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Related Experiment Video

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DITHER: an algorithm for Defining IntraTumor Heterogeneity based on EntRopy.

Lin Li1, Canping Chen1, Xiaosheng Wang1

  • 1Biomedical Informatics Research Lab, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China.

Briefings in Bioinformatics
|June 7, 2021
PubMed
Summary

We developed the DITHER algorithm to measure intratumor heterogeneity (ITH), finding it strongly correlates with tumor progression and immune evasion. DITHER offers a more robust ITH evaluation compared to existing methods.

Keywords:
algorithmcopy number alterationsentropygenomic instabilityintratumor heterogeneitysomatic mutationstumor immune evasion

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Area of Science:

  • Oncology
  • Genomics
  • Computational Biology

Background:

  • Intratumor heterogeneity (ITH) significantly impacts tumor development, patient prognosis, immune evasion, and treatment response.
  • Accurate quantification of ITH is crucial for understanding tumor biology and guiding clinical decisions.

Purpose of the Study:

  • To introduce and validate the Defining ITH based on EntRopy (DITHER) algorithm for evaluating ITH.
  • To compare DITHER's performance against existing ITH assessment methods.

Main Methods:

  • Calculated tumor ITH by averaging the entropies of somatic mutation and copy number alteration (CNA) profiles.
  • Applied the DITHER algorithm to analyze 33 cancer types from The Cancer Genome Atlas (TCGA).
  • Compared DITHER with MATH and PhyloWGS for ITH evaluation.

Main Results:

  • DITHER-defined ITH demonstrated strong correlations with tumor progression, unfavorable phenotypes, genomic instability, and immune evasion.
  • DITHER showed superior performance in capturing ITH characteristics compared to MATH and PhyloWGS.
  • DITHER scores positively correlated with tumor purity, indicating a focus on inter-tumor cell heterogeneity.
  • Microsatellite instability-high (MSI-high) tumors exhibited lower DITHER scores than microsatellite stability (MSS)/MSI-low tumors, suggesting homogeneous hypermutation within MSI tumors.

Conclusions:

  • The DITHER algorithm provides a robust and comprehensive method for quantifying ITH.
  • DITHER's findings offer new insights into tumor biology, particularly regarding MSI tumors and inter-tumor cell heterogeneity.
  • DITHER holds potential for advancing clinical applications in cancer research and treatment.