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Related Concept Videos

Regulation of Expression at Multiple Steps01:23

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The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
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CLARIFY: cell-cell interaction and gene regulatory network refinement from spatially resolved transcriptomics.

Mihir Bafna1, Hechen Li1, Xiuwei Zhang1

  • 1School of Computational Science and Engineering, College of Computing, Georgia Institute of Technology, Atlanta, GA, 30332, United States.

Bioinformatics (Oxford, England)
|June 30, 2023
PubMed
Summary
This summary is machine-generated.

CLARIFY infers cell-cell interactions (CCIs) and gene regulatory networks (GRNs) simultaneously using spatial transcriptomic data. This novel approach improves the accuracy of both GRN and CCI inference compared to existing methods.

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Area of Science:

  • Computational Biology
  • Systems Biology
  • Genomics

Background:

  • Gene regulatory networks (GRNs) control cellular functions through feedback loops.
  • Cell-cell interactions (CCIs) also influence cellular behavior, especially in spatial contexts.
  • Existing methods often infer GRNs and CCIs in isolation, neglecting their interdependence.

Purpose of the Study:

  • To develop a unified computational model for co-inferring GRNs and CCIs.
  • To leverage spatial transcriptomic data for a more accurate biological network analysis.
  • To introduce a novel tool, CLARIFY, for integrated GRN and CCI inference.

Main Methods:

  • CLARIFY utilizes a multi-level graph autoencoder architecture.
  • The model integrates spatially resolved gene expression data.
  • It refines cell-specific GRNs while inferring CCIs.

Main Results:

  • CLARIFY demonstrated superior performance in inferring both GRNs and CCIs on real and simulated datasets.
  • Co-inference significantly improved accuracy compared to methods inferring GRNs or CCIs separately.
  • The tool was validated on seqFISH and MERFISH spatial transcriptomic data.

Conclusions:

  • Simultaneous inference of GRNs and CCIs is crucial for understanding cellular systems.
  • Layered graph neural networks are effective for analyzing complex biological networks.
  • CLARIFY provides a robust framework for integrated network inference from spatial data.