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Integration of gene co-expression analysis and multi-class SVM specifies the functional players involved in determining the fate of HTLV-1 infection toward the development of cancer (ATLL) or neurological disorder (HAM/TSP)

Human T-cell Leukemia Virus type-1 (HTLV-1) is an oncovirus that may cause two main life-threatening diseases including a cancer type named Adult T-cell Leukemia/Lymphoma (ATLL) and a neurological and immune disturbance known as HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP). Ho...

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Autores principales: Zarei Ghobadi, Mohadeseh, Emamzadeh, Rahman
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8765610/
https://www.ncbi.nlm.nih.gov/pubmed/35041720
http://dx.doi.org/10.1371/journal.pone.0262739
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author Zarei Ghobadi, Mohadeseh
Emamzadeh, Rahman
author_facet Zarei Ghobadi, Mohadeseh
Emamzadeh, Rahman
author_sort Zarei Ghobadi, Mohadeseh
collection PubMed
description Human T-cell Leukemia Virus type-1 (HTLV-1) is an oncovirus that may cause two main life-threatening diseases including a cancer type named Adult T-cell Leukemia/Lymphoma (ATLL) and a neurological and immune disturbance known as HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP). However, a large number of the infected subjects remain as asymptomatic carriers (ACs). There is no comprehensive study that determines which dysregulated genes differentiate the pathogenesis routes toward ATLL or HAM/TSP. Therefore, two main algorithms including weighted gene co-expression analysis (WGCNA) and multi-class support vector machines (SVM) were utilized to find major gene players in each condition. WGCNA was used to find the highly co-regulated genes and multi-class SVM was employed to identify the most important classifier genes. The identified modules from WGCNA were validated in the external datasets. Furthermore, to find specific modules for ATLL and HAM/TSP, the non-preserved modules in another condition were found. In the next step, a model was constructed by multi-class SVM. The results revealed 467, 3249, and 716 classifiers for ACs, ATLL, and HAM/TSP, respectively. Eventually, the common genes between the WGCNA results and classifier genes resulted from multi-class SVM that also determined as differentially expressed genes, were identified. Through these step-wise analyses, PAIP1, BCAS2, COPS2, CTNNB1, FASLG, GTPBP1, HNRNPA1, RBBP6, TOP1, SLC9A1, JMY, PABPC3, and PBX1 were found as the possible critical genes involved in the progression of ATLL. Moreover, FBXO9, ZNF526, ERCC8, WDR5, and XRCC3 were identified as the conceivable major involved genes in the development of HAM/TSP. These genes can be proposed as specific biomarker candidates and therapeutic targets for each disease.
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spelling pubmed-87656102022-01-19 Integration of gene co-expression analysis and multi-class SVM specifies the functional players involved in determining the fate of HTLV-1 infection toward the development of cancer (ATLL) or neurological disorder (HAM/TSP) Zarei Ghobadi, Mohadeseh Emamzadeh, Rahman PLoS One Research Article Human T-cell Leukemia Virus type-1 (HTLV-1) is an oncovirus that may cause two main life-threatening diseases including a cancer type named Adult T-cell Leukemia/Lymphoma (ATLL) and a neurological and immune disturbance known as HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP). However, a large number of the infected subjects remain as asymptomatic carriers (ACs). There is no comprehensive study that determines which dysregulated genes differentiate the pathogenesis routes toward ATLL or HAM/TSP. Therefore, two main algorithms including weighted gene co-expression analysis (WGCNA) and multi-class support vector machines (SVM) were utilized to find major gene players in each condition. WGCNA was used to find the highly co-regulated genes and multi-class SVM was employed to identify the most important classifier genes. The identified modules from WGCNA were validated in the external datasets. Furthermore, to find specific modules for ATLL and HAM/TSP, the non-preserved modules in another condition were found. In the next step, a model was constructed by multi-class SVM. The results revealed 467, 3249, and 716 classifiers for ACs, ATLL, and HAM/TSP, respectively. Eventually, the common genes between the WGCNA results and classifier genes resulted from multi-class SVM that also determined as differentially expressed genes, were identified. Through these step-wise analyses, PAIP1, BCAS2, COPS2, CTNNB1, FASLG, GTPBP1, HNRNPA1, RBBP6, TOP1, SLC9A1, JMY, PABPC3, and PBX1 were found as the possible critical genes involved in the progression of ATLL. Moreover, FBXO9, ZNF526, ERCC8, WDR5, and XRCC3 were identified as the conceivable major involved genes in the development of HAM/TSP. These genes can be proposed as specific biomarker candidates and therapeutic targets for each disease. Public Library of Science 2022-01-18 /pmc/articles/PMC8765610/ /pubmed/35041720 http://dx.doi.org/10.1371/journal.pone.0262739 Text en © 2022 Zarei Ghobadi, Emamzadeh https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Zarei Ghobadi, Mohadeseh
Emamzadeh, Rahman
Integration of gene co-expression analysis and multi-class SVM specifies the functional players involved in determining the fate of HTLV-1 infection toward the development of cancer (ATLL) or neurological disorder (HAM/TSP)
title Integration of gene co-expression analysis and multi-class SVM specifies the functional players involved in determining the fate of HTLV-1 infection toward the development of cancer (ATLL) or neurological disorder (HAM/TSP)
title_full Integration of gene co-expression analysis and multi-class SVM specifies the functional players involved in determining the fate of HTLV-1 infection toward the development of cancer (ATLL) or neurological disorder (HAM/TSP)
title_fullStr Integration of gene co-expression analysis and multi-class SVM specifies the functional players involved in determining the fate of HTLV-1 infection toward the development of cancer (ATLL) or neurological disorder (HAM/TSP)
title_full_unstemmed Integration of gene co-expression analysis and multi-class SVM specifies the functional players involved in determining the fate of HTLV-1 infection toward the development of cancer (ATLL) or neurological disorder (HAM/TSP)
title_short Integration of gene co-expression analysis and multi-class SVM specifies the functional players involved in determining the fate of HTLV-1 infection toward the development of cancer (ATLL) or neurological disorder (HAM/TSP)
title_sort integration of gene co-expression analysis and multi-class svm specifies the functional players involved in determining the fate of htlv-1 infection toward the development of cancer (atll) or neurological disorder (ham/tsp)
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8765610/
https://www.ncbi.nlm.nih.gov/pubmed/35041720
http://dx.doi.org/10.1371/journal.pone.0262739
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