Fatigue-Related Gene Associations in CD14 Cells of HIV/AIDS Patients and Controls

2.50
Hdl Handle:
http://hdl.handle.net/10755/157667
Type:
Presentation
Title:
Fatigue-Related Gene Associations in CD14 Cells of HIV/AIDS Patients and Controls
Abstract:
Fatigue-Related Gene Associations in CD14 Cells of HIV/AIDS Patients and Controls
Conference Sponsor:Western Institute of Nursing
Conference Year:2009
Author:Voss, Joachim G., RN, PhD
P.I. Institution Name:University of Washington School of Nursing, Biobehavioral Nursing and Health Systems
Title:Assistant Professor
Contact Address:Box 357266, Seattle, WA, 98195, USA
Contact Telephone:206-616-7819
Co-Authors:Joe Adelsberger, Associate Scientist; Marinos C. Dalakas, MD, Professor and Chief of the Neuromuscular Division; Robert L. Danner, Senior Investigator; Adrian Dobra, PhD; Joseph Kovacs, MD, Senior Investigator; Carolea Logun, Staff Scientist; Caryn Morse,
Purpose and Aims: Our purpose was to study gene associations in monocytes of ART-treated fatigued and non-fatigued HIV patients compared to healthy controls using an oligonucleotide mitochondria-specific gene expression microarray that contained 4712 probe-sets.  Our aim was to discover how HIV status and subjective fatigue severity relate to gene expression pathways of mitochondria-related genes. Background: Fatigue is a debilitating symptom that affects a high proportion of HIV/AIDS patients throughout their illness trajectory. Defining features of fatigue include consistent or episodic tiredness and exhaustion for more than six months, which are not resolved by sleep and rest. Progressive fatigue leads to declines in physical, emotional and social functioning and contributes to job loss and lack of adherence to antiretroviral therapy (ART). Mitochondrial dysfunction caused by HIV itself or ART may be related to the extent of fatigue experienced by HIV patients. Methods: We collected CD 14+ cells via Dynabead Monocyte Negative Isolation kit from existing apheresis samples of 5 healthy, 6 fatigued and 6 non-fatigued HIV patients. Cells were sorted and bead purified to 98% purity and RNA was extracted using standard methods. To reduce variability of initial RNA yield, RNA was one-round amplified and reverse transcribed with a biotin-enhanced single-round amplification kit.  Data were analyzed using dependency networks for genome-wide data. The raw expression data were background corrected and normalized using GC Robust Multi-array Average. After the removal of 112 control probes included on the Affymetrix custom chip, the resulting dataset comprised 4712 probes with 12 cases and 5 controls. Results: In comparing the 12 cases (HIV+) and 5 controls (HIV-) we identified 33 genes with posterior inclusion probabilities greater than 0.01. We then sought to identify a dependency network involving these 33 genes and HIV status. The logistic regressions identified for HIV status in the dependency network classified all 17 samples correctly. In a similar analysis comparing the 6 patients with low fatigues scores (0-3) to those with high fatigue scores (4-10) we identified 33 different genes with posterior inclusion probabilities greater than 0.01. We again sought to identify a dependency network involving these 33 genes and fatigue status. The logistic regressions identified for fatigue status in the dependency network classified all 12 samples correctly. These prediction results hold when we do leave-one-out cross-validation. We have identified 27 genes related to fatigue (two of which are associated with the function of the inner mitochondrial membrane) and 33 genes related to HIV status (three of which are associated with the Krebs cycle function). We confirmed these results with real-time polymerase chain reaction experiments for six genes. Implications: Novel liquid association techniques assisted us in potentially identifying relevant associations between mitochondrial genes and subjective ratings of fatigue in HIV patients which will need to be verified in an independent data set. Understanding the basic biological mechanisms of fatigue might allow us to design new behavioral and pharmacological interventions and possibly monitor the effectiveness of these novel treatments.
Repository Posting Date:
26-Oct-2011
Date of Publication:
17-Oct-2011
Sponsors:
Western Institute of Nursing

