Title
Jointly embedding multiple single-cell omics measurements
Abstract
Many single-cell sequencing technologies are now available, but it is still difficult to apply multiple sequencing technologies to the same single cell. In this paper, we propose an unsupervised manifold alignment algorithm, MMD-MA, for integrating multiple measurements carried out on disjoint aliquots of a given population of cells. Effectively, MMD-MA performs an co-assay by embedding cells measured in different ways into a learned latent space. In the MMD-MA algorithm, single-cell data points from multiple domains are aligned by optimizing an objective function with three components: (1) a maximum mean discrepancy (MMD) term to encourage the differently measured points to have similar distributions in the latent space, (2) a distortion term to preserve the structure of the data between the input space and the latent space, and (3) a penalty term to avoid collapse to a trivial solution. Notably, MMD-MA does not require any correspondence information across data modalities, either between the cells or between the features. Furthermore, MMD-MA’s weak distributional requirements for the domains to be aligned allow the algorithm to integrate heterogeneous types of single cell measures, such as gene expression, DNA accessibility, chromatin organization, methylation, and imaging data. We demonstrate the utility of MMD-MA in simulation experiments and using a real data set involving single-cell gene expression and methylation data.
Year
DOI
Venue
2019
10.1101/644310
bioRxiv
Keywords
Field
DocType
Applied computing → Computational biology,Computing methodologies → Dimensionality reduction and manifold learning,Computing methodologies → Machine learning algorithms,Computing methodologies → Unsupervised learning,Manifold alignment,single-cell sequencing
Data point,Population,Embedding,Disjoint sets,Pattern recognition,Biology,Manifold alignment,Artificial intelligence,Genetics,Chromatin,Distortion,In silico
Conference
Volume
Citations 
PageRank 
143
0
0.34
References 
Authors
0
5
Name
Order
Citations
PageRank
Jie Liu100.34
Yuanhao Huang200.34
Ritambhara Singh3406.95
Galip Gürkan Yardımcı482.93
William Stafford Noble52907203.56