trials (138)
  • Developmental Biology (6440)
  • Ecology (9958)
  • Epidemiology (2065)
  • Evolutionary Biology (13336)
  • Genetics (9362)
  • Genomics (12592)
  • Immunology (7714)
  • Microbiology (19045)
  • Molecular Biology (7447)
  • Neuroscience (41063)
  • Paleontology (300)
  • Pathology (1231)
  • Pharmacology and Toxicology (2139)
  • Physiology (3164)
  • Plant Biology (6866)
  • Scientific Communication and Education (1274)
  • Synthetic Biology (1898)
  • Systems Biology (5318)
  • Zoology (1089)