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Slaying (Yet Again) the Brain-Eating Zombie Called the “Isochore Theory”: A Segmentation Algorithm Used to “Confirm” the Existence of Isochores Creates “Isochores” Where None Exist

The isochore theory, which was proposed more than 40 years ago, depicts the mammalian genome as a mosaic of long, homogeneous regions that are characterized by their guanine and cytosine (GC) content. The human genome, for instance, was claimed to consist of five compositionally distinct isochore fa...

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Autor principal: Graur, Dan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9224211/
https://www.ncbi.nlm.nih.gov/pubmed/35743002
http://dx.doi.org/10.3390/ijms23126558
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author Graur, Dan
author_facet Graur, Dan
author_sort Graur, Dan
collection PubMed
description The isochore theory, which was proposed more than 40 years ago, depicts the mammalian genome as a mosaic of long, homogeneous regions that are characterized by their guanine and cytosine (GC) content. The human genome, for instance, was claimed to consist of five compositionally distinct isochore families. The isochore theory, in all its reincarnations, has been repeatedly falsified in the literature, yet isochore proponents have persistently resurrected it by either redefining isochores or by proposing alternative means of testing the theory. Here, I deal with the latest attempt to salvage this seemingly immortal zombie—a sequence segmentation method called isoSegmenter, which was claimed to “identify” isochores while at the same time disregarding the main characteristic attribute of isochores—compositional homogeneity. I used a series of controlled, randomly generated simulated sequences as a benchmark to study the performance of isoSegmenter. The main advantage of using simulated sequences is that, unlike real data, the exact start and stop point of any isochore or homogeneous compositional domain is known. Based on three key performance metrics—sensitivity, precision, and Jaccard similarity index—isoSegmenter was found to be vastly inferior to isoPlotter, a segmentation algorithm with no user input. Moreover, isoSegmenter identified isochores where none exist and failed to identify compositionally homogeneous sequences that were shorter than 100−200 kb. Will this zillionth refutation of “isochores” ensure a final and permanent entombment of the isochore theory? This author is not holding his breath.
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spelling pubmed-92242112022-06-24 Slaying (Yet Again) the Brain-Eating Zombie Called the “Isochore Theory”: A Segmentation Algorithm Used to “Confirm” the Existence of Isochores Creates “Isochores” Where None Exist Graur, Dan Int J Mol Sci Article The isochore theory, which was proposed more than 40 years ago, depicts the mammalian genome as a mosaic of long, homogeneous regions that are characterized by their guanine and cytosine (GC) content. The human genome, for instance, was claimed to consist of five compositionally distinct isochore families. The isochore theory, in all its reincarnations, has been repeatedly falsified in the literature, yet isochore proponents have persistently resurrected it by either redefining isochores or by proposing alternative means of testing the theory. Here, I deal with the latest attempt to salvage this seemingly immortal zombie—a sequence segmentation method called isoSegmenter, which was claimed to “identify” isochores while at the same time disregarding the main characteristic attribute of isochores—compositional homogeneity. I used a series of controlled, randomly generated simulated sequences as a benchmark to study the performance of isoSegmenter. The main advantage of using simulated sequences is that, unlike real data, the exact start and stop point of any isochore or homogeneous compositional domain is known. Based on three key performance metrics—sensitivity, precision, and Jaccard similarity index—isoSegmenter was found to be vastly inferior to isoPlotter, a segmentation algorithm with no user input. Moreover, isoSegmenter identified isochores where none exist and failed to identify compositionally homogeneous sequences that were shorter than 100−200 kb. Will this zillionth refutation of “isochores” ensure a final and permanent entombment of the isochore theory? This author is not holding his breath. MDPI 2022-06-12 /pmc/articles/PMC9224211/ /pubmed/35743002 http://dx.doi.org/10.3390/ijms23126558 Text en © 2022 by the author. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Graur, Dan
Slaying (Yet Again) the Brain-Eating Zombie Called the “Isochore Theory”: A Segmentation Algorithm Used to “Confirm” the Existence of Isochores Creates “Isochores” Where None Exist
title Slaying (Yet Again) the Brain-Eating Zombie Called the “Isochore Theory”: A Segmentation Algorithm Used to “Confirm” the Existence of Isochores Creates “Isochores” Where None Exist
title_full Slaying (Yet Again) the Brain-Eating Zombie Called the “Isochore Theory”: A Segmentation Algorithm Used to “Confirm” the Existence of Isochores Creates “Isochores” Where None Exist
title_fullStr Slaying (Yet Again) the Brain-Eating Zombie Called the “Isochore Theory”: A Segmentation Algorithm Used to “Confirm” the Existence of Isochores Creates “Isochores” Where None Exist
title_full_unstemmed Slaying (Yet Again) the Brain-Eating Zombie Called the “Isochore Theory”: A Segmentation Algorithm Used to “Confirm” the Existence of Isochores Creates “Isochores” Where None Exist
title_short Slaying (Yet Again) the Brain-Eating Zombie Called the “Isochore Theory”: A Segmentation Algorithm Used to “Confirm” the Existence of Isochores Creates “Isochores” Where None Exist
title_sort slaying (yet again) the brain-eating zombie called the “isochore theory”: a segmentation algorithm used to “confirm” the existence of isochores creates “isochores” where none exist
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9224211/
https://www.ncbi.nlm.nih.gov/pubmed/35743002
http://dx.doi.org/10.3390/ijms23126558
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