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MIAMI: mutual information-based analysis of multiplex imaging data.

Souvik Seal1, Debashis Ghosh1

  • 1Department of Biostatistics and Informatics, University of Colorado CU Anschutz Medical Campus, Aurora, CO 80045, USA.

Bioinformatics (Oxford, England)
|June 24, 2022
PubMed
Summary
This summary is machine-generated.

This study introduces a novel method to analyze protein co-expression in cancer, improving risk assessment for survival and recurrence. The method uses mutual information to quantify marker interactions, offering a more robust approach than traditional techniques.

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Area of Science:

  • Computational Biology
  • Cancer Research
  • Bioinformatics

Background:

  • Assessing cancer patient risks like death or recurrence is crucial.
  • Conventional methods for analyzing protein marker co-expression in the tumor microenvironment rely on manual thresholds, which are subjective and lack robustness.
  • This subjectivity is amplified when analyzing multiple markers.

Purpose of the Study:

  • To develop a novel, robust computational method for quantifying protein marker co-expression in cancer.
  • To overcome the limitations of manual thresholding in analyzing complex marker interactions.
  • To provide a more objective and reliable approach for cancer risk assessment.

Main Methods:

  • A new method is presented that treats marker intensities as dependent random variables, using mutual information (MI) as a metric for co-expression.
  • An alternative formulation of MI with an efficient estimation technique is developed, addressing challenges in estimating joint density with increasing numbers of markers.
  • The method was applied to lung cancer and triple-negative breast cancer datasets.

Main Results:

  • Co-expression of HLA-DR and CK markers in lung cancer was associated with patient survival.
  • Co-expression of immuno-regulatory proteins (PD1, PD-L1, Lag3, IDO) in triple-negative breast cancer was linked to disease recurrence.
  • Simulation studies demonstrated the robustness of the proposed method.

Conclusions:

  • The developed method offers a robust and objective approach to analyzing protein marker co-expression in cancer.
  • This quantitative co-expression analysis can improve the assessment of cancer patient risks, including survival and recurrence.
  • The associated R package, MIAMI, is available for broader application in cancer research.