Multi-omics study of ABCA1 in sepsis: Integrating mendelian randomisation, single-cell transcriptomics, in silico
1Xingtai People's Hospital, Hebei Medical University, Xingtai, Hebei Province, China.
Computational Biology and Chemistry
|August 8, 2026
Summary
ATP-binding cassette transporter A1 (ABCA1) shows a protective trend against sepsis and is primarily expressed in monocytes. Potential drug candidates, including Dihydroergotamine, were identified for sepsis treatment.
Area of Science:
- Immunology
- Genetics
- Pharmacology
Background:
- Sepsis involves a dynamic immune response, shifting from inflammation to immunosuppression.
- The role of ATP-binding cassette transporter A1 (ABCA1) in sepsis, its cellular origin, and therapeutic potential are not well understood.
Purpose of the Study:
- To investigate the genetic and cellular basis of ABCA1's role in sepsis.
- To identify potential therapeutic targets for sepsis by exploring ABCA1's drug-binding capabilities.
Main Methods:
- Mendelian randomization (MR) analysis using ABCA1 expression quantitative trait loci (eQTLs) and sepsis genome-wide association studies (GWAS).
- Single-cell transcriptomics to determine ABCA1 expression patterns in immune cells.
- In silico knockout of ABCA1 in monocytes and subsequent pathway analysis.
- Two-stage virtual drug screening of FDA-approved drugs against ABCA1.
Main Results:
- MR analysis indicated a potential protective effect of ABCA1 against sepsis.
- ABCA1 is predominantly expressed in CD16+ monocytes.
- In silico ABCA1 knockout affected lipid transport and fever-related pathways.
- Virtual screening identified Dihydroergotamine and Nilotinib as potential ABCA1 binders.
Conclusions:
- ABCA1 is specifically expressed in CD16+ monocytes and influences lipid-related pathways.
- Dihydroergotamine emerged as a leading drug candidate for sepsis therapy targeting ABCA1.
- This study provides multi-level evidence supporting ABCA1 as a protective factor and therapeutic target in sepsis.