Journal: bioRxiv
Article Title: Single-cell lung eQTL dataset of Asian never-smokers highlights the roles of alveolar cells in lung cancer etiology
doi: 10.64898/2026.03.26.714500
Figure Lengend Snippet: TCF7L2 is a LUAD susceptibility gene involved in Wnt signaling and promoting cellular growth in the AT2 lineage a, Locus zoom plots of eQTL in AT2 cells for TCF7L2 and GWAS (Shi et al EAS, LUAD) p-values of the region (+/-100 kb) around the GWAS top SNP, rs11169089 in the 10q25.2 locus. LD (r 2 ) relationships between the variants are extracted from 1000G EAS Phase 3 v5. b, Allele frequencies difference between East Asian and European from 1000G c, Association between normalized expression of TCF7L2 and rs1196089 is shown as violin plots. 0 = reference allele, while 1 = alternative; red indicates risk allele, while blue indicates protective. Center line denotes the median, while the 25 th and 75 th percentile is marked as the lower and upper line of the box, respectively. Whiskers extend 1.5 times from the 25 th and 75 th percentiles; outliers are represented as dots. The violin width reflects the density. Note the nominal p-value threshold is 1.31e-05. d, Location of guide RNAs targeting the regions around our SNP(s) of interest. Tukey plot shows GAPDH -normalized mRNA levels of TCF7L2 in A549 cell line from 6 replicates from three independent experiments (n =18). Fold change of target gene expression over non-targeting control is shown as median with interquartile range (IQR) in a box. Whiskers extend 1.5 times IQR, with outliers shown as dots. AAVS1 represents a safe harbor site-targeting gRNA. P-values were calculated using a two-tailed Mann Whitney U test. e and f, GSEA analysis in AT2 cells comparing individuals that highly (75 th percentile) vs lowly (25 th percentile) expressed TCF7L2 . The top 5 most enriched gene sets by normalized enrichment score (NES) are shown. A positive NES indicates enrichment of the gene set compared to the reference. Cumulative enrichment score (e) and NES (f) for the top 5 gene sets are shown with a matching color for each gene set in GSEA (e) and NES (f) plots, where circle sizes are scaled to the-log 10 FDR values. g, A representative xCELLigence growth assay result among 5 independent experiments, where mean cell index with SEM of up to 4 replicates over time is shown. Beta estimates (during growth phase) from linear-mixed-effect models comparing shRNA(s) to control are shown; negative sign is indicative of decreased growth rate compared to control. *** denotes p-value < 1e-04 while ** p-value < 1e-03.
Article Snippet: TCF7L2 knockdown was confirmed by western blotting for TCF7L2 (rabbit monoclonal, Cell Signaling #2569S, 1:1000) and GAPDH (mouse monoclonal, Santa Cruz Biotechnology #47724, 1:500).
Techniques: Expressing, Targeted Gene Expression, Control, Two Tailed Test, MANN-WHITNEY, Growth Assay, shRNA