Spectral Clustering of Single-Cell Multi-Omics Data on Multilayer Graphs

Authors

Shuyi Zhang
Jacob R Leistico
Raymond J Cho
Jeffrey B Cheng
Jun S Song

Language

English

Publication Date

7-11-2022

Journal

Bioinformatics

DOI

10.1093/bioinformatics/btac378

PMID

35652725

PMCID

PMC9272806

PubMedCentral® Posted Date

6-2-2022

PubMedCentral® Full Text Version

Post-print

Abstract

Motivation: Single-cell sequencing technologies that simultaneously generate multimodal cellular profiles present opportunities for improved understanding of cell heterogeneity in tissues. How the multimodal information can be integrated to obtain a common cell type identification, however, poses a computational challenge. Multilayer graphs provide a natural representation of multi-omic single-cell sequencing datasets, and finding cell clusters may be understood as a multilayer graph partition problem.

Results: We introduce two spectral algorithms on multilayer graphs, spectral clustering on multilayer graphs and the weighted locally linear (WLL) method, to cluster cells in multi-omic single-cell sequencing datasets. We connect these algorithms through a unifying mathematical framework that represents each layer using a Hamiltonian operator and a mixture of its eigenstates to integrate the multiple graph layers, demonstrating in the process that the WLL method is a rigorous multilayer spectral graph theoretic reformulation of the popular Seurat weighted nearest neighbor (WNN) algorithm. Implementing our algorithms and applying them to a CITE-seq dataset of cord blood mononuclear cells yields results similar to the Seurat WNN analysis. Our work thus extends spectral methods to multimodal single-cell data analysis.

Availability and implementation: The code used in this study can be found at https://github.com/jssong-lab/sc-spectrum. All public data used in the article are accurately cited and described in Materials and Methods and in Supplementary Information.

Supplementary information: Supplementary data are available at Bioinformatics online.

Keywords

Cluster Analysis, Single-Cell Analysis, Sequence Analysis, RNA, Algorithms

Published Open-Access

yes

Recommended Citation

Zhang, Shuyi; Leistico, Jacob R; Cho, Raymond J; et al., "Spectral Clustering of Single-Cell Multi-Omics Data on Multilayer Graphs" (2022). Staff and Researcher Publications. 21.
https://digitalcommons.library.tmc.edu/clinic_pub/21