Multiplexing Proteomic and Ingenuity Pathway Analysis of Attention/Working Memory in Virally Suppressed Women with HIV: A Feasibility Study

TL;DR

This study explores how blood proteins relate to attention and memory in HIV-positive women, using a new method to identify key biomarkers and gene networks.

Contribution

The study introduces a novel methodology combining proteomics, random forest analysis, and gene network interpretation for cognitive function in HIV.

Findings

TNF RI, TNF RII, IL-1RI, and IL-6R were negatively associated with attention/working memory.

Two gene signaling networks were identified linking plasma proteins to cognitive function.

The method successfully integrated blood-based biomarkers with cognitive assessments.

Abstract

Background/Objectives: 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). Methods: 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. Results: 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. Conclusions: 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.

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