Minimum redundancy maximal relevance gene selection of apoptosis pathway genes in peripheral blood mononuclear cells of HIV-infected patients with antiretroviral therapy-associated mitochondrial toxicity

Abstract Background We previously identified differentially expressed genes on the basis of false discovery rate adjusted P value using empirical Bayes moderated tests. However, that approach yielded a subset of differentially expressed genes without accounting for redundancy between the selected ge...

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Autores principales:	Eliezer Bose, Elijah Paintsil, Musie Ghebremichael
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	HIV Apoptosis Antiretroviral therapy Mitochondrial toxicity Machine learning Minimum redundancy maximum relevance (mRMR) Internal medicine RC31-1245 Genetics QH426-470
Acceso en línea:	https://doaj.org/article/4852f6ed494946979659d8eb4b7a3711
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spelling	oai:doaj.org-article:4852f6ed494946979659d8eb4b7a37112021-12-05T12:05:27ZMinimum redundancy maximal relevance gene selection of apoptosis pathway genes in peripheral blood mononuclear cells of HIV-infected patients with antiretroviral therapy-associated mitochondrial toxicity10.1186/s12920-021-01136-11755-8794https://doaj.org/article/4852f6ed494946979659d8eb4b7a37112021-12-01T00:00:00Zhttps://doi.org/10.1186/s12920-021-01136-1https://doaj.org/toc/1755-8794Abstract Background We previously identified differentially expressed genes on the basis of false discovery rate adjusted P value using empirical Bayes moderated tests. However, that approach yielded a subset of differentially expressed genes without accounting for redundancy between the selected genes. Methods This study is a secondary analysis of a case–control study of the effect of antiretroviral therapy on apoptosis pathway genes comprising of 16 cases (HIV infected with mitochondrial toxicity) and 16 controls (uninfected). We applied the maximum relevance minimum redundancy (mRMR) algorithm on the genes that were differentially expressed between the cases and controls. The mRMR algorithm iteratively selects features (genes) that are maximally relevant for class prediction and minimally redundant. We implemented several machine learning classifiers and tested the prediction accuracy of the two mRMR genes. We next used network analysis to estimate and visualize the association among the differentially expressed genes. We employed Markov Random Field or undirected network models to identify gene networks related to mitochondrial toxicity. The Spinglass model was used to identify clusters of gene communities. Results The mRMR algorithm ranked DFFA and TNFRSF1A, two of the upregulated proapoptotic genes, on the top. The overall prediction accuracy was 86%, the two mRMR genes correctly classified 86% of the participants into their respective groups. The estimated network models showed different patterns of gene networks. In the network of the cases, FASLG was the most central gene. However, instead of FASLG, ABL1 and LTBR had the highest centrality in controls. Conclusion The mRMR algorithm and network analysis revealed a new correlation of genes associated with mitochondrial toxicity.Eliezer BoseElijah PaintsilMusie GhebremichaelBMCarticleHIVApoptosisAntiretroviral therapyMitochondrial toxicityMachine learningMinimum redundancy maximum relevance (mRMR)Internal medicineRC31-1245GeneticsQH426-470ENBMC Medical Genomics, Vol 14, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	HIV Apoptosis Antiretroviral therapy Mitochondrial toxicity Machine learning Minimum redundancy maximum relevance (mRMR) Internal medicine RC31-1245 Genetics QH426-470
spellingShingle	HIV Apoptosis Antiretroviral therapy Mitochondrial toxicity Machine learning Minimum redundancy maximum relevance (mRMR) Internal medicine RC31-1245 Genetics QH426-470 Eliezer Bose Elijah Paintsil Musie Ghebremichael Minimum redundancy maximal relevance gene selection of apoptosis pathway genes in peripheral blood mononuclear cells of HIV-infected patients with antiretroviral therapy-associated mitochondrial toxicity
