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Multiplexed Analysis of Retinal Gene Expression and Chromatin Accessibility Using scRNA-Seq and scATAC-Seq
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Mapping disease regulatory circuits at cell-type resolution from single-cell multiomics data.

Xi Chen1,2, Yuan Wang3, Antonio Cappuccio4

  • 1Center for Computational Biology, Flatiron Institute, New York, NY, USA.

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|November 17, 2023
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MAGICAL, a new computational method, maps gene regulatory circuits in single cells. It identified sepsis-related circuits in monocytes and epigenetic biomarkers distinguishing MRSA from MSSA infections.

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Area of Science:

  • Genomics
  • Computational Biology
  • Immunology

Background:

  • Understanding gene expression changes in disease requires cell-type resolution.
  • Chromatin remodeling plays a key role in disease pathogenesis.

Purpose of the Study:

  • To develop a computational approach for mapping gene regulatory circuits using multi-omic single-cell data.
  • To apply this method to identify sepsis-associated regulatory circuits and biomarkers.

Main Methods:

  • Developed MAGICAL (Multiome Accessibility Gene Integration Calling and Looping), a hierarchical Bayesian method.
  • Integrated paired single-cell RNA sequencing and single-cell ATAC sequencing data.
  • Applied MAGICAL to peripheral blood mononuclear cells from sepsis patients and controls.

Main Results:

  • MAGICAL accurately inferred regulatory circuits by modeling variations across cells and conditions.
  • Identified sepsis-associated regulatory circuits primarily in CD14 monocytes.
  • Discovered epigenetic circuit biomarkers distinguishing methicillin-resistant *Staphylococcus aureus* (MRSA) from methicillin-susceptible *S. aureus* (MSSA) infections.

Conclusions:

  • MAGICAL provides a powerful framework for dissecting cell-type-specific regulatory mechanisms in disease.
  • The identified biomarkers offer potential for differentiating MRSA from MSSA infections.
  • This approach advances the understanding of host responses to bacterial sepsis.