Multiplexing Proteomic and Ingenuity Pathway Analysis of Attention/Working Memory in Virally Suppressed Women with HIV: A Feasibility Study
<b>Background/Objectives:</b> Individual plasma protein biomarkers have been shown to correlate with cognitive performance in people with HIV (PWH). This study aimed to investigate the association between plasma proteomic signatures and attention/working memory in virologically well-controlled women with HIV (WWH). <b>Methods:</b> Seventy-seven WWH from three Women's Interagency HIV Study (WIHS) sites completed neuropsychological (NP) testing and a blood draw. Selected protein biomarkers (200 total) were analyzed using a multiplexing method. <b>Results:</b> Random forest analysis was used to identify the top 10 biomarkers that were each positively or negatively associated with attention/working memory. Ingenuity pathway analysis (IPA) was used to facilitate data interpretation. Tumor necrosis factor receptor 1 (TNF RI), TNF RII, interleukin 1 receptor 1 (IL-1RI), and IL-6R were negatively associated with attention/working memory. <b>Conclusions:</b> Based on the IPA, two gene signaling networks were proposed for associating these plasma protein biomarkers with attention/working memory function. This novel methodology demonstrates how gene networks can be identified using blood draws in conjunction with cognitive assessment, and then used in random forest analysis, to derive value that can be put in IPA.
Authors
- Igho Ofotokun
- David E. Vance (ORCID: https://orcid.org/0000-0002-0498-6263)
- Raha Maryam Dastgheyb (ORCID: https://orcid.org/0000-0002-4992-711X)
- Leah H. Rubin (ORCID: https://orcid.org/0000-0003-2749-6328)
- Mirjam-Colette Kempf (ORCID: https://orcid.org/0000-0003-3796-4906)
- Yanxun Xu (ORCID: https://orcid.org/0000-0001-5554-8637)
- Deborah J. Konkle‐Parker (ORCID: https://orcid.org/0000-0002-3319-8442)
- Daniel Y. Li
- Yuezhe Wang
- Travis Ptacek (ORCID: https://orcid.org/0000-0002-4949-0149)
- Anandi N. Sheth (ORCID: https://orcid.org/0000-0002-6305-2727)
- Jodie A. Dionne
- Wei Li (ORCID: https://orcid.org/0000-0002-7530-4872)
- Ge Wang (ORCID: https://orcid.org/0000-0003-0571-5745)
Institutions
- Johns Hopkins University (US)
- Emory University (US)
- Johns Hopkins Medicine (US)
- University of Mississippi Medical Center (US)
- University of Alabama at Birmingham (US)
- Tongji Hospital (CN)
- Huazhong University of Science and Technology (CN)
- SUNY College of Optometry (US)
Publication Details
- Journal
- Diagnostics
- Published
- 2025-10-21
- DOI
- https://doi.org/10.3390/diagnostics15202649
- Primary Topic
- HIV Research and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Northwestern University
- Georgia Clinical and Translational Science Alliance
- National Institutes of Health
- University of California, San Francisco
- Center for AIDS Research, University of Alabama at Birmingham
- National Institute on Alcohol Abuse and Alcoholism
- National Institute on Aging
- National Heart, Lung, and Blood Institute
- National Institute of Mental Health
- National Institute on Drug Abuse
- National Cancer Institute
- National Institute on Deafness and Other Communication Disorders
- National Institute of Nursing Research
- National Institute of Allergy and Infectious Diseases
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Institute of Neurological Disorders and Stroke
- National Institute of Dental and Craniofacial Research
- National Institute on Minority Health and Health Disparities
- Center for AIDS Research, University of North Carolina at Chapel Hill
- Clinical and Translational Science Institute, University of California, Los Angeles