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Articles 1 - 4 of 4
Full-Text Articles in Medicine and Health Sciences
A Context-Forward In Vivo Functional Genomics Platform For Target Discovery And Establishing Vulnerability Context In Pancreatic Cancer, Johnathon Rose, Johnathon Lynn Rose
A Context-Forward In Vivo Functional Genomics Platform For Target Discovery And Establishing Vulnerability Context In Pancreatic Cancer, Johnathon Rose, Johnathon Lynn Rose
Dissertations & Theses (Open Access)
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a very poor patient prognosis (5-year survival of ≤ 7%). While transcriptional profiling has aided in the classification of this disease into at least two broader subtypes, this alone has so far been insufficient to inform on more nuanced patterns of oncogenic dependency. We hypothesized that a more comprehensive and granular characterization of PDAC disease diversity is required to establish relevant context for targeted therapy. To this end, we sought to establish an integrated platform to: i) more comprehensively characterize differential oncogenic signaling across our tumor models, and ii) establish …
Expediting Rare Disease Diagnosis: A Call To Bridge The Gap Between Clinical And Functional Genomics., Samantha N. Hartin, John C. Means, Joseph Alaimo, Scott T. Younger
Expediting Rare Disease Diagnosis: A Call To Bridge The Gap Between Clinical And Functional Genomics., Samantha N. Hartin, John C. Means, Joseph Alaimo, Scott T. Younger
Manuscripts, Articles, Book Chapters and Other Papers
Approximately 400 million people throughout the world suffer from a rare disease. Although advances in whole exome and whole genome sequencing have greatly facilitated rare disease diagnosis, overall diagnostic rates remain below 50%. Furthermore, in cases where accurate diagnosis is achieved the process requires an average of 4.8 years. Reducing the time required for disease diagnosis is among the most critical needs of patients impacted by a rare disease. In this perspective we describe current challenges associated with rare disease diagnosis and discuss several cutting-edge functional genomic screening technologies that have the potential to rapidly accelerate the process of distinguishing …
Inherited Causes Of Clonal Haematopoiesis In 97,691 Whole Genomes, Alexander G. Bick, Joshua S. Weinstock, Satish K. Nandakumar, Charles P. Fulco, Erik L. Bao, Seyedeh M. Zekavat, Mindy D. Szeto, Juan M. Peralta, Joanne E. Curran, John Blangero
Inherited Causes Of Clonal Haematopoiesis In 97,691 Whole Genomes, Alexander G. Bick, Joshua S. Weinstock, Satish K. Nandakumar, Charles P. Fulco, Erik L. Bao, Seyedeh M. Zekavat, Mindy D. Szeto, Juan M. Peralta, Joanne E. Curran, John Blangero
School of Medicine Publications and Presentations
Age is the dominant risk factor for most chronic human diseases, but the mechanisms through which ageing confers this risk are largely unknown1. The age-related acquisition of somatic mutations that lead to clonal expansion in regenerating haematopoietic stem cell populations has recently been associated with both haematological cancer2,3,4 and coronary heart disease5—this phenomenon is termed clonal haematopoiesis of indeterminate potential (CHIP)6. Simultaneous analyses of germline and somatic whole-genome sequences provide the opportunity to identify root causes of CHIP. Here we analyse high-coverage whole-genome sequences from 97,691 participants of diverse …
Multiplexed Crispr Libraries For Cancer Functional Genomics, Jintan Liu
Multiplexed Crispr Libraries For Cancer Functional Genomics, Jintan Liu
Dissertations & Theses (Open Access)
High-throughput forward genetic screenings are invaluable tools to systematically explore genetic interactions and to link gene disruption with disease contexts. The adaptation of CRISPR/Cas9 has improved the sensitivity and specificity of functional screenings. Despite this advance, there remains a long-standing need to improve functional screenings with smaller and more versatile pooled libraries. Capitalizing on the inherent multiplexing capability of a class 2 CRISPR enzyme AsCpf1, we developed a multiplexed, high throughput screening strategy that has avoided the usual trade-off between library size and library penetration, allowing library minimization without sacrificing gene targeting efficiency. We optimized the AsCpf1 protein for functional …