ArticleFrontiers in immunology2019
A Modular Cytokine Analysis Method Reveals Novel Associations With Clinical Phenotypes and Identifies Sets of Co-signaling Cytokines Across Influenza Natural Infection Cohorts and Healthy Controls.
Article in Frontiers in immunology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed.
- Cytokine Profiles and Antibody Response Associated to Choclo Orthohantavirus Infection.Frontiers in immunology · 2021Trial
- Dupilumab Dampens Mucosal Type 2 Response During Acetylsalicylic Acid Challenge in N-ERD Patients.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2026Article
- Human Systems Immunology in the Omics Era: Challenges, Methods, and Emerging Directions.European journal of immunology · 2026Review
- Persistent Immune Dysregulation during Long COVID is Manifested in Antibodies Targeting Envelope and Nucleocapsid Proteins.Research square · 2026Article
- Dynamic monitoring of a core pro-inflammatory cytokine panel improves mortality prediction in severe influenza.Frontiers in immunology · 2026Article
- Persistent Immune Dysregulation during Post-Acute Sequelae of COVID-19 is Manifested in Antibodies Targeting Envelope and Nucleocapsid Proteins.bioRxiv : the preprint server for biology · 2025Article
- ZBP1-driven cell death in severe influenza.Trends in microbiology · 2025Review
- Modeling the response to interleukin-21 to inform natural killer cell immunotherapy.Immunology and cell biology · 2025Article
- Small extracellular vesicles in plasma carry luminal cytokines that remain undetectable by antibody-based assays in cancer patients and healthy donors.BJC reports · 2024Article
- Article
- Systems biology analysis reveals distinct molecular signatures associated with immune responsiveness to the BNT162b COVID-19 vaccine.EBioMedicine · 2024Article
- Effects of repeated binge intake of the pyrovalerone cathinone derivative 3,4-methylenedioxypyrovalerone on prefrontal cytokine levels in rats - a preliminary study.Frontiers in behavioral neuroscience · 2023Article
- Biomarkers of Airway Immune Homeostasis Differ Significantly with Generation of E-Cigarettes.American journal of respiratory and critical care medicine · 2022Article
- Hydrolytically Degradable Microgels with Tunable Mechanical Properties Modulate the Host Immune Response.Small (Weinheim an der Bergstrasse, Germany) · 2022Article
- The tumor and plasma cytokine profiles of renal cell carcinoma patients.Scientific reports · 2022Article
- Cytokine signature clusters as a tool to compare changes associated with tobacco product use in upper and lower airway samples.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- Brain-immune axis regulation is responsive to cognitive behavioral therapy and mindfulness intervention: Observations from a randomized controlled trial in patients with Crohn's disease.Brain, behavior, & immunity - health · 2022Article
- Decreased IL-10 accelerates B-cell leukemia/lymphoma in a mouse model of pediatric lymphoid leukemia.Blood advances · 2022Article
- Standardized Whole Blood Assay and Bead-Based Cytokine Profiling Reveal Commonalities and Diversity of the Response to Bacteria and TLR Ligands in Cattle.Frontiers in immunology · 2022Article
- Ontogeny of plasma cytokine and chemokine concentrations across the first week of human life.Cytokine · 2021Article
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Authors and funding
12 authors.
Funding
Abstract
Cytokines and chemokines are key signaling molecules of the immune system. Recent technological advances enable measurement of multiplexed cytokine profiles in biological samples. These profiles can then be used to identify potential biomarkers of a variety of clinical phenotypes. However, testing for such associations for each cytokine separately ignores the highly context-dependent covariation in cytokine secretion and decreases statistical power to detect associations due to multiple hypothesis testing. Here we present CytoMod-a novel data-driven approach for analysis of cytokine profiles that uses unsupervised clustering and regression to identify putative functional modules of co-signaling cytokines. Each module represents a biosignature of co-signaling cytokines. We applied this approach to three independent clinical cohorts of subjects naturally infected with influenza in which cytokine profiles and clinical phenotypes were collected. We found that in two out of three cohorts, cytokine modules were significantly associated with clinical phenotypes, and in many cases these associations were stronger than the associations of the individual cytokines within them. By comparing cytokine modules across datasets, we identified cytokine "cores"-specific subsets of co-expressed cytokines that clustered together across the three cohorts. Cytokine cores were also associated with clinical phenotypes. Interestingly, most of these cores were also co-expressed in a cohort of healthy controls, suggesting that in part, patterns of cytokine co-signaling may be generalizable. CytoMod can be readily applied to any cytokine profile dataset regardless of measurement technology, increases the statistical power to detect associations with clinical phenotypes and may help shed light on the complex co-signaling networks of cytokines in both health and infection.
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