MIGGRI: A multi-instance graph neural network model for inferring gene regulatory networks for Drosophila from spatial expression images.

Recent breakthrough in spatial transcriptomics has brought great opportunities for exploring gene regulatory networks (GRNs) from a brand-new perspective. Especially, the local expression patterns and spatio-temporal regulation mechanisms captured by spatial expression images allow more delicate delineation of the interplay between transcript factors and their target genes. However, the complexity and size of spatial image collections pose significant challenges to GRN inference using image-based methods. Extracting regulatory information from expression images is difficult due to the lack of supervision and the multi-instance nature of the problem, where a gene often corresponds to multiple images captured from different views. While graph models, particularly graph neural networks, have emerged as a promising method for leveraging underlying structure information from known GRNs, incorporating expression images into graphs is not straightforward. To address these challenges, we propose a two-stage approach, MIGGRI, for capturing comprehensive regulatory patterns from image collections for each gene and known interactions. Our approach involves a multi-instance graph neural network (GNN) model for GRN inference, which first extracts gene regulatory features from spatial expression images via contrastive learning, and then feeds them to a multi-instance GNN for semi-supervised learning. We apply our approach to a large set of Drosophila embryonic spatial gene expression images. MIGGRI achieves outstanding performance in the inference of GRNs for early eye development and mesoderm development of Drosophila, and shows robustness in the scenarios of missing image information. Additionally, we perform interpretable analysis on image reconstruction and functional subgraphs that may reveal potential pathways or coordinate regulations. By leveraging the power of graph neural networks and the information contained in spatial expression images, our approach has the potential to advance our understanding of gene regulation in complex biological systems.