Integration of proteomic data from cell lines and tumors

Cancer cell lines are widely used in preclinical research, yet the clinical translation of findings from cell lines remains limited. Identifying cell lines that best resemble patient tumors requires integration of molecular profiles across biologically distinct sample types. Recent advances in transcriptomic integration have demonstrated the potential of deep learning for aligning data across different sample types. However, comparable approaches for proteomic data integration remain lacking, potentially because of the prevalence of missing values in proteomic datasets. Here, we introduce ProtInt, a deep learning-based framework that integrates proteomic data from cell lines and patient tumors by combining principles from proteomic imputation and transcriptomic integration methods. We applied ProtInt to integrate label-free proteomic profiles from 771 cancer cell lines and 550 treatment-naive tumors. ProtInt outperformed batch correction and transcriptomic integration methods in aligning cell line and tumor proteomes. Comparison of the cell line proteomes before and after integration revealed recurrent increase of proteins associated with immune reaction, cell-cell communication, and interaction with the extracellular matrix, and reduction of proteins involved in transcription, post-transcriptional processing, and mitochondrial gene expression as proteomes of cell lines were adapted to resemble tumors. These results establish ProtInt as a framework for joint analysis of proteomic datasets across distinct sample types and may facilitate the identification of cell lines best suited for clinically relevant studies.