Changxi Chi

Changxi Chi, Jun Xia, Jingbo Zhou et al.

Predicting genetic perturbations enables the identification of potentially crucial genes prior to wet-lab experiments, significantly improving overall experimental efficiency. Since genes are the foundation of cellular life, building gene regulatory networks (GRN) is essential to understand and predict the effects of genetic perturbations. However, current methods fail to fully leverage gene-related information, and solely rely on simple evaluation metrics to construct coarse-grained GRN. More importantly, they ignore functional differences between biotypes, limiting the ability to capture potential gene interactions. In this work, we leverage pre-trained large language model and DNA sequence model to extract features from gene descriptions and DNA sequence data, respectively, which serve as the initialization for gene representations. Additionally, we introduce gene biotype information for the first time in genetic perturbation, simulating the distinct roles of genes with different biotypes in regulating cellular processes, while capturing implicit gene relationships through graph structure learning (GSL). We propose GRAPE, a heterogeneous graph neural network (HGNN) that leverages gene representations initialized with features from descriptions and sequences, models the distinct roles of genes with different biotypes, and dynamically refines the GRN through GSL. The results on publicly available datasets show that our method achieves state-of-the-art performance.

Jiabei Cheng, Changxi Chi, Jingbo Zhou et al.

In single-cell perturbation prediction, a central task is to forecast the effects of perturbing a gene unseen in the training data. The efficacy of such predictions depends on two factors: (1) the similarity of the target gene to those covered in the training data, which informs model (epistemic) uncertainty, and (2) the quality of the corresponding training data, which reflects data (aleatoric) uncertainty. Both factors are critical for determining the reliability of a prediction, particularly as gene perturbation is an inherently stochastic biochemical process. In this paper, we propose PRESCRIBE (PREdicting Single-Cell Response wIth Bayesian Estimation), a multivariate deep evidential regression framework designed to measure both sources of uncertainty jointly. Our analysis demonstrates that PRESCRIBE effectively estimates a confidence score for each prediction, which strongly correlates with its empirical accuracy. This capability enables the filtering of untrustworthy results, and in our experiments, it achieves steady accuracy improvements of over 3% compared to comparable baselines.

Changxi Chi, Hang Shi, Qi Zhu et al.

The rapid development of spatial transcriptomics(ST) enables the measurement of gene expression at spatial resolution, making it possible to simultaneously profile the gene expression, spatial locations of spots, and the matched histopathological images. However, the cost for collecting ST data is much higher than acquiring histopathological images, and thus several studies attempt to predict the gene expression on ST by leveraging their corresponding histopathological images. Most of the existing image-based gene prediction models treat the prediction task on each spot of ST data independently, which ignores the spatial dependency among spots. In addition, while the histology images share phenotypic characteristics with the ST data, it is still challenge to extract such common information to help align paired image and expression representations. To address the above issues, we propose a Multi-view Graph Contrastive Learning framework with HSIC-bottleneck Regularization(ST-GCHB) aiming at learning shared representation to help impute the gene expression of the queried imagingspots by considering their spatial dependency.