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DOI: 10.4230/LIPIcs.WABI.2019.10

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.

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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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DOI: 10.4230/LIPIcs.WABI.2019.11

Inferring Diploid 3D Chromatin Structures from Hi-C Data

Authors: Alexandra Gesine Cauer, Gürkan Yardımcı, Jean-Philippe Vert, Nelle Varoquaux, and William Stafford Noble

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

Abstract

The 3D organization of the genome plays a key role in many cellular processes, such as gene regulation, differentiation, and replication. Assays like Hi-C measure DNA-DNA contacts in a high-throughput fashion, and inferring accurate 3D models of chromosomes can yield insights hidden in the raw data. For example, structural inference can account for noise in the data, disambiguate the distinct structures of homologous chromosomes, orient genomic regions relative to nuclear landmarks, and serve as a framework for integrating other data types. Although many methods exist to infer the 3D structure of haploid genomes, inferring a diploid structure from Hi-C data is still an open problem. Indeed, the diploid case is very challenging, because Hi-C data typically does not distinguish between homologous chromosomes. We propose a method to infer 3D diploid genomes from Hi-C data. We demonstrate the accuracy of the method on simulated data, and we also use the method to infer 3D structures for mouse chromosome X, confirming that the active homolog exhibits a bipartite structure, whereas the active homolog does not.

Cite as

Alexandra Gesine Cauer, Gürkan Yardımcı, Jean-Philippe Vert, Nelle Varoquaux, and William Stafford Noble. Inferring Diploid 3D Chromatin Structures from Hi-C Data. In 19th International Workshop on Algorithms in Bioinformatics (WABI 2019). Leibniz International Proceedings in Informatics (LIPIcs), Volume 143, pp. 11:1-11:13, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2019)

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@InProceedings{cauer_et_al:LIPIcs.WABI.2019.11,
  author =	{Cauer, Alexandra Gesine and Yard{\i}mc{\i}, G\"{u}rkan and Vert, Jean-Philippe and Varoquaux, Nelle and Noble, William Stafford},
  title =	{{Inferring Diploid 3D Chromatin Structures from Hi-C Data}},
  booktitle =	{19th International Workshop on Algorithms in Bioinformatics (WABI 2019)},
  pages =	{11:1--11:13},
  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.2019.11},
  URN =		{urn:nbn:de:0030-drops-110418},
  doi =		{10.4230/LIPIcs.WABI.2019.11},
  annote =	{Keywords: Genome 3D architecture, chromatin structure, Hi-C, 3D modeling}
}

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Documents authored by Noble, William Stafford

Jointly Embedding Multiple Single-Cell Omics Measurements

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Inferring Diploid 3D Chromatin Structures from Hi-C Data

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