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

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 naïve DNA, mutated DNA sequences can display characteristic...

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Autores principales: Hewelt, Blake, Li, Haiqing, Jolly, Mohit Kumar, Kulkarni, Prakash, Mambetsariev, Isa, Salgia, Ravi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6691335/
https://www.ncbi.nlm.nih.gov/pubmed/30615123
http://dx.doi.org/10.1093/bioinformatics/bty1021
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author Hewelt, Blake
Li, Haiqing
Jolly, Mohit Kumar
Kulkarni, Prakash
Mambetsariev, Isa
Salgia, Ravi
author_facet Hewelt, Blake
Li, Haiqing
Jolly, Mohit Kumar
Kulkarni, Prakash
Mambetsariev, Isa
Salgia, Ravi
author_sort Hewelt, Blake
collection PubMed
description 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 naïve 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. AVAILABILITY AND IMPLEMENTATION: Introduction to Turtle graphics in Python is an open source article on learning to develop a script for Turtle graphics in Python, freely available on the web at https://docs.python.org/2/library/turtle.html. cDNA sequences were obtained through NCBI RefSeq database, an open source database that contains information on a large array of genes, such as their nucleotide and amino acid sequences, freely available at https://www.ncbi.nlm.nih.gov/refseq/. FracLac plugin for Fractal analysis in ImageJ is an open source plugin for the ImageJ program to perform fractal analysis, free to download at https://imagej.nih.gov/ij/plugins/fraclac/FLHelp/Introduction.html. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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spelling pubmed-66913352019-08-16 The DNA walk and its demonstration of deterministic chaos—relevance to genomic alterations in lung cancer Hewelt, Blake Li, Haiqing Jolly, Mohit Kumar Kulkarni, Prakash Mambetsariev, Isa Salgia, Ravi Bioinformatics Original Papers 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 naïve 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. AVAILABILITY AND IMPLEMENTATION: Introduction to Turtle graphics in Python is an open source article on learning to develop a script for Turtle graphics in Python, freely available on the web at https://docs.python.org/2/library/turtle.html. cDNA sequences were obtained through NCBI RefSeq database, an open source database that contains information on a large array of genes, such as their nucleotide and amino acid sequences, freely available at https://www.ncbi.nlm.nih.gov/refseq/. FracLac plugin for Fractal analysis in ImageJ is an open source plugin for the ImageJ program to perform fractal analysis, free to download at https://imagej.nih.gov/ij/plugins/fraclac/FLHelp/Introduction.html. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. Oxford University Press 2019-08-15 2019-01-07 /pmc/articles/PMC6691335/ /pubmed/30615123 http://dx.doi.org/10.1093/bioinformatics/bty1021 Text en © The Author(s) 2019. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Original Papers
Hewelt, Blake
Li, Haiqing
Jolly, Mohit Kumar
Kulkarni, Prakash
Mambetsariev, Isa
Salgia, Ravi
The DNA walk and its demonstration of deterministic chaos—relevance to genomic alterations in lung cancer
title The DNA walk and its demonstration of deterministic chaos—relevance to genomic alterations in lung cancer
title_full The DNA walk and its demonstration of deterministic chaos—relevance to genomic alterations in lung cancer
title_fullStr The DNA walk and its demonstration of deterministic chaos—relevance to genomic alterations in lung cancer
title_full_unstemmed The DNA walk and its demonstration of deterministic chaos—relevance to genomic alterations in lung cancer
title_short The DNA walk and its demonstration of deterministic chaos—relevance to genomic alterations in lung cancer
title_sort dna walk and its demonstration of deterministic chaos—relevance to genomic alterations in lung cancer
topic Original Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6691335/
https://www.ncbi.nlm.nih.gov/pubmed/30615123
http://dx.doi.org/10.1093/bioinformatics/bty1021
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