LRLoop: Feedback loops as a design principle of cell-cell communication

Genome-wide gene expression profiling, and single-cell RNA-seq in particular, allows the predictions of molecular mechanisms regulating cell-cell communication based on the expression of known ligand-receptor pairs. Currently available techniques for predicting ligand-receptor interactions are one-directional from sender to receiver cells. Here we describe LRLoop, a new method for analyzing cell-cell communication that is based on bi-directional ligand-receptor interactions, where two pairs of ligand-receptor interactions are identified that are responsive to each other, and thereby form a closed feedback loop. We assessed LRLoop using both bulk and single-cell datasets and found our method significantly reduces the false positive rate seen with existing methods. Finally, we applied LRLoop to the single-cell datasets obtained from retinal development and discovered many new bi-directional ligand-receptor interactions among individual cell types that potentially control proliferation, neurogenesis and/or cell fate specification.