Evaluation of the Efficacy of Cancer Drugs by Using the Second Largest Eigenvalue of Metabolic Cancer Pathways

Tomić, Draško; Skala, Karolj; Kranjčevic, Lado; Pirkić, Boris; Štifter, Sanja; Šmit, Iva (2018) Evaluation of the Efficacy of Cancer Drugs by Using the Second Largest Eigenvalue of Metabolic Cancer Pathways. Journal of Computer Science&Systems Biology, 11 (3). pp. 240-248. ISSN 0974-7230

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Abstract

Cancer is a system with thousands of genes and proteins with the complex interactions between them. By examining the cancer drug activity on only part of this system, we do not know in which direction the whole system will evolve, and whether therapy will be useful or not. This is one of the main reasons why cancer therapies still do not meet our expectations. In order to find more effective anticancer therapies, it is important to consider the impact of drugs on the entire cancer system. The second largest eigenvalue plays a key role in complex systems optimization. The algorithms minimizing the second largest eigenvalue of graphs have been already used to speed up processes in computer networks and differential cryptanalysis. Based on the aforementioned, it could be assumed that maximizing the second highest eigenvalue could slow down the processes in metabolic networks that describe processes in cancer. To verify our hypothesis, we have built the in silico model of cancer Vini and run it on a supercomputer. Vini transformed the metabolic pathways of cancer from Kyoto Encyclopedia of Genes and Genomes into the binding energy matrices representing binding energies between the genes and proteins on one side and drugs being investigated on another side. Some matrix elements also represent interactions between proteins and genes. Then, it calculated the second largest eigenvalues of these matrices. In the end, we compared the calculated results against the existing in vitro and in vivo experimental results. The calculated efficacy of cancer drugs was confirmed in 79.31% of in vivo experimental cases, and in 92.30% of in vitro experimental cases. These results show that the second largest eigenvalue plays an important role in metabolic cancer networks and that the Vini model can be an effective aid in finding more effective cancer therapies.

Item Type:	Article
Uncontrolled Keywords:	Graph eigenvalue ; Complex systems optimization ; Metabolic cancer networks ; Supercomputer ; Binding energy matrices
Subjects:	NATURAL SCIENCES > Mathematics
Divisions:	Center for Informatics and Computing
Depositing User:	Karolj Skala
Date Deposited:	02 Oct 2019 09:41
URI:	http://fulir.irb.hr/id/eprint/5018
DOI:	10.4172/jcsb.1000280

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