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Jointly Embedding Multiple Single-Cell Omics Measurements

Authors: Jie Liu, Yuanhao Huang, Ritambhara Singh, Jean-Philippe Vert, and William Stafford Noble

Published in: LIPIcs, Volume 143, 19th International Workshop on Algorithms in Bioinformatics (WABI 2019)


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 in silico 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.

Cite as

Jie Liu, Yuanhao Huang, Ritambhara Singh, Jean-Philippe Vert, and William Stafford Noble. Jointly Embedding Multiple Single-Cell Omics Measurements. In 19th International Workshop on Algorithms in Bioinformatics (WABI 2019). Leibniz International Proceedings in Informatics (LIPIcs), Volume 143, pp. 10:1-10:13, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2019)


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@InProceedings{liu_et_al:LIPIcs.WABI.2019.10,
  author =	{Liu, Jie and Huang, Yuanhao and Singh, Ritambhara and Vert, Jean-Philippe and Noble, William Stafford},
  title =	{{Jointly Embedding Multiple Single-Cell Omics Measurements}},
  booktitle =	{19th International Workshop on Algorithms in Bioinformatics (WABI 2019)},
  pages =	{10:1--10:13},
  series =	{Leibniz International Proceedings in Informatics (LIPIcs)},
  ISBN =	{978-3-95977-123-8},
  ISSN =	{1868-8969},
  year =	{2019},
  volume =	{143},
  editor =	{Huber, Katharina T. and Gusfield, Dan},
  publisher =	{Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
  address =	{Dagstuhl, Germany},
  URL =		{https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2019.10},
  URN =		{urn:nbn:de:0030-drops-110401},
  doi =		{10.4230/LIPIcs.WABI.2019.10},
  annote =	{Keywords: Manifold alignment, single-cell sequencing}
}
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