Upregulation of Apoptosis Pathway Genes in Peripheral Blood Mononuclear Cells of HIV-Infected Individuals with Antiretroviral Therapy-Associated Mitochondrial Toxicity

Foli, Yram; Ghebremichael, Musie; Li, Min; Paintsil, Elijah

doi:10.1128/aac.00522-17

Cited by 4 publications

(10 citation statements)

References 41 publications

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“…We previously also developed a classi er model to classify study participants into groups based on these two selected genes. The classi er model correctly classi ed 75% of the participants into their respective groups (21). However, using machine learning classi er algorithms (elastic net and KNN) we achieved 90% prediction accuracy using top two mRMR genes---DFFA and TNFRSF1A.…”

Section: Discussionmentioning

confidence: 91%

“…We previously analyzed the data and identified 26 out of the 84 genes differentially expressed between the cases and controls (21). We identified the 26 differentially expressed genes based on the false discovery rate (FDR) adjusted p-value using empirical Bayes moderated tests.…”

Section: Discussionmentioning

confidence: 99%

“…This study is a secondary analysis of data obtained from a previous case control study comprising of HIV infected individuals with mitochondrial toxicity (cases, n=16) and HIV uninfected individuals (controls, n=16). The rationale, organization, and recruitment of the subjects, biological procedures used have been described previously by Foli et al (21). In brief, 32 individuals were enrolled from April 2011 to March 2013 at the Yale-New Haven Hospital.. Cases were matched for age, race, and gender to HIVnegative controls.…”

Section: Study Design and Participantsmentioning

confidence: 99%

“…with mitochondrial toxicity vs HIV uninfected controls) a total of 26 of 84 genes of the apoptosis pathway were differentially expressed (21).…”

mentioning

confidence: 99%

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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

Bose

Paintsil

Ghebremichael

2021

Preprint

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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 (ART) 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 m-fold cross validation using machine learning classifiers and tested the prediction accuracy of the two mRMR genes. We next used network analysis to estimate the association between the differentially expressed genes using partial correlations, relative importance estimates, and centrality measures of each item. The Spinglass algorithm 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 90%, which clearly show that the mRMR gene sets outperforms the performance of the gene sets based on gene expression analyses. FASLG had highest centrality in cases with ABL1 in controls.Conclusion: The mRMR algorithm and network analysis revealed a new correlation of genes associated with mitochondrial toxicity.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Study Design and Participantsmentioning

confidence: 99%

“…with mitochondrial toxicity vs HIV uninfected controls) a total of 26 of 84 genes of the apoptosis pathway were differentially expressed (21).…”

mentioning

confidence: 99%

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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

Bose

Paintsil

Ghebremichael

2021

Preprint

Self Cite

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“…Some of these comorbidities could be explained by the high rates of co-infection among LTC-HIV patients, notably with Hepatitis C ( 18 , 19 ). Moreover, HAART toxicity itself increases the risk of cardiovascular disease and metabolic dysfunction via mitochondrial dysfunction, but this does not fully explain the increase in neurocognitive disorders ( 20 – 23 ). Another potential factor is the increased systemic inflammation reported in LTC- HIV infection ( 24 – 27 ).…”

Section: Introductionmentioning

confidence: 99%

Altered Immunity and Microbial Dysbiosis in Aged Individuals With Long-Term Controlled HIV Infection

et al. 2019

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The introduction of highly active antiretroviral therapy (HAART) resulted in a significant increase in life expectancy for HIV patients. Indeed, in 2015, 45% of the HIV+ individuals in the United States were ≥55 years of age. Despite improvements in diagnosis and treatment of HIV infection, geriatric HIV+ patients suffer from higher incidence of comorbidities compared to age-matched HIV- individuals. Both chronic inflammation and dysbiosis of the gut microbiome are believed to be major contributors to this phenomenon, however carefully controlled studies investigating the impact of long-term (>10 years) controlled HIV (LTC-HIV) infection are lacking. To address this question, we profiled circulating immune cells, immune mediators, and the gut microbiome from elderly (≥55 years old) LTC-HIV+ and HIV- gay men living in the Palm Springs area. LTC-HIV+ individuals had lower frequency of circulating monocytes and CD4+ T-cells, and increased frequency CD8+ T-cells. Moreover, levels of systemic INFγ and several growth factors were increased while levels of IL-2 and several chemokines were reduced. Upon stimulation, immune cells from LTC-HIV+ individuals produced higher levels of pro-inflammatory cytokines. Last but not least, the gut microbiome of LTC-HIV+ individuals was enriched in bacterial taxa typically found in the oral cavity suggestive of loss of compartmentalization, while levels of beneficial butyrate producing taxa were reduced. Additionally, prevalence of Prevotella negatively correlated with CD4+ T-cells numbers in LTC-HIV+ individuals. These results indicate that despite long-term adherence and undetectable viral loads, LTC-HIV infection results in significant shifts in immune cell frequencies and gut microbial communities.

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Brief Report: Polymorphisms in TNF-α/TNFR1 Pathway Genes Are Associated With CD4+ T-Cell Recovery in HIV-1–Infected Individuals on Antiretroviral Therapy

Silva

Alves

Silva³

et al. 2021

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Upregulation of Apoptosis Pathway Genes in Peripheral Blood Mononuclear Cells of HIV-Infected Individuals with Antiretroviral Therapy-Associated Mitochondrial Toxicity

Cited by 4 publications

References 41 publications

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

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

Altered Immunity and Microbial Dysbiosis in Aged Individuals With Long-Term Controlled HIV Infection

Brief Report: Polymorphisms in TNF-α/TNFR1 Pathway Genes Are Associated With CD4+ T-Cell Recovery in HIV-1–Infected Individuals on Antiretroviral Therapy

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