Deciphering the combinatorial landscape of immunity
From cellular activation to drug combinations, immunological responses are shaped by the action of multiple stimuli. Synergistic and antagonistic interactions between stimuli play major roles in shaping immune processes. To understand combinatorial regulation, we present the immune Synergistic/Antag...
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doaj-efedfbd913d2485c91ef4e73cbbc316d2021-05-05T21:44:59ZengeLife Sciences Publications LtdeLife2050-084X2020-11-01910.7554/eLife.62148Deciphering the combinatorial landscape of immunityAntonio Cappuccio0Shane T Jensen1Boris M Hartmann2https://orcid.org/0000-0002-5649-6776Stuart C Sealfon3Vassili Soumelis4Elena Zaslavsky5https://orcid.org/0000-0002-4828-7771Institut Curie, Integrative Biology of Human Dendritic Cells and T Cells Laboratory, PSL Research University, Inserm, U932, Paris, France; Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, United StatesDepartment of Statistics, Wharton School, University of Pennsylvania, Philadelphia, United StatesDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, United StatesDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, United StatesInstitut Curie, Integrative Biology of Human Dendritic Cells and T Cells Laboratory, PSL Research University, Inserm, U932, Paris, France; Laboratoire d'immunologie, biologie et histocompatibilité, AP-HP, Hôpital Saint-Louis, Paris, FranceDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, United StatesFrom cellular activation to drug combinations, immunological responses are shaped by the action of multiple stimuli. Synergistic and antagonistic interactions between stimuli play major roles in shaping immune processes. To understand combinatorial regulation, we present the immune Synergistic/Antagonistic Interaction Learner (iSAIL). iSAIL includes a machine learning classifier to map and interpret interactions, a curated compendium of immunological combination treatment datasets, and their global integration into a landscape of ~30,000 interactions. The landscape is mined to reveal combinatorial control of interleukins, checkpoints, and other immune modulators. The resource helps elucidate the modulation of a stimulus by interactions with other cofactors, showing that TNF has strikingly different effects depending on co-stimulators. We discover new functional synergies between TNF and IFNβ controlling dendritic cell-T cell crosstalk. Analysis of laboratory or public combination treatment studies with this user-friendly web-based resource will help resolve the complex role of interaction effects on immune processes.https://elifesciences.org/articles/62148combination treatment experimentcytokine interactionssynergy antagonismdendritic cell T cell cross-talkmachine learningsignal integration |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Antonio Cappuccio Shane T Jensen Boris M Hartmann Stuart C Sealfon Vassili Soumelis Elena Zaslavsky |
spellingShingle |
Antonio Cappuccio Shane T Jensen Boris M Hartmann Stuart C Sealfon Vassili Soumelis Elena Zaslavsky Deciphering the combinatorial landscape of immunity eLife combination treatment experiment cytokine interactions synergy antagonism dendritic cell T cell cross-talk machine learning signal integration |
author_facet |
Antonio Cappuccio Shane T Jensen Boris M Hartmann Stuart C Sealfon Vassili Soumelis Elena Zaslavsky |
author_sort |
Antonio Cappuccio |
title |
Deciphering the combinatorial landscape of immunity |
title_short |
Deciphering the combinatorial landscape of immunity |
title_full |
Deciphering the combinatorial landscape of immunity |
title_fullStr |
Deciphering the combinatorial landscape of immunity |
title_full_unstemmed |
Deciphering the combinatorial landscape of immunity |
title_sort |
deciphering the combinatorial landscape of immunity |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2020-11-01 |
description |
From cellular activation to drug combinations, immunological responses are shaped by the action of multiple stimuli. Synergistic and antagonistic interactions between stimuli play major roles in shaping immune processes. To understand combinatorial regulation, we present the immune Synergistic/Antagonistic Interaction Learner (iSAIL). iSAIL includes a machine learning classifier to map and interpret interactions, a curated compendium of immunological combination treatment datasets, and their global integration into a landscape of ~30,000 interactions. The landscape is mined to reveal combinatorial control of interleukins, checkpoints, and other immune modulators. The resource helps elucidate the modulation of a stimulus by interactions with other cofactors, showing that TNF has strikingly different effects depending on co-stimulators. We discover new functional synergies between TNF and IFNβ controlling dendritic cell-T cell crosstalk. Analysis of laboratory or public combination treatment studies with this user-friendly web-based resource will help resolve the complex role of interaction effects on immune processes. |
topic |
combination treatment experiment cytokine interactions synergy antagonism dendritic cell T cell cross-talk machine learning signal integration |
url |
https://elifesciences.org/articles/62148 |
work_keys_str_mv |
AT antoniocappuccio decipheringthecombinatoriallandscapeofimmunity AT shanetjensen decipheringthecombinatoriallandscapeofimmunity AT borismhartmann decipheringthecombinatoriallandscapeofimmunity AT stuartcsealfon decipheringthecombinatoriallandscapeofimmunity AT vassilisoumelis decipheringthecombinatoriallandscapeofimmunity AT elenazaslavsky decipheringthecombinatoriallandscapeofimmunity |
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