Detecting Fear-Memory-Related Genes from Neuronal ScRNA-seq Data by Diverse Distributions and Bhattacharyya Distance

The detection of differentially expressed genes (DEGs) is one of most important computational challenges in the analysis of single-cell RNA sequencing (scRNA-seq) data. However, due to the high heterogeneity and dropout noise inherent in scRNAseq data, challenges in detecting DEGs exist when using a single distribution of gene expression levels, leaving much room to improve the precision and robustness of current DEG detection methods. Here, we propose the use of a new method, DEGman, which utilizes several possible diverse distributions in combination with Bhattacharyya distance. DEGman can automatically select the best-fitting distributions of gene expression levels, and then detect DEGs by permutation testing of Bhattacharyya distances of the selected distributions from two cell groups. Compared with several popular DEG analysis tools on both large-scale simulation data and real scRNA-seq data, DEGman shows an overall improvement in the balance of sensitivity and precision. We applied DEGman to scRNA-seq data of mouse neurons to detect fear-memory-related genes that are significantly differentially expressed in neurons with and without fear memory. DEGman detected well-known fear-memory-related genes and many novel candidates. Interestingly, we found 25 DEGs in common in five neuron clusters that are functionally enriched for synaptic vesicles, indicating that the coupled dynamics of synaptic vesicles across in neurons plays a critical role in remote memory formation. The proposed method leverages the advantage of the use of diverse distributions in DEG analysis, exhibiting better performance in analyzing composite scRNA-seq datasets in real applications.