A strategy to incorporate prior knowledge into correlation network cutoff selection

Nature Communications, vol. 11, pp. 5153

Abstract

Correlation networks are frequently used to statistically extract biological interactions between omics markers. Network edge selection is typically based on the statistical significance of the correlation coefficients. This procedure, however, is not guaranteed to capture biological mechanisms. We here propose an alternative approach for network reconstruction: a cutoff selection algorithm that maximizes the overlap of the inferred network with available prior knowledge. We first evaluate the approach on IgG glycomics data, for which the biochemical pathway is known and well-characterized. Importantly, even in the case of incomplete or incorrect prior knowledge, the optimal network is close to the true optimum. We then demonstrate the generalizability of the approach with applications to untargeted metabolomics and transcriptomics data. For the transcriptomics case, we demonstrate that the optimized network is superior to statistical networks in systematically retrieving interactions that were not included in the biological reference used for optimization.

Authors 15

1. Elisa Benedetti

   Cornell University · Helmholtz Munich · Weill Cornell Medicine · Institute of Computational Biology

   Affiliation as printed

   Department of Physiology and Biophysics, Weill Cornell Medicine, Institute for Computational Biomedicine, Englander Institute for Precision Medicine, New York, NY, 10021, USA

   Institute of Computational Biology, Helmholtz Center Munich - German Research Center for Environmental Health, 85764, Neuherberg, Germany

2. Maja Pučić‐Baković

   Genos (Croatia)

   Affiliation as printed

   Genos Glycoscience Research Laboratory, 10000, Zagreb, Croatia

3. Toma Keser

   University of Zagreb

   Affiliation as printed

   Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000, Zagreb, Croatia

4. Nathalie Gerstner

   Helmholtz Munich · Max Planck Institute of Psychiatry · Institute of Computational Biology

   Affiliation as printed

   Institute of Computational Biology, Helmholtz Center Munich - German Research Center for Environmental Health, 85764, Neuherberg, Germany

   Max Planck Institute for Psychiatry, 80804, Munich, Germany

5. Mustafa Büyüközkan

   Cornell University · Helmholtz Munich · Weill Cornell Medicine · Institute of Computational Biology

   Affiliation as printed

   Department of Physiology and Biophysics, Weill Cornell Medicine, Institute for Computational Biomedicine, Englander Institute for Precision Medicine, New York, NY, 10021, USA

   Institute of Computational Biology, Helmholtz Center Munich - German Research Center for Environmental Health, 85764, Neuherberg, Germany

6. Tamara Štambuk

   Genos (Croatia)

   Affiliation as printed

   Genos Glycoscience Research Laboratory, 10000, Zagreb, Croatia

7. Maurice H. J. Selman Aachen

   Leiden University Medical Center

   Affiliation as printed

   Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands

8. Igor Rudan

   University of Edinburgh

   Affiliation as printed

   Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, EH8 9AG, Edinburgh, UK

9. Ozren Polašek

   Gen-info · University of Split

   Affiliation as printed

   Gen-info Ltd., 10000, Zagreb, Croatia

   University of Split School of Medicine, 21000, Split, Croatia

10. Caroline Hayward

    Institute of Genetics and Cancer · MRC Human Genetics Unit · University of Edinburgh

    Affiliation as printed

    Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, EH4 2XU, Edinburgh, UK

11. Hassen A. Al-Amin

    Weill Cornell Medical College in Qatar · Weill Cornell Medicine

    Affiliation as printed

    Department of Psychiatry, Weill Cornell Medicine in Qatar, Doha, Qatar

12. Karsten Suhre

    Weill Cornell Medical College in Qatar

    Affiliation as printed

    Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Education City, Doha, Qatar

13. Gabi Kastenmüller

    Helmholtz Munich · Institute of Computational Biology

    Affiliation as printed

    Institute of Computational Biology, Helmholtz Center Munich - German Research Center for Environmental Health, 85764, Neuherberg, Germany

14. Gordan Lauc

    University of Zagreb · Genos (Croatia)

    Affiliation as printed

    Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000, Zagreb, Croatia

    Genos Glycoscience Research Laboratory, 10000, Zagreb, Croatia

15. Jan Krumsiek corresponding

    Cornell University · Helmholtz Munich · Weill Cornell Medicine · Institute of Computational Biology

    Affiliation as printed

    Department of Physiology and Biophysics, Weill Cornell Medicine, Institute for Computational Biomedicine, Englander Institute for Precision Medicine, New York, NY, 10021, USA. jak2043@med.cornell.edu

    Institute of Computational Biology, Helmholtz Center Munich - German Research Center for Environmental Health, 85764, Neuherberg, Germany. jak2043@med.cornell.edu

    Department of Physiology and Biophysics, Weill Cornell Medicine, Institute for Computational Biomedicine, Englander Institute for Precision Medicine, New York, NY, 10021, USA

    Institute of Computational Biology, Helmholtz Center Munich - German Research Center for Environmental Health, 85764, Neuherberg, Germany