Linking cells across single-cell modalities by synergistic matching of neighborhood structure

Abstract

A wide variety of experimental methods are available to characterize different properties of single cells in a complex biosample. However, because these measurement techniques are typically destructive, researchers are often presented with complementary measurements from disjoint subsets of cells, providing a fragmented view of the cell’s biological processes. This creates a need for computational tools capable of integrating disjoint multi-omics data. Because different measurements typically do not share any features, the problem requires the integration to be done in unsupervised fashion. Recently, several methods have been proposed that project the cell measurements into a common latent space and attempt to align the corresponding low-dimensional manifolds. In this study we present an approach, Synmatch, which produces a direct matching of the cells between modalities by exploiting information about neighborhood structure in each modality. Synmatch relies on the intuition that cells which are close in one measurement space should be close in the other as well. This allows us to formulate the matching problem as a constrained supermodular optimization problem over neighborhood structures that can be solved efficiently. We show that our approach successfully matches cells in small real multi-omics datasets and performs favorably when compared to recently published state-of-the-art methods. Further, we demonstrate that Synmatch is capable of scaling to large datasets of thousands of cells. The Synmatch code and data used in this manuscript are available at https://github.com/orgs/Noble-Lab/synmatch