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The DNA walk and its demonstration of deterministic chaos-relevance to genomic alterations in lung cancer

Hewelt, Blake and Li, Haiqing and Jolly, Mohit Kumar and Kulkarni, Prakash and Mambetsariev, Ise and Salgia, Ravi (2019) The DNA walk and its demonstration of deterministic chaos-relevance to genomic alterations in lung cancer. In: BIOINFORMATICS, 35 (16). pp. 2738-2748.

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Official URL: http:/dx.doi.org/10.1093/bioinformatics/bty1021

Abstract

Motivation: Advancements in cancer genetics have facilitated the development of therapies with actionable mutations. Although mutated genes have been studied extensively, their chaotic behavior has not been appreciated. Thus, in contrast to naive DNA, mutated DNA sequences can display characteristics of unpredictability and sensitivity to the initial conditions that may be dictated by the environment, expression patterns and presence of other genomic alterations. Employing a DNA walk as a form of 2D analysis of the nucleotide sequence, we demonstrate that chaotic behavior in the sequence of a mutated gene can be predicted. Results: Using fractal analysis for these DNA walks, we have determined the complexity and nucleotide variance of commonly observed mutated genes in non-small cell lung cancer, and their wild-type counterparts. DNA walks for wild-type genes demonstrate varying levels of chaos, with BRAF, NTRK1 and MET exhibiting greater levels of chaos than KRAS, paxillin and EGFR. Analyzing changes in chaotic properties, such as changes in periodicity and linearity, reveal that while deletion mutations indicate a notable disruption in fractal `self-similarity', fusion mutations demonstrate bifurcations between the two genes. Our results suggest that the fractals generated by DNA walks can yield important insights into potential consequences of these mutated genes.

Item Type: Journal Article
Additional Information: Copyright of this article belongs to OXFORD UNIV PRESS
Keywords: KRAS MUTATIONS; EGFR; REPRESENTATION; TARGETS; MET
Department/Centre: Division of Interdisciplinary Research > Centre for Biosystems Science and Engineering
Depositing User: Id for Latest eprints
Date Deposited: 06 Dec 2019 11:18
Last Modified: 06 Dec 2019 11:18
URI: http://eprints.iisc.ac.in/id/eprint/63869

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