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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2019
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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. |
format | Online Article Text |
id | pubmed-6691335 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
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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