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TEA-seq: a trimodal assay for integrated single cell measurement of transcription, epitopes, and chromatin accessibility

View ORCID ProfileElliott Swanson, View ORCID ProfileCara Lord, View ORCID ProfileJulian Reading, View ORCID ProfileAlexander T. Heubeck, View ORCID ProfileAdam K. Savage, View ORCID ProfileRichard Green, Xiao-jun Li, View ORCID ProfileTroy R. Torgerson, Thomas F. Bumol, View ORCID ProfileLucas T. Graybuck, View ORCID ProfilePeter J. Skene
doi: https://doi.org/10.1101/2020.09.04.283887
Elliott Swanson
1Allen Institute for Immunology, Seattle, WA, USA
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Cara Lord
1Allen Institute for Immunology, Seattle, WA, USA
2GlaxoSmithKline, Collegeville, PA, USA
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Julian Reading
1Allen Institute for Immunology, Seattle, WA, USA
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Alexander T. Heubeck
1Allen Institute for Immunology, Seattle, WA, USA
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Adam K. Savage
1Allen Institute for Immunology, Seattle, WA, USA
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Richard Green
1Allen Institute for Immunology, Seattle, WA, USA
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Xiao-jun Li
1Allen Institute for Immunology, Seattle, WA, USA
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Troy R. Torgerson
1Allen Institute for Immunology, Seattle, WA, USA
3Department of Pediatrics, University of Washington, Seattle, WA, USA
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Thomas F. Bumol
1Allen Institute for Immunology, Seattle, WA, USA
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Lucas T. Graybuck
1Allen Institute for Immunology, Seattle, WA, USA
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Peter J. Skene
1Allen Institute for Immunology, Seattle, WA, USA
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  • For correspondence: peter.skene@alleninstitute.org
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Abstract

Single-cell measurements of cellular characteristics have been instrumental in understanding the heterogeneous pathways that drive differentiation, cellular responses to extracellular signals, and human disease states. scATAC-seq has been particularly challenging due to the large size of the human genome and processing artefacts resulting from DNA damage that are an inherent source of background signal. Downstream analysis and integration of scATAC-seq with other single-cell assays is complicated by the lack of clear phenotypic information linking chromatin state and cell type. Using the heterogeneous mixture of cells in human peripheral blood as a test case, we developed a novel scATAC-seq workflow that increases the signal-to-noise ratio and allows simultaneous measurement of cell surface markers: Integrated Cellular Indexing of Chromatin Landscape and Epitopes (ICICLE-seq). We extended this approach using a droplet-based multiomics platform to develop a trimodal assay to simultaneously measure Transcriptomic state (scRNA-seq), cell surface Epitopes, and chromatin Accessibility (scATAC-seq) from thousands of single cells, which we term TEA-seq. Together, these multimodal single-cell assays provide a novel toolkit to identify type-specific gene regulation and expression grounded in phenotypically defined cell types.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Revision 2020-11-16: added TEA-seq results, methods, and discussion; Updated title and text throughout to include this new method.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted November 16, 2020.
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TEA-seq: a trimodal assay for integrated single cell measurement of transcription, epitopes, and chromatin accessibility
Elliott Swanson, Cara Lord, Julian Reading, Alexander T. Heubeck, Adam K. Savage, Richard Green, Xiao-jun Li, Troy R. Torgerson, Thomas F. Bumol, Lucas T. Graybuck, Peter J. Skene
bioRxiv 2020.09.04.283887; doi: https://doi.org/10.1101/2020.09.04.283887
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TEA-seq: a trimodal assay for integrated single cell measurement of transcription, epitopes, and chromatin accessibility
Elliott Swanson, Cara Lord, Julian Reading, Alexander T. Heubeck, Adam K. Savage, Richard Green, Xiao-jun Li, Troy R. Torgerson, Thomas F. Bumol, Lucas T. Graybuck, Peter J. Skene
bioRxiv 2020.09.04.283887; doi: https://doi.org/10.1101/2020.09.04.283887

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