hReg-CNCC

The hReg-CNCC software tool is a comprehensive computational framework designed to analyze and understand Cranial Neural Crest Cells (CNCC) regulatory mechanisms. CNCCs, critical for craniofacial development, originate from the cephalic region, including the forebrain, midbrain, and hindbrain, and migrate to the craniofacial region, where they differentiate into various cell types. The process involves a complex regulatory network, the disruption of which can lead to craniofacial abnormalities and birth defects.

hReg-CNCC integrates paired gene expression and chromatin accessibility data to reconstruct a genome-wide human Regulatory network specific to CNCC. It employs consensus optimization to predict high-quality regulatory relationships. It elucidates the architecture of transcription factors (TFs) at different stages of CNCC development, such as neural plate border formation, specification, and migration.

A notable feature of hReg-CNCC is its capability to annotate genetic variants associated with human facial morphology and craniofacial disease traits, including identifying the regulatory roles of transcription factors and their target genes and linking distal and combinatorial regulations of SNPs to core TFs like ALX1, thereby establishing associations with facial distances and rare cranial diseases.

Furthermore, hReg-CNCC provides insights into the evolutionary aspects of craniofacial development by connecting DNA sequence variations, such as ultra-conserved elements and human accelerated regions, with gene expression changes and phenotypic outcomes.