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Using structural controllability in detecting effective immune system elements against cancer cells
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  • Ali Ebrahimi,
  • Reihane Fayazi,
  • Shaghayegh Baradaran Ghavami,
  • Elahe Safari,
  • Samane Khoshbakht,
  • Mohadeseh Zarei Ghobadi,
  • Mohammad Mehdi Naghizadeh,
  • Ali Masoudi-Nejad
Ali Ebrahimi
University of Tehran Institute of Biochemistry and Biophysics
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Reihane Fayazi
Tarbiat Modares University Faculty of Medical Sciences
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Shaghayegh Baradaran Ghavami
Shahid Beheshti University of Medical Sciences Research Institute for Gastroenterology and Liver Diseases
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Elahe Safari
Iran University of Medical Sciences Nursing Care Research Center
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Samane Khoshbakht
University of Tehran Institute of Biochemistry and Biophysics
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Mohadeseh Zarei Ghobadi
University of Tehran Institute of Biochemistry and Biophysics
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Mohammad Mehdi Naghizadeh
University of Tehran Institute of Biochemistry and Biophysics
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Ali Masoudi-Nejad
University of Tehran Institute of Biochemistry and Biophysics

Corresponding Author:[email protected]

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Abstract

Motivation: Cancer, a leading cause of death worldwide, is intertwined with immune system. Changing the state of immune system, as a complex network of cells and molecules interacting in a hierarchical mode, holds considerable fascination to fight cancer. This alteration can involve debilitating pro-tumorigenic and reinvigorating anti-tumorigenic functions by the help of driver vertices. The utilization of network controllability and control centrality-based analysis will aid in the identification of driver vertices to control target proteins that play significant roles in the anti-tumorigenic and pro-tumorigenic functions of immune cells. In this study, a weighted generalization of the control centrality was constructed, in which the control power of each vertex in the network is obtained based on the importance of a set of under control vertices. Results: Screening all homo sapiens-related pathways in KEGG database, we find that “Immune and cancer pathways” subnetwork showed the greatest number of edges and nodes in relation to positive and negative target proteins. The first five driver vertices obtained for positive targets are ICAM2, TLR2, MAP2K4, ELK1, SIRT1 and for negative targets are ELK4, RBX1, NFATC1, NFATC2, NFATC3. Our results suggest that exposing the external signal to reinvigorate driver vertices of positive targets and debilitate driver vertices of negative target will result in changing the immune system state to fight cancer.
04 Sep 2023Submitted to Immunology
05 Sep 2023Submission Checks Completed
05 Sep 2023Assigned to Editor
05 Sep 2023Review(s) Completed, Editorial Evaluation Pending
06 Oct 2023Reviewer(s) Assigned