Forward genetics combined with unsupervised classifications identified zebrafish mutants affecting biliary system formation

• DOI: 10.1016/j.ydbio.2024.05.005
• Publication Date: 2024-05-08T15:16:55Z
• Authors: Divya Jyoti Singh; Kathryn M. Tuscano; Amrhen L. Ortega; Manali Dimri; Kevin Tae; William Lee; Muslim A. Muslim; Isabela M. Rivera...; Jay L. Liu; Lain X. Pierce; Allyson McClendon; Isabel Gibson; Jodi Livesay; Takuya F. Sakaguchi
• Keywords: 0303 health sciences; 03 medical and health sciences

Impaired formation of the biliary network can lead to congenital cholestatic liver diseases; however, genes responsible for proper system and maintenance have not been fully identified. Combining computational structure analysis algorithms with a zebrafish forward genetic screen, we identified 24 new mutants that display impaired intrahepatic formation. Complementation tests suggested these mutations affect different genes. We applied unsupervised clustering unbiasedly classify recovered into three classes. Further revealed each in classes has unique phenotype on node-subtype composition distribution within network. In addition, found most are viable. those mutant fish, which already good animal models study chronic diseases, phenotypes persist adulthood. Altogether, this provides toolsets advance our understanding molecular pathways leading malformation diseases.