Associations between self-reported symptoms and circulating protein biomarkers: A scoping review protocol

Abstract

Background Studies linking self-reported symptoms to circulating protein biomarkers are increasing, partly driven by the rising number of protein biomarkers being identified. Despite research advances, current reviews that synthesise these studies are typically disease-specific. A broader, diagnosis-agnostic and multidisciplinary scoping review can uncover shared biological patterns associated with symptoms across different conditions and can generate insights that advance precision health and symptom science. This scoping review protocol builds on this need for a broad approach as it aims to consolidate current knowledge on self-reported symptom and circulating protein biomarker associations, identify potential patterns, and provide relevant insights for clinical practice and future research. Methods The protocol is aligned with the PRISMA and JBI guidelines for scoping reviews. The search strategy includes original peer-reviewed journal research articles examining associations between self-reported symptoms and protein biomarkers in blood plasma or serum. Searches will be conducted from PubMed, CINAHL, Embase, and Web of Science databases. A preliminary search retrieved more than 30,000 articles, prompting a pilot test of the Artificial Intelligence (AI)-assisted review screening tool ASReview. The pilot demonstrated time savings, refined methodological decisions, and confirmed the feasibility of proceeding with the review. Therefore, screening will be conducted using ASReview, with a total of five reviewers involved in the process. Data extraction will focus on single self-reported symptoms and circulating protein biomarker pairs that have a reported association. Analysis will involve counting and mapping these associations to identify potential patterns. The protocol was registered with the Open Science Framework (OSF) https://osf.io/bku3f . Discussion This protocol provides a structured and transparent approach for conducting a large-scale scoping review. By adhering to established guidelines, the protocol provides a more comprehensive, standardised, exact, and reproducible accumulation of knowledge, while acknowledging potential limitations. The expected results can contribute to summarise the current understanding of associations between self-reported symptoms and circulating protein biomarkers. This fosters the integration of symptom science and the omics field, specifically proteomics, to advance precision health.