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T and B Cell Receptor Immune Repertoire Analysis using Next-generation Sequencing
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Deciphering the combinatorial landscape of immunity.

Antonio Cappuccio1,2, Shane T Jensen3, Boris M Hartmann2

  • 1Institut Curie, Integrative Biology of Human Dendritic Cells and T Cells Laboratory, PSL Research University, Inserm, U932, Paris, France.

Elife
|November 23, 2020
PubMed
Summary

We developed the immune Synergistic/Antagonistic Interaction Learner (iSAIL) to map how multiple stimuli interact in immune responses. iSAIL reveals complex combinatorial effects on immune modulators and uncovers new synergies, aiding research into immune interactions.

Keywords:
combination treatment experimentcomputational biologycytokine interactionsdendritic cell T cell cross-talkhumanimmunologyinflammationmachine learningmousesignal integrationsynergy antagonismsystems biology

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Area of Science:

  • Immunology
  • Computational Biology
  • Bioinformatics

Background:

  • Immune responses are regulated by complex interactions between multiple stimuli.
  • Understanding synergistic and antagonistic effects is crucial for deciphering immune processes and developing effective therapies.

Purpose of the Study:

  • To develop a machine learning tool, the immune Synergistic/Antagonistic Interaction Learner (iSAIL), for mapping and interpreting interactions between immunological stimuli.
  • To create a comprehensive resource integrating diverse immunological combination treatment datasets.

Main Methods:

  • Developed a machine learning classifier to analyze interactions between immunological stimuli.
  • Curated and integrated a compendium of approximately 30,000 immunological combination treatment datasets.
  • Analyzed the integrated landscape to identify combinatorial control of immune modulators.

Main Results:

  • The iSAIL resource provides a landscape of ~30,000 interactions, revealing combinatorial control of interleukins, checkpoints, and other immune modulators.
  • Demonstrated that tumor necrosis factor (TNF) exhibits varied effects based on co-stimulators.
  • Discovered novel functional synergies between TNF and interferon-beta (IFNβ) in regulating dendritic cell-T cell crosstalk.

Conclusions:

  • iSAIL facilitates the elucidation of how cofactors modulate individual stimuli within complex immune interactions.
  • This user-friendly web-based resource aids in resolving the intricate roles of interaction effects in immunological studies.
  • The findings highlight the importance of considering combinatorial effects in immune modulation and therapeutic strategies.