CellPHIE: Integrating Pathway Discovery With Pooled Profiling of Perturbations Uncovers Pathways of Huntington's Disease, Including Genetic Modifiers of Neuronal Development and Morphology.

ABSTRACT: Genomic screens and GWAS are powerful tools for identifying disease-modifying genes, but it is often challenging to understand the pathways by which these genes function. Here, we take an integrated approach that combines network analysis and an imaging-based pooled genetic perturbation study to examine modifiers of Huntington's disease (HD). The computational analysis highlighted several genes in a subnetwork enriched for modifiers of neuronal development and morphology. To test the functional roles of these genes, we developed an experimental pipeline that allows pooled CRISPRi KD of 21 genes in human iPSC-derived neurons followed by optical analysis of genotypes, neuronal arborization, multiplexed pathway activity and morphological fingerprint readout. This approach recovered known gene

SUBMITTER: Kang B 

PROVIDER: S-EPMC11870572 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature