Dataset Open Access

Immune disease risk variants regulate gene expression dynamics during CD4+ T cell activation

Soskic, Blagoje; Cano-Gamez, Eddie; Smyth, Deborah J.; Ambridge, Kirsty; Ke, Ziying; Bossini-Castillo, Lara; Kaplanis, Joanna; Ramirez-Navarro, Lucia; Nakic, Nikolina; Esparza-Gordillo, Jorge; Rowan, Wendy; Wille, Dawid; Tough, David F.; Bronson, Paola G.; Trynka, Gosia

During activation, T cells undergo extensive changes in gene expression which shape the properties of cells to exert their effector function. Therefore, understanding the genetic regulation of gene expression during T cell activation provides essential insights into how genetic variants influence the response to infections and immune diseases. We generated a single-cell map of expression quantitative trait loci (eQTL) across a T cell activation time-course. We profiled 655,349 CD4+ naive and memory T cells, capturing transcriptional states of unstimulated cells and three time points of cell activation in 119 healthy individuals. We identified 38 cell clusters, including stable clusters such as central and effector memory T cells and transient clusters that were only present at individual time points of activation, such as interferon-responding cells. We mapped eQTLs using a T cell activation trajectory and identified 6,407 eQTL genes, of which a third (2,265 genes) were dynamically regulated during T cell activation. We integrated this information with GWAS variants for immune-mediated diseases and observed 127 colocalizations, with significant enrichment in dynamic eQTLs. Immune disease loci colocalized with genes that are involved in the regulation of T cell activation, and genes with similar functions tended to be perturbed in the same direction by disease risk alleles. Our results emphasize the importance of mapping context-specific gene expression regulation, provide insights into the mechanisms of genetic susceptibility of immune diseases, and help prioritize new therapeutic targets.

This dataset comprises of summary stats for eQTLs identified in the study (parquet files) and the ones which passed significance threshold  (tensor_out.tar.gz archive). Files are described by cell subset (CD4 Naive, CD 4 Memory, TEMRA, TCM, etc.), time since activation (16h, 4h, 5days)  as described in the publication (preprint https://doi.org/10.1101/2021.12.06.470953)

