Supporting data for: Mapping genetic effects on cell type-specific chromatin accessibility and annotating complex immune trait variants using single nucleus ATAC-seq in peripheral blood

Summary

In this study we performed single nucleus ATAC-seq (snATAC-seq) and genotyping in peripheral blood mononuclear cells from 13 individuals. Clustering chromatin accessibility profiles of 96,002 total nuclei identified 17 immune cell types and sub-types. We mapped chromatin accessibility QTLs (caQTLs) in each immune cell type and sub-type using individuals of European ancestry which identified 6,901 total caQTLs at FDR <10%. For 3,941 caQTLs we further annotated putative target genes of variant activity using single cell co-accessibility. We fine-mapped loci associated with 16 complex immune traits and identified immune cell caQTLs at 622 candidate causal variants.

Raw sequence data are available in NCBI GEO accession GSE199253 and GSE163160.

Description of processed data deposited here:

0_snATAC_cluster_lables_and_qc.txt : Final list of barcodes, annotated with UMAP coordinates, sample and cell type labels and QC metrics.

1_peaks_coordinates.zip : Output of MACS2 peak calling for individual cell subtypes (NARROW.PEAKS)

• act_cd4_t_peaks.narrowPeak
• adaptive_NK_peaks.narrowPeak
• cDC_peaks.narrowPeak
• cMono_peaks.narrowPeak
• cyto_cd8_t_peaks.narrowPeak
• cyto_nk_peaks.narrowPeak
• iMono_peaks.narrowPeak
• mem_b_peaks.narrowPeak
• mem_cd8_t_peaks.narrowPeak
• mkc_peaks.narrowPeak
• naive_b_peaks.narrowPeak
• naive_cd4_t_peaks.narrowPeak
• naive_cd8_t_peaks.narrowPeak
• ncMono_peaks.narrowPeak
• pDC_peaks.narrowPeak
• plasma_peaks.narrowPeak
• tReg_peaks.narrowPeak

2_co-accessibility.zip : Co-accessibility results (Cicero) of snATAC in four major blood cell types (BEDPE)

• t.filtered_coaccessible_sites4s.txt
• nk.filtered_coaccessible_sites4s.txt
• mono.filtered_coaccessible_sites4s.txt
• b.filtered_coaccessible_sites4s.txt
• annotated.coaccessible.matrix4s

3_genome_browser_tracks.zip: Genome browser tracks of PBMC cell types and subtypes (BIGWIG)

• pbmc1_15.tReg.scale_1e6.bw
• pbmc1_15.plasma.scale_1e6.bw
• pbmc1_15.naive_cd4_t.scale_1e6.bw
• pbmc1_15.naive_cd8_t.scale_1e6.bw
• pbmc1_15.ncMono.scale_1e6.bw
• pbmc1_15.mem_cd8_t.scale_1e6.bw
• pbmc1_15.naive_b.scale_1e6.bw
• pbmc1_15.mem_b.scale_1e6.bw
• pbmc1_15.cyto_nk.scale_1e6.bw
• pbmc1_15.iMono.scale_1e6.bw
• pbmc1_15.cyto_cd8_t.scale_1e6.bw
• pbmc1_15.cMono.scale_1e6.bw
• pbmc1_15.cDC.scale_1e6.bw
• pbmc1_15.adaptive_NK.scale_1e6.bw
• pbmc1_15.act_cd4_t.scale_1e6.bw

4_summary_stats.zip: Summary statistics of caQTLs in PBMC cell types, subtypes, and “bulk” like data (TSV)

## Lead only combined

• EUR_caqtl_leads_run3.tsv

## Bulk-like

• bulk_caqtl_sumstats_run3.tsv

## Cell types

• b_caqtl_sumstats_run3.tsv   
• t_caqtl_sumstats_run3.tsv
• nk_caqtl_sumstats_run3.tsv
• mono_caqtl_sumstats_run3.tsv

## Cell subtypes

• tReg_caqtl_sumstats_run3.tsv
• naive_cd4_t_caqtl_sumstats_run3.tsv
• naive_cd8_t_caqtl_sumstats_run3.tsv
• ncMono_caqtl_sumstats_run3.tsv
• naive_b_caqtl_sumstats_run3.tsv
• mem_cd8_t_caqtl_sumstats_run3.tsv
• mkc_caqtl_sumstats_run3.tsv
• mem_b_caqtl_sumstats_run3.tsv
• iMono_caqtl_sumstats_run3.tsv
• cyto_nk_caqtl_sumstats_run3.tsv
• cyto_cd8_t_caqtl_sumstats_run3.tsv
• cMono_caqtl_sumstats_run3.tsv
• cDC_caqtl_sumstats_run3.tsv
• cd8_t_caqtl_sumstats_run3.tsv
• cd4_t_caqtl_sumstats_run3.tsv
• adaptive_NK_caqtl_sumstats_run3.tsv
• act_cd4_t_caqtl_sumstats_run3.tsv

5_credible_sets.zip: Fine-mapping credible sets for loci associated with 16 complex immune traits (BED)

• Ulcerative_colitis.99credset.PPA.bed
• Type_1_diabetes.99credset.PPA.bed
• Systemic_lupus_erythematosus.99credset.PPA.bed
• Rheumatoid_arthritis.99credset.PPA.bed
• Selective_IgA_deficiency.99credset.PPA.bed
• Primary_sclerosing_cholangitis.99credset.PPA.bed
• Monocyte_count.99credset.PPA.bed
• Neutrophil_count.99credset.PPA.bed
• Lymphocyte_count.99credset.PPA.bed
• Gout.99credset.PPA.bed
• Eosinophil_count.99credset.PPA.bed
• Crohns_disease.99credset.PPA.bed
• Basophil_count.99credset.PPA.bed
• Autoimmune_vitiligo.99credset.PPA.bed
• Atopic_dermatitis.99credset.PPA.bed
• Asthma_child_onset.99credset.PPA.bed