Chinese Immune Multi-Omics Atlas

Area of Science:

• Immunology
• Genomics
• Systems Biology

Background:

• Human peripheral blood shows significant molecular and cellular heterogeneity.
• The mechanisms driving this immune cell diversity are not fully understood.

Purpose of the Study:

• To create a comprehensive multi-omics atlas of Chinese adult peripheral blood immune cells.
• To characterize molecular variations associated with sex, age, and genetic factors.
• To build a reference for immune-related disease research.

Main Methods:

• Multi-omics analysis of over 10 million circulating immune cells from 428 Chinese adults.
• Construction of an enhancer-driven gene regulatory network.
• Identification of enhancer genes (eGenes) and chromatin accessibility peaks (caPeaks) at single-cell resolution.
• Application of a cell language model (CIMA-CLM) for predicting chromatin accessibility and variant effects.

Main Results:

• Established a robust gene regulatory network with 237 regulons.
• Identified 9600 eGenes and 52,361 caPeaks across different immune cell types.
• Revealed pleiotropic associations between immune disease risk loci, expression quantitative trait loci (eQTLs), and chromatin accessibility QTLs (caQTLs).
• Demonstrated CIMA-CLM's capability in predicting chromatin accessibility and evaluating noncoding variant impacts.

Conclusions:

• The Chinese Immune Multi-Omics Atlas (CIMA) provides unprecedented cell-type-resolved molecular characterization of human immune cells.
• CIMA offers a valuable resource for dissecting the genetic and regulatory underpinnings of immune variation and disease.
• The findings highlight the interplay between genetic variants, chromatin accessibility, and gene expression in shaping immune cell phenotypes.