Connectome: computation and visualization of cell-cell signaling topologies in single-cell systems data

Single-cell RNA-sequencing data can revolutionize our understanding of the patterns of cell-cell and ligand-receptor connectivity that influence the function of tissues and organs. However, the quantification and visualization of these patterns are major computational and epistemological challenges. Here, we present Connectome , a software package for R which facilitates rapid calculation, and interactive exploration, of cell-cell signaling network topologies contained in single-cell RNA-sequencing data. Connectome can be used with any reference set of known ligand-receptor mechanisms. It has built-in functionality to facilitate differential and comparative connectomics, in which complete mechanistic networks are quantitatively compared between systems. Connectome includes computational and graphical tools designed to analyze and explore cell-cell connectivity patterns across disparate single-cell datasets. We present approaches to quantify these topologies and discuss some of the biologic theory leading to their design. ### Competing Interest Statement LEN is a founder and shareholder in Humacyte, Inc, which is a regenerative medicine company. Humacyte produces engineered blood vessels from allogeneic smooth muscle cells for vascular surgery. LEN's spouse has equity in Humacyte, and LEN serves on the Humacyte Board of Directors. LEN is an inventor on patents that are licensed to Humacyte and that produce royalties for LEN. LEN has received an unrestricted research gift to support research in her laboratory at Yale. Humacyte did not influence the conduct, description or interpretation of the findings in this report. NK reports personal fees from Boehringer Ingelheim, Third Rock, Pliant, Samumed, NuMedii, Indalo, Theravance, LifeMax, Three Lake Partners, RohBar in the last 36 months, and Equity in Pliant. NK is also a recipient of a grant from Veracyte and non-financial support from Miragen. All outside the submitted work. In addition, NK has patents on New Therapies in Pulmonary Fibrosis and ARDS (unlicensed) and Peripheral Blood Gene Expression as biomarkers in IPF (licensed to biotech). Not of those are related to the research reported in this manuscript.