Evidence map›Paper›PMID 34127431›Full record

ArticleEBioMedicine2021

AI-guided discovery of the invariant host response to viral pandemics.

Debashis Sahoo, Gajanan D Katkar, Soni Khandelwal, Mahdi Behroozikhah, Amanraj Claire, Vanessa Castillo, Courtney Tindle, MacKenzie Fuller, Sahar Taheri, Thomas F Rogers and 12 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in EBioMedicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
3.0field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

25 citing papers in PubMed, 53 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Article
  6. Artificial intelligence-guided discovery of gastric cancer continuum.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2023
    Article
  7. Article
  8. Review
  9. Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2022
    Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Review
  18. Natural killer cells in antiviral immunity.Nature reviews. Immunology · 2022
    Review
  19. Review
  20. Experimental and therapeutic medicine · 2022
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors at 4 institutions in 1 country.

Debashis SahooDepartment of Pediatrics, University of California San Diego, 9500 Gilman Drive, MC 0730, Leichtag Building 132, La Jolla, CA 92093-0831, USA; Department of Computer Science and Engineering, Jacobs School of Engineering, University of California San Diego, USA; Moores Cancer Center, University of California San Diego, USA. Electronic address: dsahoo@ucsd.edu.
Gajanan D KatkarDepartment of Cellular and Molecular Medicine, University of California San Diego, USA.
Soni KhandelwalDepartment of Pediatrics, University of California San Diego, 9500 Gilman Drive, MC 0730, Leichtag Building 132, La Jolla, CA 92093-0831, USA.
Mahdi BehroozikhahDepartment of Computer Science and Engineering, Jacobs School of Engineering, University of California San Diego, USA.
Amanraj ClaireDepartment of Cellular and Molecular Medicine, University of California San Diego, USA.
Vanessa CastilloDepartment of Cellular and Molecular Medicine, University of California San Diego, USA.
Courtney TindleDepartment of Cellular and Molecular Medicine, University of California San Diego, USA.
MacKenzie FullerDepartment of Cellular and Molecular Medicine, University of California San Diego, USA.
Sahar TaheriDepartment of Computer Science and Engineering, Jacobs School of Engineering, University of California San Diego, USA.
Thomas F RogersDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; Division of Infectious Diseases, Department of Medicine, University of California, San Diego, La Jolla, CA 92037, USA.
Nathan BeutlerDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Sydney I RamirezCenter for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA, USA; Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego (UCSD), La Jolla, CA, USA.
Stephen A RawlingsDepartment of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego (UCSD), La Jolla, CA, USA.
Victor PretoriusDepartment of Surgery, University of California San Diego, USA.
Davey M SmithDepartment of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego (UCSD), La Jolla, CA, USA.
Dennis R BurtonDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
Laura E Crotty AlexanderPulmonary Critical Care Section, Veterans Affairs (VA) San Diego Healthcare System, La Jolla, California; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California San Diego (UCSD), La Jolla, CA, USA.
Jason DuranDivision of Cardiology, Department of Internal Medicine, UC San Diego Medical Center, La Jolla 92037.
Shane CrottyCenter for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA, USA; Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego (UCSD), La Jolla, CA, USA.
Jennifer M DanCenter for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA, USA; Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego (UCSD), La Jolla, CA, USA.
Soumita DasDepartment of Pathology, University of California San Diego, USA. Electronic address: sodas@ucsd.edu.
Pradipta GhoshMoores Cancer Center, University of California San Diego, USA; Department of Cellular and Molecular Medicine, University of California San Diego, USA; Medicine, University of California San Diego, USA. Electronic address: prghosh@ucsd.edu.
University of California San Diego · USLa Jolla Institute for Immunology · USScripps Research Institute · USUniversity of San Diego · US

