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

BMC Medical Genomics

Elijah Paintsil¹  Musie Ghebremichael²  Eliezer Bose³ 

[1] Department of Pediatrics, Yale University School of Medicine, New Haven, CT, USA;Harvard Medical School, Cambridge, MA, USA;Ragon Institute of MGH, MIT and Harvard, 400 Technology Square, 02129, Cambridge, MA, USA;Massachusetts General Hospital Institute of Health Professions, Boston, MA, USA;

关键词: HIV;    Apoptosis;    Antiretroviral therapy;    Mitochondrial toxicity;    Machine learning;    Minimum redundancy maximum relevance (mRMR);   

DOI  :  10.1186/s12920-021-01136-1

来源: Springer

【 摘 要 】

BackgroundWe 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.MethodsThis 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.ResultsThe 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.ConclusionThe mRMR algorithm and network analysis revealed a new correlation of genes associated with mitochondrial toxicity.

【 授权许可】

CC BY