Boolean implication analysis of single-cell data predicts retinal cell type markers

Abstract

Abstract Background The retina is a complex tissue containing multiple cell types that are essential for vision. Understanding the gene expression patterns of various retinal cell types has potential applications in regenerative medicine. Retinal organoids (optic vesicles) derived from pluripotent stem cells have begun to yield insights into the transcriptomics of developing retinal cell types in humans through single cell RNA-sequencing studies. Previous methods of gene reporting have relied upon techniques in vivo using microarray data, or correlational and dimension reduction methods for analyzing single cell RNA-sequencing data computationally. We aimed to develop a state-of-the-art Boolean method that filtered out noise, could be applied to a wide variety of datasets and lent insight into gene expression over differentiation. Results Here, we present a bioinformatic approach using Boolean implication to discover genes which are retinal cell type-specific or involved in retinal cell fate. We apply this approach to previously published retina and retinal organoid datasets and improve upon previously published correlational methods. Our method improves the prediction accuracy of marker genes of retinal cell types and discovers several new high confidence cone and rod-specific genes. Conclusions The results of this study demonstrate the benefits of a Boolean approach that considers asymmetric relationships. We have shown a statistically significant improvement from correlational, symmetric methods in the prediction accuracy of retinal cell-type specific genes. Furthermore, our method contains no cell or tissue-specific tuning and hence could impact other areas of gene expression analyses in cancer and other human diseases.