Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 16 of 16 for “"Gene essentiality"”.
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Using machine learning to understand the link between gene essentiality, gene expression and the chemosensitivity of cancer cells
… encompassing various drug IC50 values, ensured generalization of the models across different drugs and cell
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Inferring context-specific essentiality networks using large-scale CRISPR-KO screens
… DepMap and Project Score, revealed that a lot of genes are essential, i.e. required, in only a subset of cell lines. These context-essential genes offer insights into vulnerabilities of different cancer types and provide promising targets for personalized cancer therapies. However, the challenge …
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Modelling fitness and stability of G protein-coupled receptor variants
… in a wide variety of diseases2. Protein-altering genetic variants have complex effects on the biophysical and functional properties of GPCRs. Understanding the biophysical and functional effects of protein-altering variants in GPCRs using computational variant effect prediction methods could help …
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Whole genome doubling confers unique genetic vulnerabilities on tumor cells
Whole genome doubling (WGD) generates genetically unstable tetraploid cells that fuel tumorigenesis. Cells that undergo WGD must acquire adaptive characteristics to accommodate their tetraploid state, and these adaptations may confer unique vulnerabilities that can be exploited therapeutically. We …
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Defining cell state regulators in cancers using single-cell analysis and CRISPR-Cas9 screening
… accessible, our understanding of cancer heterogeneity and its impact on clinical outcomes are being realised. Whilst genomic variation has been extremely useful for cancer stratification and development of targeted therapies, they do not always underpin variable therapeutic responses, …
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Molecular mechanisms controlling complex traits in yeast
… libraries to examine how mutations in the same gene but in two different genetic backgrounds of S. cerevisiae, S288c and [summation]1278b, can lead different phenotypes for two traits: gene essentiality and agar adhesion. We found that the genomes of the S288c and [summation]1278b strains are …
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Development and application of a general method for somatic cell genetics
Genetic analysis, or genetic screening, is an efficient method for identifying the set of genes involved in a biological process. In microorganisms, powerful techniques enable systematic loss-of-function screens, which have yielded critical insights into the molecular basis of many fundamental …
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Biases and Blind-Spots In Genome-Wide Crispr-Cas9 Knockout Screens
… 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 …
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SYNTHETIC DOSAGE LETHAL INTERACTIONS OF POLO-LIKE KINASE 1 AND THEIR APPLICATION IN CANCER THERAPEUTICS
… personalizing cancer treatment, but tumour heterogeneity presents a challenge in the identification of effective targets. Polo-like kinase 1 is overexpressed near ubiquitously across cancer types and dysregulation of polo-like kinase 1 is closely tied to chromosomal instability and tumour …
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Genome-Scale Quantification of Target Vulnerability in Mycobacterium Tuberculosis
<p>Essential bacterial genes orchestrate core biological processes and represent the targets of nearly all antibacterial drugs. Traditional genetic approaches such as knockout studies and transposon mutagenesis have cataloged hundreds of essential bacterial genes but provide no basis on which to …
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Probabilistic Reconstruction and Comparative Systems Biology of Microbial Metabolism
… study the long-term the evolution of growth and gene-essentiality phenotypes. The results show that, over billions of years of evolution, the conservation of bacterial phenotypic properties drops by a similar fraction per unit time following an exponential decay. The analysis provides a framework …
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Expanding cancer therapy options through genome-scale identification of synthetic lethal paralogs
… lethality is a form of context-dependent gene essentiality in which dual inactivation of a gene pair leads to cell death but single-gene inactivation does not affect viability. When one synthetic lethal gene is inactivated in cancer, targeting the remaining gene results in tumor cell death …
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Predicting Genetic Interactions Using Functional Interaction Networks
<p>Mapping genetic interactions is central to understanding cellular systems and identifying therapeutic vulnerabilities, particularly in the context of cancer. Among these interactions, synthetic lethality, where simultaneous loss of two genes is lethal but loss of either alone is tolerated, …
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Systems biology of lung diseases: a multi-perspective view from host and pathogen
… As a case study, I gathered publicly available gene expression data from 1,470 microarray samples of 6 lung phenotypes from 26 independent experimental studies and 769 RNA-seq samples of 2 lung phenotypes from 4 independent studies. I found that the RCV-ISV performance discrepancy is greater in …
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Investigating the Molecular Mechanisms Underlying Ku Essentiality in Human Cells
… human cell viability but is dispensable in mice. Essentiality in human cells was previously suggested to be due to Ku’s role in maintaining human telomere length. To study the underlying cause of Ku’s essentiality in humans, a conditional Ku70 knockout TREx-293 cell line was created using …
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Identifying the Genetic Factors in Natural Genome Backgrounds That May Modulate Phenotypic Outcomes in C. elegans
Loss-of-function mutations in essential genes can lead to a severe phenotype characterized by reproductive stress or hindrance in development and survival. Whilst in some individuals these lethal mutations cause severe phenotypes, in others, phenotypic variability is observed. One of the factors …