Ancestry Matters in Decoding Immunity

Area of Science:

• Immunology
• Genomics
• Bioinformatics

Background:

• Existing single-cell genomics resources exhibit significant European ancestry bias.
• A comprehensive immune cell atlas is crucial for understanding human immune diversity and regulation.
• Addressing ancestry bias is vital for equitable and accurate genomic research.

Purpose of the Study:

• To establish a population-scale immune multi-omics atlas for Chinese adults.
• To mitigate ancestry bias in single-cell genomics data.
• To enable cell-type-resolved regulatory mapping and assess noncoding variant effects.

Main Methods:

• Profiling over 10 million peripheral blood mononuclear cells from 428 Chinese adults.
• Utilizing paired single-cell RNA sequencing (scRNA-seq) and single-cell Assay for Transposase-Accessible Chromatin sequencing (scATAC-seq).
• Developing CIMA-Comprehensive Long-read Mapping (CIMA-CLM) to integrate chromatin features with transcriptomic context.

Main Results:

• Creation of the Chinese Immune Multi-Omics Atlas (CIMA), a large-scale resource.
• Mitigation of European ancestry bias in immune cell genomics.
• Enabled cell type-resolved regulatory mapping across diverse immune populations.
• Demonstrated CIMA-CLM's capability in predicting chromatin accessibility and noncoding variant effects, particularly in FOXP3+ regulatory T cells.

Conclusions:

• CIMA provides a valuable, ancestry-diverse resource for immune system research.
• The atlas facilitates deeper understanding of immune cell regulation and function.
• CIMA-CLM advances the analysis of noncoding genetic variation in immune cells.