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SPaRTAN, a computational framework for linking cell-surface receptors to transcriptional regulators

Xiaojun Ma, Ashwin Somasundaram, Zengbiao Qi, Harinder Singh, View ORCID ProfileHatice Ulku Osmanbeyoglu
doi: https://doi.org/10.1101/2020.12.22.423961
Xiaojun Ma
1Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, PA, USA
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Ashwin Somasundaram
2Department of Medicine, Division of Hematology/Oncology, University of Pittsburgh, Pittsburgh, PA, USA
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Zengbiao Qi
1Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, PA, USA
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Harinder Singh
3Center for Systems Immunology and Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA
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Hatice Ulku Osmanbeyoglu
1Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, PA, USA
4Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA
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  • ORCID record for Hatice Ulku Osmanbeyoglu
  • For correspondence: osmanbeyogluhu@pitt.edu
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Abstract

The developmental pathways and functions of specialized cell types are dependent on the complex interplay between signaling and transcriptional networks. We present SPaRTAN (Single-cell Proteomic and RNA based Transcription factor Activity Network), a computational method to link cell-surface receptors to transcription factors (TFs) by exploiting cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) datasets with cis-regulatory information. SPaRTAN is applied to peripheral blood mononuclear cells (PBMCs) to predict the coupling of signaling receptors with cell context-specific TF activities. The predictions are validated by flow cytometry analyses. SPaRTAN is then used to analyze the signaling coupled TF activity states of tumor infiltrating CD8+ T cells in malignant peritoneal and pleural mesotheliomas. SPaRTAN greatly enhances the utility of CITE-seq datasets to probe signaling coupled TF networks that regulate developmental or functional transitions in cellular states.

Competing Interest Statement

The authors have declared no competing interest.

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 December 22, 2020.
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SPaRTAN, a computational framework for linking cell-surface receptors to transcriptional regulators
Xiaojun Ma, Ashwin Somasundaram, Zengbiao Qi, Harinder Singh, Hatice Ulku Osmanbeyoglu
bioRxiv 2020.12.22.423961; doi: https://doi.org/10.1101/2020.12.22.423961
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SPaRTAN, a computational framework for linking cell-surface receptors to transcriptional regulators
Xiaojun Ma, Ashwin Somasundaram, Zengbiao Qi, Harinder Singh, Hatice Ulku Osmanbeyoglu
bioRxiv 2020.12.22.423961; doi: https://doi.org/10.1101/2020.12.22.423961

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