PubMed · 2019 · 77 citations · 8 references
Life SciencesBioinformaticsBiologyComputational BiologyGenomicsMulti-omics IntegrationSingle-cell AnalysisSingle-cell GenomicsSingle-cell IntegrationSingle-cell Multi-omics IntegrationSingle-cell Rna Sequencing AnalysisSingle-cell TranscriptomicsChromatin OrganizationIntegration Of Multiple DatasetsIntegration Of Single-cell DatasetsJoint EmbeddingLatent Space EmbeddingLatent Space ModelsSingle-cell Gene Expression ProfilingSingle-cell Omics Integration
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.
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