Evidence map›Paper›PMID 42379168›Full record

ArticleCell2026

Systematic discovery of pathogen effector functions across human pathogens and pathways.

Tomas Pachano, He Leng, Guillaume Dugied, Travis Tribble, Vincent Loubiere, Yeojin Lee, Felix Rauh, Victor Manon, Kevin Yuan, Jocelyn Nurtanto and 15 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

25 authors.

Tomas PachanoResearch Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Vienna, Austria.
He LengDonnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario.
Guillaume DugiedDonnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario.
Travis TribbleDonnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
Vincent LoubiereResearch Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Vienna, Austria.
Yeojin LeeCentre for Molecular and Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
Felix RauhResearch Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Vienna, Austria.
Victor ManonHoward Hughes Medical Institute, Chevy Chase, MD, USA; Weill Cornell/Rockefeller/Sloan Kettering Tri-Institutional MD-PhD Program, New York, NY, USA.
Kevin YuanDonnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
Jocelyn NurtantoDepartment of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Centre for Molecular and Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
Alexander SchleifferResearch Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Vienna, Austria.
Veronika YoungInstitute of Network Biology (INET), Molecular Targets and Therapeutics Center (MTTC), Helmholtz Munich, German Research Center for Environmental Health, Neuherberg, Germany.
Benjamin WellerInstitute of Network Biology (INET), Molecular Targets and Therapeutics Center (MTTC), Helmholtz Munich, German Research Center for Environmental Health, Neuherberg, Germany.
Eleanor A LyonsDepartment of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
Matthew R HassCenter for Autoimmune Genomics and Etiology, Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Leah C KottyanCenter for Autoimmune Genomics and Etiology, Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Matthew T WeirauchCenter for Autoimmune Genomics and Etiology, Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Juan I Fuxman BassBiology Department and Bioinformatics Program, Boston University, Boston, MA, USA.
Hayley J NewtonInfection Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, VIC, Australia.
Alexander W EnsmingerDepartment of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Department of Biochemistry, University of Toronto, Toronto, ON, Canada.
Pascal Falter-BraunInstitute of Network Biology (INET), Molecular Targets and Therapeutics Center (MTTC), Helmholtz Munich, German Research Center for Environmental Health, Neuherberg, Germany; Microbe-Host Interactions, Faculty of Biology, Ludwig-Maximilians-Universität (LMU) München, Planegg-Martinsried, Germany.
Jue ChenHoward Hughes Medical Institute, Chevy Chase, MD, USA; Laboratory of Membrane Biophysics and Biology, The Rockefeller University, New York, NY, USA.
Daniel SchramekDepartment of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Centre for Molecular and Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
Alexander StarkResearch Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Vienna, Austria; Medical University of Vienna, Vienna Biocenter (VBC), Vienna, Austria. Electronic address: stark@starklab.org.
Mikko TaipaleDonnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada. Electronic address: mikko.taipale@utoronto.ca.

Funding

Weill Cornell/Rockefeller/Sloan-Kettering MST ProgramT32GM007739 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI HSU, KATHARINE C · 1985 to 2023
$51.1M
HLA GENE COMPLEMENTATION IN PRIMARY SJOGREN'S AND LUPUSR01AI024717 · NIAID · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI KOTTYAN, LEAH CLAIRE, WEIRAUCH, MATTHEW TYSON · 1987 to 2025
$7.8M
Weill Cornell/Rockefeller/Sloan Kettering MST ProgramT32GM152349 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI KATHARINE C HSU · 2024 to 2026
$6.6M
Binding of Epstein Barr Virus EBNA2 Unifies Multiple Sclerosis Genetic MechanismsR01NS099068 · NINDS · CINCINNATI CHILDRENS HOSP MED CTR · PI Leah Claire Kottyan, Matthew Tyson Weirauch · 2017 to 2026
$4.2M
Structure and Function of Immune Gene Regulatory NetworksR35GM128625 · NIGMS · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · PI Juan Ignacio Fuxman Bass · 2018 to 2026
$4.0M
Genomics of Inflammatory Bowel DiseaseR01AI148276 · NIAID · CINCINNATI CHILDRENS HOSP MED CTR · PI KOTTYAN, LEAH CLAIRE · 2019 to 2023
$3.9M
Virus-driven human gene misregulation in diseaseR01HG010730 · NHGRI · CINCINNATI CHILDRENS HOSP MED CTR · PI WEIRAUCH, MATTHEW TYSON · 2020 to 2023
$2.7M
Howard Hughes Medical InstituteNHGRI NIH HHS R01 HG010730NIAID NIH HHS R01 AI024717NIAID NIH HHS R01 AI148276NIGMS NIH HHS R35 GM128625NIGMS NIH HHS T32 GM007739NIGMS NIH HHS T32 GM152349NINDS NIH HHS R01 NS099068
6 · The paper itself

Abstract

Pathogens deploy effector proteins to exploit host cell biology, and most effector open reading frames (ORFs) are rapidly evolving and lack functional annotation. We developed the effector ORFeome (eORFeome), a scalable functional genomics platform encompassing 3,835 effector ORFs from diverse viruses, bacteria, and parasites. High-throughput barcoded screens across nuclear factor κB (NF-κB), apoptosis, p53, cGAS-STING, and major histocompatibility complex class I (MHC class I) pathways revealed novel pathway-modulating functions for hundreds of uncharacterized eORFs, unexpected activities of known effectors, and distinct pathway-specific functions encoded by single ORFs. Illustrating the power of this approach, we identified HHV6A U14 as a p53 antagonist, HHV7 U21 as a dual-function STING antagonist and MHC-I antigen display inhibitor, and adenoviral 13.6K/i-leader protein as a de novo-evolved TAP inhibitor that suppresses MHC-I display. These results establish a general framework for systematic effector annotation, uncover new mechanisms of host-pathogen interaction across kingdoms, and highlight pathogen effectors as a versatile toolkit for rewiring and probing human cellular pathways.

Indexed as

Host-Pathogen InteractionsAnimalscGAS-STING Signaling PathwayGenomicsHumansMembrane ProteinsOpen Reading FramesSignal TransductionSTING ProteinViral ProteinsVirusesMembrane ProteinsSTING1 protein, humanSTING ProteinViral Proteinseffectorsfunctional genomicshigh-throughput screeninghost-pathogen interactionshuman signaling pathwaysORFeomep53pathogensSTINGviral proteins

Identifiers

PMID42379168
PMCPMC13378530

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Registered trials

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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.