Full metadata record

DC FieldValue Language
dc.typePresentationen_GB
dc.titleFatigue-Related Gene Associations in CD14 Cells of HIV/AIDS Patients and Controlsen_GB
dc.identifier.urihttp://hdl.handle.net/10755/157667-
dc.description.abstract<table><tr><td colspan="2" class="item-title">Fatigue-Related Gene Associations in CD14 Cells of HIV/AIDS Patients and Controls</td></tr><tr class="item-sponsor"><td class="label">Conference Sponsor:</td><td class="value">Western Institute of Nursing</td></tr><tr class="item-year"><td class="label">Conference Year:</td><td class="value">2009</td></tr><tr class="item-author"><td class="label">Author:</td><td class="value">Voss, Joachim G., RN, PhD</td></tr><tr class="item-institute"><td class="label">P.I. Institution Name:</td><td class="value">University of Washington School of Nursing, Biobehavioral Nursing and Health Systems</td></tr><tr class="item-author-title"><td class="label">Title:</td><td class="value">Assistant Professor</td></tr><tr class="item-address"><td class="label">Contact Address:</td><td class="value">Box 357266, Seattle, WA, 98195, USA</td></tr><tr class="item-phone"><td class="label">Contact Telephone:</td><td class="value">206-616-7819</td></tr><tr class="item-email"><td class="label">Email:</td><td class="value">vossj@u.washington.edu</td></tr><tr class="item-co-authors"><td class="label">Co-Authors:</td><td class="value">Joe Adelsberger, Associate Scientist; Marinos C. Dalakas, MD, Professor and Chief of the Neuromuscular Division; Robert L. Danner, Senior Investigator; Adrian Dobra, PhD; Joseph Kovacs, MD, Senior Investigator; Carolea Logun, Staff Scientist; Caryn Morse,</td></tr><tr><td colspan="2" class="item-abstract">Purpose and Aims: Our purpose was to study gene associations in monocytes of ART-treated fatigued and non-fatigued HIV patients compared to healthy controls using an oligonucleotide mitochondria-specific gene expression microarray that contained 4712 probe-sets.&nbsp; Our aim was to discover how HIV status and subjective fatigue severity relate to gene expression pathways of mitochondria-related genes. Background: Fatigue is a debilitating symptom that affects a high proportion of HIV/AIDS patients throughout their illness trajectory. Defining features of fatigue include consistent or episodic tiredness and exhaustion for more than six months, which are not resolved by sleep and rest. Progressive fatigue leads to declines in physical, emotional and social functioning and contributes to job loss and lack of adherence to antiretroviral therapy (ART). Mitochondrial dysfunction caused by HIV itself or ART may be related to the extent of fatigue experienced by HIV patients. Methods: We collected CD 14+ cells via Dynabead Monocyte Negative Isolation kit from existing apheresis samples of 5 healthy, 6 fatigued and 6 non-fatigued HIV patients. Cells were sorted and bead purified to 98% purity and RNA was extracted using standard methods. To reduce variability of initial RNA yield, RNA was one-round amplified and reverse transcribed with a biotin-enhanced single-round amplification kit.&nbsp; Data were analyzed using dependency networks for genome-wide data. The raw expression data were background corrected and normalized using GC Robust Multi-array Average. After the removal of 112 control probes included on the Affymetrix custom chip, the resulting dataset comprised 4712 probes with 12 cases and 5 controls. Results: In comparing the 12 cases (HIV+) and 5 controls (HIV-) we identified 33 genes with posterior inclusion probabilities greater than 0.01. We then sought to identify a dependency network involving these 33 genes and HIV status. The logistic regressions identified for HIV status in the dependency network classified all 17 samples correctly. In a similar analysis comparing the 6 patients with low fatigues scores (0-3) to those with high fatigue scores (4-10) we identified 33 different genes with posterior inclusion probabilities greater than 0.01. We again sought to identify a dependency network involving these 33 genes and fatigue status. The logistic regressions identified for fatigue status in the dependency network classified all 12 samples correctly. These prediction results hold when we do leave-one-out cross-validation. We have identified 27 genes related to fatigue (two of which are associated with the function of the inner mitochondrial membrane) and 33 genes related to HIV status (three of which are associated with the Krebs cycle function). We confirmed these results with real-time polymerase chain reaction experiments for six genes. Implications: Novel liquid association techniques assisted us in potentially identifying relevant associations between mitochondrial genes and subjective ratings of fatigue in HIV patients which will need to be verified in an independent data set. Understanding the basic biological mechanisms of fatigue might allow us to design new behavioral and pharmacological interventions and possibly monitor the effectiveness of these novel treatments.</td></tr></table>en_GB
dc.date.available2011-10-26T20:05:22Z-
dc.date.issued2011-10-17en_GB
dc.date.accessioned2011-10-26T20:05:22Z-
dc.description.sponsorshipWestern Institute of Nursingen_GB
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