Better explicating the strengths and shortcomings of these models will help refine projections and improve transparency in the years ahead.
Image credit: Witsawat.S.
Contributed by Wing Hung Wong, June 14, 2018 (sent for review April 4, 2018; reviewed by Andrew D. Smith and Nancy R. Zhang)
Significance
Biological samples are often heterogeneous mixtures of different types of cells. Suppose we have two single-cell datasets, each providing information on a different cellular feature and generated on a different sample from this mixture. Then, the clustering of cells in the two samples should be coupled as both clusterings are reflecting the underlying cell types in the same mixture. This “coupled clustering” problem is a new problem not covered by existing clustering methods. In this paper, we develop an approach for its solution based on the coupling of two nonnegative matrix factorizations. The method should be useful for integrative single-cell genomics analysis tasks such as the joint analysis of single-cell RNA-sequencing and single-cell ATAC-sequencing data.
Abstract
When different types of functional genomics data are generated on single cells from different samples of cells from the same heterogeneous population, the clustering of cells in the different samples should be coupled. We formulate this “coupled clustering” problem as an optimization problem and propose the method of coupled nonnegative matrix factorizations (coupled NMF) for its solution. The method is illustrated by the integrative analysis of single-cell RNA-sequencing (RNA-seq) and single-cell ATAC-sequencing (ATAC-seq) data.
Footnotes
↵1Z.D., X.C., and M.Z. contributed equally to this work.
- ↵2To whom correspondence should be addressed. Email: whwong{at}stanford.edu.
Author contributions: H.Y.C., Y.W., and W.H.W. designed research; Z.D., X.C., W.Z., and A.T.S. performed research; Z.D., M.Z., and W.H.W. analyzed data; and Z.D., M.Z., and W.H.W. wrote the paper.
Reviewers: A.D.S., University of Southern California; and N.R.Z., University of Pennsylvania.
The authors declare no conflict of interest.
Data deposition: The single- cell gene expression data and chromatin accessibility data of RA induction reported in this paper have been deposited in the Gene Expression Omnibus (GEO) database, https://www.ncbi.nlm.nih.gov/geo (accession nos. GSE115968 and GSE115970).
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1805681115/-/DCSupplemental.
- Copyright © 2018 the Author(s). Published by PNAS.
This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).
Integrative analysis of single-cell genomics data by coupled nonnegative matrix factorizations
Article Classifications
- Physical Sciences
- Statistics
- Biological Sciences
- Genetics
Sign up for Article Alerts
Jump to section
You May Also be Interested in
Did the Caribbean sweep into the western Amazon millions of years ago, shaping the region’s rich biodiversity?
Image credit: Tacio Cordeiro Bicudo (University of São Paulo, São Paulo, Brazil), Victor Sacek (University of São Paulo, São Paulo, Brazil), and Lucy Reading-Ikkanda (artist).
Settlements 4,200 years ago may have suffered from overpopulation before drought and lower temperatures ultimately made them unsustainable.
Image credit: Andrea Ricci.
Mara Reed and Michael Manga explore why Yellowstone's Steamboat Geyser resumed erupting in 2018.
Some songbird parents might improve their own fitness by manipulating their offspring into leaving the nest early, at the cost of fledgling survival, a study finds.
Image credit: Gil Eckrich (photographer).