Sparsely-Connected Autoencoder (SCA) for single cell RNAseq data mining

Single-cell RNA sequencing (scRNAseq) is an essential tool to investigate cellular heterogeneity. Thus, it would be of great interest being able to disclose biological information belonging to cell subpopulations, which can be defined by clustering analysis of scRNAseq data. In this manuscript, we show the efficacy of sparsely-connected autoencoder (SCA) as tool for the functional mining of single cells clusters. We show that SCA can be used as tool to uncover hidden features associated to scRNAseq data. Our approach is strengthened by two metrics, QCC (Quality Control of Cluster) and QCM (Quality Control of Model), which respectively allow to evaluate the ability of SCA to reconstruct a cells cluster and to evaluate the overall quality of the neural network model. Our data indicate that SCA encoded space, derived by different experimentally validated data (TF targets, miRNA targets, Kinase targets, and cancer-related immune signatures), can be used to grasp single cell cluster-specific functional features. In our implementation, SCA efficacy comes from its ability to reconstruct only specific clusters, thus indicating only those clusters where the SCA encoding space is a key element for cells aggregation. SCA analysis is implemented as module in rCASC framework and it is supported by a GUI to simplify it usage for biologists and medical personnel.