description	Abstract Background We previously identified differentially expressed genes on the basis of false discovery rate adjusted P value using empirical Bayes moderated tests. However, that approach yielded a subset of differentially expressed genes without accounting for redundancy between the selected genes. Methods This study is a secondary analysis of a case–control study of the effect of antiretroviral therapy on apoptosis pathway genes comprising of 16 cases (HIV infected with mitochondrial toxicity) and 16 controls (uninfected). We applied the maximum relevance minimum redundancy (mRMR) algorithm on the genes that were differentially expressed between the cases and controls. The mRMR algorithm iteratively selects features (genes) that are maximally relevant for class prediction and minimally redundant. We implemented several machine learning classifiers and tested the prediction accuracy of the two mRMR genes. We next used network analysis to estimate and visualize the association among the differentially expressed genes. We employed Markov Random Field or undirected network models to identify gene networks related to mitochondrial toxicity. The Spinglass model was used to identify clusters of gene communities. Results The mRMR algorithm ranked DFFA and TNFRSF1A, two of the upregulated proapoptotic genes, on the top. The overall prediction accuracy was 86%, the two mRMR genes correctly classified 86% of the participants into their respective groups. The estimated network models showed different patterns of gene networks. In the network of the cases, FASLG was the most central gene. However, instead of FASLG, ABL1 and LTBR had the highest centrality in controls. Conclusion The mRMR algorithm and network analysis revealed a new correlation of genes associated with mitochondrial toxicity.
format	article
author	Eliezer Bose Elijah Paintsil Musie Ghebremichael
author_facet	Eliezer Bose Elijah Paintsil Musie Ghebremichael
author_sort	Eliezer Bose
title	Minimum redundancy maximal relevance gene selection of apoptosis pathway genes in peripheral blood mononuclear cells of HIV-infected patients with antiretroviral therapy-associated mitochondrial toxicity
title_short	Minimum redundancy maximal relevance gene selection of apoptosis pathway genes in peripheral blood mononuclear cells of HIV-infected patients with antiretroviral therapy-associated mitochondrial toxicity
title_full	Minimum redundancy maximal relevance gene selection of apoptosis pathway genes in peripheral blood mononuclear cells of HIV-infected patients with antiretroviral therapy-associated mitochondrial toxicity
title_fullStr	Minimum redundancy maximal relevance gene selection of apoptosis pathway genes in peripheral blood mononuclear cells of HIV-infected patients with antiretroviral therapy-associated mitochondrial toxicity
title_full_unstemmed	Minimum redundancy maximal relevance gene selection of apoptosis pathway genes in peripheral blood mononuclear cells of HIV-infected patients with antiretroviral therapy-associated mitochondrial toxicity
title_sort	minimum redundancy maximal relevance gene selection of apoptosis pathway genes in peripheral blood mononuclear cells of hiv-infected patients with antiretroviral therapy-associated mitochondrial toxicity
publisher	BMC
publishDate	2021
url	https://doaj.org/article/4852f6ed494946979659d8eb4b7a3711
work_keys_str_mv	AT eliezerbose minimumredundancymaximalrelevancegeneselectionofapoptosispathwaygenesinperipheralbloodmononuclearcellsofhivinfectedpatientswithantiretroviraltherapyassociatedmitochondrialtoxicity AT elijahpaintsil minimumredundancymaximalrelevancegeneselectionofapoptosispathwaygenesinperipheralbloodmononuclearcellsofhivinfectedpatientswithantiretroviraltherapyassociatedmitochondrialtoxicity AT musieghebremichael minimumredundancymaximalrelevancegeneselectionofapoptosispathwaygenesinperipheralbloodmononuclearcellsofhivinfectedpatientswithantiretroviraltherapyassociatedmitochondrialtoxicity
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Minimum redundancy maximal relevance gene selection of apoptosis pathway genes in peripheral blood mononuclear cells of HIV-infected patients with antiretroviral therapy-associated mitochondrial toxicity

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