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Development Of Graphical Models And Statistical Physics Motivated Approaches To Genomic Investigations, Yashwanth Lagisetty

Dissertations & Theses (Open Access)

Identifying genes involved in disease pathology has been a goal of genomic research since the early days of the field. However, as technology improves and the body of research grows, we are faced with more questions than answers. Among these is the pressing matter of our incomplete understanding of the genetic underpinnings of complex diseases. Many hypotheses offer explanations as to why direct and independent analyses of variants, as done in genome-wide association studies (GWAS), may not fully elucidate disease genetics. These range from pointing out flaws in statistical testing to invoking the complex dynamics of epigenetic processes. In the …

Computational Approaches To Understand Chemoresistance & Tumor Evolution Using Longitudinal Clinical Data And Lineage Tracing, Sahil Seth

Dissertations & Theses (Open Access)

Tumors are highly heterogeneous and dynamic, continually adapting and evolving in response to their microenvironment as well as external perturbations. Multi-region (spatial) and single cell sequencing has enabled us to anatomize the heterogeneity further and provide evidence of its association with chemo and drug resistance. To investigate this further we took two different approaches to understand the chemo-resistance, and functional heterogeneity in Triple negative breast cancer (TNBC) and Pancreatic ductal carcinoma in situ (PDAC) from an evolutionary perspective.

The first approach was to leverage tumor profiling from an ongoing randomized clinical trial in triple-negative breast cancer (ARTEMIS) to assess mechanisms …