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Deep Learning Gene Regulatory Network Dynamics from Transcriptomes

Abstract

Regulation of gene expression is critical for all life processes. RNAseq allows for the investigation of the expression state and the inference of gene regulatory net- works (GRNs). The GRN reveals mechanisms of disease and development both at an organismal and cellular level. Constructing GRNs from expression data is done by de- tecting statistical relationships over a series of samples. However, these relationships are noisy and do not take into account many important variables. To explore one such limitation, I implemented dual RNAseq to investigate the regulatory mechanisms that occur between both host and virus transcriptomes in SARS-CoV-2 infected samples (Chapter 1). To address the temporal aspect of GRNs, I developed a statistical frame- work for detecting relationships between transcription factors and their targets from inferred trajectory progressions (”pseudotime”) in single-cells (Chapter 2). Finally, I developed an interpretable, time-aware deep learning transformer for modeling disease progression and demonstrate its ability to identify gene programs that promote breast cancer resistance post-treatment (Chapter 3).

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