Files (5.7 GB)
Name Size
CD4_Memory_stim_16h_500kb_combined.parquet
md5:3164d9daa092b29b79be15026b944220
124.6 MB Download
CD4_Memory_stim_40h_500kb_combined.parquet
md5:427dd3596a44e0fd844d2f78d3172744
125.6 MB Download
CD4_Memory_stim_5d_500kb_combined.parquet
md5:9d748dc7031a185e93f3a9b4ef360f08
129.6 MB Download
CD4_Memory_uns_0h_500kb_combined.parquet
md5:c2c0f3ceb1029061c45fa1a528e55e5c
130.6 MB Download
CD4_Naive_stim_16h_500kb_combined.parquet
md5:739390964df1637c26aa1872b7cddb1f
123.5 MB Download
CD4_Naive_stim_40h_500kb_combined.parquet
md5:89c8ba1871b893b09bcad84aa2486b37
121.4 MB Download
CD4_Naive_stim_5d_500kb_combined.parquet
md5:15e2eb981835aad0f7f0d46bd65899c7
126.8 MB Download
CD4_Naive_uns_0h_500kb_combined.parquet
md5:0cb76c91c75031162fa2f845ff57dd08
127.8 MB Download
HSP_16h_500kb_combined.parquet
md5:2d57b92a687dc4e4cc8e2642d2dbfc08
115.9 MB Download
nTreg_0h_500kb_combined.parquet
md5:6f2c410defa3a567163759665101960f
122.3 MB Download
nTreg_16h_500kb_combined.parquet
md5:7ca5a74f09564f86cf0194711e6e5271
122.0 MB Download
nTreg_40h_500kb_combined.parquet
md5:e3d2c55c511fc9c04774e20a37dbf883
122.6 MB Download
T_ER-stress_5d_500kb_combined.parquet
md5:6bf00a931e008c480cc99bb9bb18673c
133.2 MB Download
TCM_0h_500kb_combined.parquet
md5:57467c686b3c55858cf2c21f8094b65a
129.8 MB Download
TCM_16h_500kb_combined.parquet
md5:76006856b9088afd832dda1dd9520781
120.9 MB Download
TCM_40h_500kb_combined.parquet
md5:0e245e60272794dfc203f3c9fd35e7e0
122.5 MB Download
TCM_5d_500kb_combined.parquet
md5:03eb5a08c3720c05e2d69194e2d17afd
130.3 MB Download
TCM_LA_500kb_combined.parquet
md5:db417813bf60b68452de6e5bb628653d
126.8 MB Download
TEM_0h_500kb_combined.parquet
md5:969c4db84c4aea71fc6b17846c92a692
129.3 MB Download
TEM_16h_500kb_combined.parquet
md5:136829402dd5102fc5ee7560aa8c6f67
122.5 MB Download
TEM_40h_500kb_combined.parquet
md5:e0adb528f93f41caa651e888b69d923f
122.9 MB Download
TEM_5d_500kb_combined.parquet
md5:3ea5761f37db412e65bf0516ec8b52bd
127.5 MB Download
TEM_HLApositive_40h_500kb_combined.parquet
md5:a2bd5bcfef43c5482d0bd8b028d21c16
123.6 MB Download
TEM_HLApositive_5d_500kb_combined.parquet
md5:e352851201b52c370fd89a3334389403
128.9 MB Download
TEM_LA_500kb_combined.parquet
md5:3dee806a7df6429358c655baf1610743
127.5 MB Download
TEMRA_0h_500kb_combined.parquet
md5:d1450af88407e2bb27218f6f07eb87ce
123.2 MB Download
TEMRA_16h_500kb_combined.parquet
md5:508db3e451702d6e67ada824b787dc0f
120.7 MB Download
TEMRA_40h_500kb_combined.parquet
md5:f4f9ad542eacb49457c5e9fb3e7c7563
122.3 MB Download
TEMRA_5d_500kb_combined.parquet
md5:c1a6f9f7ce8a3108e805677fc1cfea60
127.1 MB Download
TEMRA_LA_500kb_combined.parquet
md5:0b0cfbdeac1d4207e049b42a67c011bf
106.8 MB Download
tensor_out.tar.gz
md5:2c925acf930816951acf3e7851eee6d0
38.3 MB Download
TM_cycling_5d_500kb_combined.parquet
md5:aad36aeeab79addde79a9fb7882bf89f
120.4 MB Download
TM_ER-stress_40h_500kb_combined.parquet
md5:b298532317852803798b6a27afd01a10
125.0 MB Download
TN2_40h_500kb_combined.parquet
md5:9a084b52a316503974965fcdad673e6e
116.7 MB Download
TN_0h_500kb_combined.parquet
md5:c5157972bd773b9fc0e2e0f8ec0cc775
127.8 MB Download
TN_16h_500kb_combined.parquet
md5:b15bd8de7d80ff081a8fd4a6246fb7b2
119.9 MB Download
TN_40h_500kb_combined.parquet
md5:0e9aa2ae3858c16d7489675e0dbd516f
120.3 MB Download
TN_5d_500kb_combined.parquet
md5:a4143b3cb44463aa4989817f9b0510ed
127.4 MB Download
TN_cycling_40h_500kb_combined.parquet
md5:8e2bc31d19c55afc7c27f99ed927624c
120.3 MB Download
TN_cycling_5d_500kb_combined.parquet
md5:b5304840d4040efba9299d1b2263ced9
124.8 MB Download
TN_HSP_5d_500kb_combined.parquet
md5:a0a2be44185209df115f5ae474908d63
128.2 MB Download
TN_IFN_16h_500kb_combined.parquet
md5:a1f6dc4e64614bc12be7084c0c9c6fd3
112.9 MB Download
TN_IFN_40h_500kb_combined.parquet
md5:00fd135417e4610189f48b3c6ea4f88c
120.4 MB Download
TN_IFN_5d_500kb_combined.parquet
md5:9d9bf389c8d3217de87902f563d2cb55
126.7 MB Download
TN_IFN_LA_500kb_combined.parquet
md5:2ab7581983e134cefb3786ed269756ca
119.9 MB Download
TN_LA_500kb_combined.parquet
md5:7aeb439924ec9ab4ed73cc5280e92d40
124.2 MB Download
TN_NFKB_500kb_combined.parquet
md5:3ae5131f6460f907e09485fe54b791e0
117.1 MB Download
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