Supporting data for Stratifying gene vulnerabilities among patient-derived gastric cancer organoids by CRISPR-Cas9 screens

Raw data files and analysed data for thesis titled "Stratifying gene vulnerabilities among patient-derived gastric cancer organoids by CRISPR-Cas9 screens".Related computational scripts for graph plotting and sequencing alignments.

Gastric cancer is the fifth most common malignant tumour worldwide, with an estimated 5-year survival rate of less than 20%. Gastric cancer is classified into multiple subtypes based on the Lauren Classification. The main subtypes based on histomorphology are the intestinal and diffuse subtypes, while there is also a mixed subtype. Gastric cancer carrying ARHGAP fusion is shown to have a worse prognosis when compared to ARHGAP fusion-negative ones, and ARHGAP fusion mutation is highly associated with the diffuse subtype. There are different fusion mutations present in gastric cancer, and among the fusion mutations, CLDN18-ARHGAP26 and CTNND1-ARHGAP26 are the fusion mutations with high prevalence in the population. This research aims to identify the genetic factors contributing to gastric cancer development, with a particular focus on identifying potential therapeutic targets for ones with ARHGAP fusion mutations. Building upon our previous genome-wide CRISPR-Cas9 screening data in an ARHGAP fusion-containing organoid line, we selected top-performing genes to construct sub-pool libraries for screening in a panel of organoid lines derived from patients with different gastric cancer subtypes. Through high-throughput CRISPR screening, computational analyses (MAGeCK, BAGEL, JACKs and Trinity CTAT), and downstream validation (Growth competition assays), this work identifies common and distinct vulnerabilities among gastric cancer subtypes.