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Full-Text Articles in Life Sciences
Biases And Blind-Spots In Genome-Wide Crispr-Cas9 Knockout Screens, Merve Dede
Biases And Blind-Spots In Genome-Wide Crispr-Cas9 Knockout Screens, Merve Dede
Dissertations & Theses (Open Access)
Adaptation of the bacterial CRISPR-Cas9 system to mammalian cells revolutionized the field of functional genomics, enabling genome-scale genetic perturbations to study essential genes, whose loss of function results in a severe fitness defect. There are two types of essential genes in a cell. Core essential genes are absolutely required for growth and proliferation in every cell type. On the other hand, context-dependent essential genes become essential in an environmental or genetic context. The concept of context-dependent gene essentiality is particularly important in cancer, since killing cancer cells selectively without harming surrounding healthy tissue remains a major challenge. The toxicity of …
Computational Approaches To Delineate Transcriptional And Functional Heterogeneity In Pancreatic Cancer, Sanjana Srinivasan
Computational Approaches To Delineate Transcriptional And Functional Heterogeneity In Pancreatic Cancer, Sanjana Srinivasan
Dissertations & Theses (Open Access)
Pancreatic ductal adenocarcinoma (PDAC) is an incurable disease characterized by poor survival, dense desmoplastic stroma and activating mutations in KRAS (>90%). These tumors are highly complex ecosystems composed of molecularly distinct sub-populations that exhibit a spectrum of genetic features and associated phenotypes. Despite recent advances in the transcriptomic characterization of PDAC into at least two tumor subtypes, this alone has been insufficient to define more specific patterns of oncogenic dependency. To fully leverage advancements in next generation sequencing and functional genomics, we have sought to establish computational methodologies to aid in refined target discovery, and to develop a novel …