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Fig. 2 STARR-seq identification of SCZ-associated regulatory SNPs with biased allelic enhancer activity.A Schematic representation of the high-throughput STARR-seq workflow used to assess biased allelic activity of 351 candidate schizophrenia-associated variants. This process involves synthesizing oligonucleotides centered on each SNP, cloning them into the hSTARR-seq_ORI vector, and introducing them into four cell lines for analysis. B Volcano plots displaying the differences in regulatory activity for all SNP allele fragments across four cell lines: HEK-293T, Neuro-2a, SH-SY5Y, and PC-12. The fold change (FC) represents the expression change between the output (RNA transcripts) and input (plasmid library). SNPs showing significantly increased expression (log₂FC > 0.585, false discovery rate [FDR] < 0.05) are highlighted in red. Those with significantly decreased expression (log₂FC<−0.585, FDR < 0.05), identified as candidate silencers, are depicted in blue. All other SNP fragments, considered inactive, are shown in gray. C Heatmap illustrating biased allelic enhancer SNPs (baaSNPs) identified across the four cell lines. The full cell color represents the log₂ fold change (logFC), using a diverging color scale centered at 0 (blue for negative logFC, red for positive logFC, white for neutral), with values capped at −6 and +6. Statistical significance is indicated with asterisks (*p < 0.05, **p < 0.01, ***p < 0.001).