Abstract 1927: Transcell: In silico characterization of genomic landscape and cellular responses from gene expressions through a two-step transfer learning

Abstract

Abstract Gene expression profiling of new or modified cell lines becomes routine today; however, obtaining comprehensive molecular characterization and cellular responses for a variety of cell lines, including those derived from underrepresented groups, is not trivial when resources are minimal. Using gene expression to predict other measurements has been actively explored; however, systematic investigation of its predictive power in various measurements has not been well studied. We present TransCell, a two-step deep transfer learning framework that utilizes the knowledge derived from pan-cancer tumor samples to predict molecular features and responses. Compared to the five state-of-art methods, TransCell has the best performance in predicting metabolite, gene effect score (or genetic dependency), and drug sensitivity, and has comparable performance in predicting mutation, copy number variation, and protein expression. Notably, TransCell improved the performance by over 50% in drug sensitivity prediction and achieved a correlation of 0.7 in gene effect score prediction. Furthermore, predicted drug sensitivities revealed potential repurposing candidates for new 100 pediatric cancer cell lines, and predicted gene effect scores reflected BRAF resistance in melanoma cell lines. Together, TransCell demonstrates its remarkable predictive power that enables in silico molecular characterization of understudied cell lines. Citation Format: Shan-Ju Yeh, Ruoqiao Chen, Jing Xing, Mengying Sun, Ke Liu, Shreya Paithankar, Jiayu Zhou, Bin Chen. Transcell: In silico characterization of genomic landscape and cellular responses from gene expressions through a two-step transfer learning [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1927.