Uncovering Dark Mass in Population Proteomics: Pan-analysis of Single Amino Acid Polymorphism Relevant to Cognition and Aging

Overview

Journal Cell Genom

Date 2025 Jan 31

PMID 39889701

Authors

Xiaojing Gao

Yuanyuan Yin

Yiqian Chen

Ling Lu

Jian Zhao

Xu Lin

Jiarui Wu

Qingrun Li

Rong Zeng

Affiliations

Soon will be listed here.

Abstract

Human proteome data across populations have been analyzed extensively to reveal protein quantitative associations with physiological or pathological states, while the single amino acid polymorphism (SAP) has been rarely investigated. In this work, we introduce a pan-SAP workflow that relies on pan-database searching independent of individual genome sequencing. Using ten cohorts comprising 2,004 individuals related to cognition disorder and aging, we quantify the SAP sites in key proteins, such as apolipoprotein E (APOE) in plasma and cerebrospinal fluid at the proteome level. Specifically, the quantification of heterozygous APOE-C112R, including its abundance and ratio, provides insights into the dosage effect and relationship with cognition disorder, which cannot be interpreted at the genomic level. Furthermore, our approach could precisely track age-related changes in APOE-C112R levels. Taken together, this pan-SAP workflow uncovered existing but hidden SAPs in multi-populations, connecting SAP quantification to disease progression and paving the way for broader proteomic investigations in complex diseases.

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