Funding

Macrophage Polarization in Response to Infections and InflammationR01AI155696 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GHOSH, PRADIPTA, SAHOO, DEBASHIS · 2020 to 2024
$4.9M
UC San Diego RAPID Faculty Development Program in Infectious DiseasesR25AI147376 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ADRIANA H TREMOULET, Joann Trejo · 2020 to 2026
$2.5M
Innate responses following infection with enteric microbesR01DK107585 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DAS, SOUMITA · 2016 to 2020
$2.2M
Summer Student Research on the Application of Boolean AnalysisR01GM138385 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SAHOO, DEBASHIS · 2020 to 2023
$2.0M
Precision therapeutics of inflammatory bowel disease guided by Boolean logicUG3TR003355 · NCATS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DAS, SOUMITA, GHOSH, PRADIPTA · 2020 to 2022
$937k
NCATS NIH HHS UG3 TR003355NIAID NIH HHS R01 AI155696NIAID NIH HHS R25 AI147376NIDDK NIH HHS R01 DK107585NIGMS NIH HHS R01 GM138385
6 · The paper itself

Abstract

backgroundCoronavirus Disease 2019 (Covid-19) continues to challenge the limits of our knowledge and our healthcare system. Here we sought to define the host immune response, a.k.a, the "cytokine storm" that has been implicated in fatal COVID-19 using an AI-based approach.

methodOver 45,000 transcriptomic datasets of viral pandemics were analyzed to extract a 166-gene signature using ACE2 as a 'seed' gene; ACE2 was rationalized because it encodes the receptor that facilitates the entry of SARS-CoV-2 (the virus that causes COVID-19) into host cells. An AI-based approach was used to explore the utility of the signature in navigating the uncharted territory of Covid-19, setting therapeutic goals, and finding therapeutic solutions.

findingsThe 166-gene signature was surprisingly conserved across all viral pandemics, including COVID-19, and a subset of 20-genes classified disease severity, inspiring the nomenclatures ViP and severe-ViP signatures, respectively. The ViP signatures pinpointed a paradoxical phenomenon wherein lung epithelial and myeloid cells mount an IL15 cytokine storm, and epithelial and NK cell senescence and apoptosis determine severity/fatality. Precise therapeutic goals could be formulated; these goals were met in high-dose SARS-CoV-2-challenged hamsters using either neutralizing antibodies that abrogate SARS-CoV-2•ACE2 engagement or a directly acting antiviral agent, EIDD-2801. IL15/IL15RA were elevated in the lungs of patients with fatal disease, and plasma levels of the cytokine prognosticated disease severity.

interpretationThe ViP signatures provide a quantitative and qualitative framework for titrating the immune response in viral pandemics and may serve as a powerful unbiased tool to rapidly assess disease severity and vet candidate drugs.

fundingThis work was supported by the National Institutes for Health (NIH) [grants CA151673 and GM138385 (to DS) and AI141630 (to P.G), DK107585-05S1 (SD) and AI155696 (to P.G, D.S and S.D), U19-AI142742 (to S. C, CCHI: Cooperative Centers for Human Immunology)]; Research Grants Program Office (RGPO) from the University of California Office of the President (UCOP) (R00RG2628 & R00RG2642 to P.G, D.S and S.D); the UC San Diego Sanford Stem Cell Clinical Center (to P.G, D.S and S.D); LJI Institutional Funds (to S.C); the VA San Diego Healthcare System Institutional funds (to L.C.A). GDK was supported through The American Association of Immunologists Intersect Fellowship Program for Computational Scientists and Immunologists. ONE SENTENCE SUMMARY: The host immune response in COVID-19.

Indexed as

Angiotensin-Converting Enzyme 2AnimalsAntibodies, NeutralizingAntiviral AgentsArtificial IntelligenceAutopsyCOVID-19COVID-19 Drug TreatmentCricetinaeCytidineDatabases, GeneticDisease Models, AnimalGene Expression ProfilingGene Regulatory NetworksGenetic MarkersHumansACE2 protein, humanAngiotensin-Converting Enzyme 2Antibodies, NeutralizingAntiviral AgentsCytidineGenetic MarkersHydroxylaminesIL15 protein, humanIL15RA protein, humanInterleukin-15molnupiravirReceptors, Interleukin-15Angiotensin converting enzyme (ACE)-2Artificial intelligence/machine learningBoolean equivalent clustersCoronavirus COVID-19Immune responseInterleukin 15 (IL15)Lung alveoliNatural Killer (NK) cells

Identifiers

PMID34127431
PMCPMC8193764
OpenAlexW3168114461

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.