Zhiyue Zhang will present her General Exam "Best practices of multiome data analysis and application to anti-tumor immunology in obesity" on Monday, May 19, 2025 at 2:30 PM in Icahn 200.

Committee Members: Yuri Pritykin (advisor), Lydia Lynch (advisor), Mona Singh, Olga Troyanskaya

Abstract:

Technological advances in single-cell sequencing have expanded the detection of cell phenotype beyond the transcriptome, allowing for more refined characterization of cell types and discovery of novel therapeutic targets. Notably, paired scRNA-seq and scATAC-seq, called multiome data, facilitates inference of how variation in chromatin accessibility regulates gene expression and cell identity. However, unlike scRNA analysis, procedures of scATAC analysis lack consensus, mainly due to the high sparsity and the unfixed feature set of the original data. In this talk, we first present evaluating differential representations of scATAC by integrating with scRNA and validating against the pairing information of multiome data. We show that several decisions in current scATAC processing tools result in loss of information and recommend best practices of featurization and downstream analysis. Next, we demonstrate the power of multiome through an analysis of new multiome data from tumor-infiltrating CD8+ T cells in obesity. We find an enrichment of progenitor exhausted CD8+ T cells in obese tumors, and generate a new hypothesis for "the obesity paradox", namely why certain obese patients have improved response to immune checkpoint inhibitors despite displaying impaired anti-tumor immunity.

Reading List:

https://docs.google.com/document/d/1Pl6x0mOhhlj8NIXbllube2f11S-JnxglPgM0kOT-D4U/edit?usp=sharing

Everyone is invited to attend the talk, and those faculty wishing to remain for the oral exam following are welcome to do so.