Large-Scale and Pan-Cancer Multi-omic Analyses with Machine Learning

Abstract

Multi-omic data analysis has been foundational in many fields of molecular biology, including cancer research. Investigation of the relationship between different omic data types reveals patterns that cannot otherwise be found in a single data type alone. With recent technological advancements in mass spectrometry (MS), MS-based proteomics has enabled the quantification of thousands of proteins in hundreds of cell lines and human tissue samples. This thesis presents several machine learning-based methods that facilitate the integrative analysis of multi-omic data. First, we reviewed five existing multi-omic data integration methods and performed a benchmarking analysis, using a large-scale multi-omic cancer cell line dataset. We evaluated the performance of these machine learning methods for drug response prediction and cancer type classification. Our result provides recommendations to researchers regarding optimal machine learning method selection for their applications. Second, we generated a pan-cancer proteomic map of 949 cancer cell lines across 40 cancer types and developed a machine learning method DeeProM to analyse the multi-omic information of these lines. This pan-cancer proteomic map (ProCan-DepMapSanger) is now publicly available and represents a major resource for the scientific community, for biomarker discovery and for the study of fundamental aspects of protein regulation. Third, we focused on publicly available multi-omic datasets of both cancer cell lines and human tissue samples and developed a Transformer-based deep learning method, DeePathNet, which integrates human knowledge with machine intelligence. We applied DeePathNet on three evaluation tasks, namely drug response prediction, cancer type classification and breast cancer subtype classification. Taken together, our analyses and methods allowed more accurate cancer diagnosis and prognosis

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