Title:   Analysis and modeling of single-cell genomics data to drive biomedical discovery and innovation

Abstract 
In recent years, the emerging single-cell technologies provide unprecedented opportunities for studying many challenging biomedical problems, especially in the cell differentiation and cancer biology areas, in which there exists tremendous cell heterogeneity.  In this talk, I will discuss how to make novel biological discoveries or medical innovations in the cell differentiation studies that will benefit public health by analyzing, modeling, and visualizing large-scale single-cell genomics datasets.  First, I will present a novel computational method on reconstructing cell differentiation trajectories and the underlying regulatory networks from the time-series single-cell RNA-seq data.  Unlike other existing single-cell expression based trajectory inference methods, the proposed model can deal with the dropout noise very efficiently, and it is one of the very first methods that can infer a list of cell fate dictating regulators for the differentiation process. Besides, the model has incorporated interactive visualization functions, which can dynamically generate appropriate visualizations based on the interests of the users. With the computational model, we have discovered and experimentally verified many novel regulators for the lung and heart developmental processes. Second, I will talk about how to fully exploit the single-cell RNA-seq data to reconstruct the cell differentiation trajectories better. Most existing methods are only using the gene expression information from the single-cell RNA-seq data, and other information associated with those single-cell RNA-seq reads are neglected. Here, we have shown that such neglected information (e.g., mutations) can be very informative for trajectory inference. The cell differentiation trajectories can be significantly improved by combing the “mutations” and gene expression information from the single-cell RNA-seq data together.  Lastly, I will also talk about how to innovate the start-of-the-art protocol for differentiating iPSCs to lung epithelial cells by computationally modeling the single-cell RNA-seq data. With a careful designing of the single-cell experiment and the following computational modeling and visualization of the generated single-cell genomics dataset, we have found a significant reason for the cell fate divergence in the studied differentiation process. By repressing the identified pathway at the predicted time point by our model, we have dramatically improved the efficiency of the start-of-the-art differentiation protocol.