Graph neural networks for spatial gene expression analysis of the developing human heart

Single-cell RNA sequencing and in situ sequencing were combined in a recent study of the developing human heart to explore the transcriptional landscape at three developmental stages. However, the method used in the study to create the spatial cellular maps has some limitations. It relies on image s...

Full description

Bibliographic Details
Main Author: Yuan, Xiao
Format: Others
Language:English
Published: Uppsala universitet, Institutionen för biologisk grundutbildning 2020
Subjects:
Online Access:http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-427330
Description
Summary:Single-cell RNA sequencing and in situ sequencing were combined in a recent study of the developing human heart to explore the transcriptional landscape at three developmental stages. However, the method used in the study to create the spatial cellular maps has some limitations. It relies on image segmentation of the nuclei and cell types defined in advance by single-cell sequencing. In this study, we applied a new unsupervised approach based on graph neural networks on the in situ sequencing data of the human heart to find spatial gene expression patterns and detect novel cell and sub-cell types. In this thesis, we first introduce some relevant background knowledge about the sequencing techniques that generate our data, machine learning in single-cell analysis, and deep learning on graphs. We have explored several graph neural network models and algorithms to learn embeddings for spatial gene expression. Dimensionality reduction and cluster analysis were performed on the embeddings for visualization and identification of biologically functional domains. Based on the cluster gene expression profiles, locations of the clusters in the heart sections, and comparison with cell types defined in the previous study, the results of our experiments demonstrate that graph neural networks can learn meaningful representations of spatial gene expression in the human heart. We hope further validations of our clustering results could give new insights into cell development and differentiation processes of the human heart.