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Rashmi Prasad

Rashmi Prasad

Assistant researcher

Rashmi Prasad

Robustness and lethality in multilayer biological molecular networks

Author

  • Xueming Liu
  • Enrico Maiorino
  • Arda Halu
  • Kimberly Glass
  • Rashmi B. Prasad
  • Joseph Loscalzo
  • Jianxi Gao
  • Amitabh Sharma

Summary, in English

Robustness is a prominent feature of most biological systems. Most previous related studies have been focused on homogeneous molecular networks. Here we propose a comprehensive framework for understanding how the interactions between genes, proteins and metabolites contribute to the determinants of robustness in a heterogeneous biological network. We integrate heterogeneous sources of data to construct a multilayer interaction network composed of a gene regulatory layer, a protein–protein interaction layer, and a metabolic layer. We design a simulated perturbation process to characterize the contribution of each gene to the overall system’s robustness, and find that influential genes are enriched in essential and cancer genes. We show that the proposed mechanism predicts a higher vulnerability of the metabolic layer to perturbations applied to genes associated with metabolic diseases. Furthermore, we find that the real network is comparably or more robust than expected in multiple random realizations. Finally, we analytically derive the expected robustness of multilayer biological networks starting from the degree distributions within and between layers. These results provide insights into the non-trivial dynamics occurring in the cell after a genetic perturbation is applied, confirming the importance of including the coupling between different layers of interaction in models of complex biological systems.

Department/s

  • Genomics, Diabetes and Endocrinology
  • EXODIAB: Excellence in Diabetes Research in Sweden

Publishing year

2020

Language

English

Publication/Series

Nature Communications

Volume

11

Issue

1

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Cell and Molecular Biology
  • Medical Genetics

Status

Published

Research group

  • Genomics, Diabetes and Endocrinology

ISBN/ISSN/Other

  • ISSN: 2041-1723