Abstract
Summary Recent years have seen the release of several toolsets that reveal cell-cell interactions from single-cell data. However, all existing approaches leverage mean celltype gene expression values, and do not preserve the single-cell fidelity of the original data. Here, we present NICHES (Niche Interactions and Communication Heterogeneity in Extracellular Signaling), a tool to explore extracellular signaling at the truly single-cell level. NICHES allows embedding of ligand-receptor signal proxies to visualize heterogeneous signaling archetypes within cell clusters, between cell clusters, and across experimental conditions. When applied to spatial transcriptomic data, NICHES can be used to reflect local cellular microenvironment. NICHES can operate with any list of ligand-receptor signaling mechanisms and is compatible with existing single-cell packages and pseudotime techniques. NICHES is also a user friendly and extensible program, allowing rapid analysis of cell-cell signaling at single-cell resolution.
Availability and implementation NICHES is an open-source software implemented in R under academic free license v3.0 and it is available at github.com/msraredon/NICHES. Use-case vignettes are available at https://msraredon.github.io/NICHES/.
Contact michasam.raredon{at}yale.edu; yuval.kluger{at}yale.edu
Competing Interest Statement
Declaration of Interests MSBR does not declare competing interests. JY does not declare competing interests. NeK does not declare competing interests. WL does not declare competing interests. NK reports personal fees from Boehringer Ingelheim, Third Rock, Pliant, Samumed, NuMedii, Indalo, Theravance, LifeMax, Three Lake Partners, RohBar, and Equity in Pliant. NK is also a recipient of a grant from Veracyte and non-financial support from Miragen. 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). None of those are related to the research reported in this manuscript. LEN is the CEO of Humacyte, Inc, which is a regenerative medicine company. Humacyte produces engineered blood vessels from allogeneic smooth muscle cells for vascular surgery. LEN 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. YK does not declare competing interests.
Footnotes
Revisions to Main Text, Main Figure, Supplement, and Online Materials.