Groundbreaking Functional Network Analysis in Hepatobiliary Disorders: Identifying Novel Therapeutic Targets through Whole-Exome Sequencing

<b>Background: </b>Hepatolithiasis (HL) is a common condition in hepatobiliary surgery, frequently complicated by hepatatrophia. This study aimed to identify mutated genes in HL combined with hepatatrophia specimens and construct their mutation landscape using whole-exome sequencing (WES).<b>Methods: </b>The differences in somatic mutations and copy number variants (CNV) between HL and normal control (NC) specimens were examined utilizing WES data. Subsequently, Hub genes within HL specimens were identified using the GeneCards database. Following this, The mutation frequency and interaction modes of these hub genes were explored, and their potential molecular mechanisms were investigated. Additionally, a competing endogenous RNA (ceRNA) network and a transcription factors (TFs)-mRNA network were constructed to elucidate the regulatory mechanisms governing the hub genes. Therapeutic drugs targeting these hub genes were predicted using the DrugBank database, and molecular docking was utilized to assess the binding energies. Finally, the expression of hub genes was validated via reverse-transcription quantitative PCR (RT-qPCR).