The high cis/trans ratios indicated the high library quality of our HIOEC DLO Hi-C data.33 We performed A/B compartment analysis and topologically associated domain (TAD) analysis using HIOEC DLO Hi-C data (Fig. 3b, TADs shown in Supplementary Table 5), and found that IRF6, a gene widely considered to be pathogenic for cleft palate, was located in the active compartment (compartment A), indicating that IRF6 is in a transcriptionally active genomic region, and more importantly, it is close to a TAD boundary, where mutations might reconstruct the 3D structure of chromatin (Fig. 3c). This evidence concerns the gene IRF6 and cleft palate.