Biophysical Modeling for Gene Expression and Evolution

Author: Felce, Catherine E.

Year: 2026

Degree: Dissertation (Ph.D.)

Advisor: Pachter, Lior S.

Committee Members: Phillips, Robert B.; Thomson, Matthew; Pennell, Matthew; Pachter, Lior S.

Option: Physics

DOI: 10.7907/chmp-kt37

Abstract

Principled biophysical modeling is a necessary foundation for analyzing RNA sequencing data. In recent years, higher quality data for other data modalities at single-cell resolution have become available. I present joint biophysical models combining two of these modalities, chromatin accessibility measurements (ATAC-seq) and protein counts, individually with single-cell transcriptomic data, and give preliminary data results. I consider the extension of biophysically motivated models to the field of phylogenetics. I present competing mechanistic hypotheses for gene expression evolution and test them via parametrized single-cell cross-species data. I also consider a physics-inspired model for population-level evolution via maternal effects and interacting subpopulations.

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