Computational Modeling of Spatiotemporal Dynamics in Single-Cell Omics Data
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Pan, Xinhai
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Abstract
Understanding how single cells divide and differentiate into different cell types in developed organs is one of the major tasks of developmental biology. Single-cell sequencing technologies have recently brought more insights into cells’ spatiotemporal dynamics. For example, Spatial Transcriptomics technologies can sequence cells’ transcriptomes and spatial locations in tissue simultaneously. On the other hand, lineage tracing technologies have enabled the reconstruction of division histories of single cells. Numerous computational algorithms have been developed to infer cells’ spatiotemporal dynamics. Different methods tend to focus on different tasks, including trajectory inference, lineage inference, spatial mapping, etc. Computationally modeling real biological events, such as cell division and differentiation processes, is key to improving the performance and interpretability of such methods.
In this dissertation, I present a suite of methods I developed throughout my PhD to reconstruct cell histories and spatial organization by leveraging gene expression, lineage tracing, and spatial information of cells. First, I introduce TedSim, my initial project, which is a simulation framework that jointly models cell divisions and cell differentiation. I then introduce LinRace, a framework for reconstructing cell lineage relationships from temporal sequencing data. Next, I present TemSOMap, a method for mapping single cells onto spatial transcriptomics data to infer their original tissue context. Finally, I introduce LineageMap, a unified computational framework that integrates lineage tracing, transcriptomics, and spatial locations to reconstruct spatially resolved lineage trees. By connecting cell lineages with spatial context and molecular states, these methods provide a more accurate and interpretable view of how complex tissues form and change over time, and provide insights into biological processes such as asymmetric cell division and migration.
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Date
2026-05
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Dissertation (PhD)