Machine learning assisted immune profiling of COPD identifies a unique emphysema subtype independent of GOLD stage
Summary: Chronic obstructive pulmonary disease (COPD) is a severe, progressive, and heterogeneous disease with a poor outcome. Inflammation plays a central role in disease pathogenesis; however, the interplay between immune changes and disease heterogeneity has been difficult to unravel. We performe...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-07-01
|
| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225012271 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849415119972335616 |
|---|---|
| author | Natalie Bordag Katharina Jandl Ayu Hutami Syarif Jürgen Gindlhuber Diana Schnoegl Ayse Ceren Mutgan Vasile Foris Konrad Hoetzenecker Panja Maria Boehm Robab Breyer-Kohansal Katarina Zeder Gregor Gorkiewicz Francesca Polverino Slaven Crnkovic Grazyna Kwapiszewska Leigh Matthew Marsh |
| author_facet | Natalie Bordag Katharina Jandl Ayu Hutami Syarif Jürgen Gindlhuber Diana Schnoegl Ayse Ceren Mutgan Vasile Foris Konrad Hoetzenecker Panja Maria Boehm Robab Breyer-Kohansal Katarina Zeder Gregor Gorkiewicz Francesca Polverino Slaven Crnkovic Grazyna Kwapiszewska Leigh Matthew Marsh |
| author_sort | Natalie Bordag |
| collection | DOAJ |
| description | Summary: Chronic obstructive pulmonary disease (COPD) is a severe, progressive, and heterogeneous disease with a poor outcome. Inflammation plays a central role in disease pathogenesis; however, the interplay between immune changes and disease heterogeneity has been difficult to unravel. We performed a multilevel immunoinflammatory characterization of patients with COPD using flow cytometry, cytokine profiling, single-cell, or spatial transcriptomics in combination with machine learning algorithms. Our cross-cohort analysis demonstrated shared skewing of immune profiles in COPD lungs toward adaptive immune cells. We furthermore identified a subgroup of patients with COPD with a distinct immune profile, characterized by increased antigen-presenting cells, mast cells, and CD8+ cells, and circulating IL-1β, IFN-β, and GM-CSF, that were associated with increased emphysema severity and decreased gas exchange parameters independent of their GOLD-stage. Our findings suggest that unbiased immune profiling can refine disease classification and reveal inflammation-driven disease subtypes with potential relevance for prognosis and treatment strategies. |
| format | Article |
| id | doaj-art-696f50d59e834e749c044ac7bfdc6899 |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-696f50d59e834e749c044ac7bfdc68992025-08-20T03:33:38ZengElsevieriScience2589-00422025-07-0128711296610.1016/j.isci.2025.112966Machine learning assisted immune profiling of COPD identifies a unique emphysema subtype independent of GOLD stageNatalie Bordag0Katharina Jandl1Ayu Hutami Syarif2Jürgen Gindlhuber3Diana Schnoegl4Ayse Ceren Mutgan5Vasile Foris6Konrad Hoetzenecker7Panja Maria Boehm8Robab Breyer-Kohansal9Katarina Zeder10Gregor Gorkiewicz11Francesca Polverino12Slaven Crnkovic13Grazyna Kwapiszewska14Leigh Matthew Marsh15Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Styria 8010, Austria; Department of Dermatology and Venereology, Medical University of Graz, Graz, Styria 8010, AustriaLudwig Boltzmann Institute for Lung Vascular Research, Graz, Styria 8010, Austria; Division of Pharmacology, Otto Loewi Research Centre, Graz, Styria 8010, AustriaLudwig Boltzmann Institute for Lung Vascular Research, Graz, Styria 8010, Austria; Otto Loewi Research Centre, Lung Research Cluster, Medical University of Graz, Graz, Styria 8010, AustriaLudwig Boltzmann Institute for Lung Vascular Research, Graz, Styria 8010, Austria; Otto Loewi Research Centre, Lung Research Cluster, Medical University of Graz, Graz, Styria 8010, AustriaLudwig Boltzmann Institute for Lung Vascular Research, Graz, Styria 8010, AustriaLudwig Boltzmann Institute for Lung Vascular Research, Graz, Styria 8010, Austria; Otto Loewi Research Centre, Lung Research Cluster, Medical University of Graz, Graz, Styria 8010, AustriaLudwig Boltzmann Institute for Lung Vascular Research, Graz, Styria 8010, Austria; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA; Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, Graz, Styria 8010, AustriaDepartment of Thoracic Surgery, Medical University of Vienna, Vienna, Vienna 1090, AustriaLudwig Boltzmann Institute for Lung Vascular Research, Graz, Styria 8010, Austria; Department of Thoracic Surgery, Medical University of Vienna, Vienna, Vienna 1090, AustriaLudwig Boltzmann Institute for Lung Health, Vienna, Vienna 1140, Austria; Department of Respiratory and Pulmonary Diseases, Vienna Healthcare Group, Clinic Hietzing, Vienna, Vienna 1090, AustriaLudwig Boltzmann Institute for Lung Vascular Research, Graz, Styria 8010, Austria; Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, Graz, Styria 8010, Austria; University of Maryland, Institute of Health Computing, Bethesda, MD 20852, USADiagnostic and Research Institute of Pathology, Medical University of Graz, Graz, Styria 8010, AustriaBaylor College of Medicine, Department of Medicine, Houston, TX 77030, USALudwig Boltzmann Institute for Lung Vascular Research, Graz, Styria 8010, Austria; Otto Loewi Research Centre, Lung Research Cluster, Medical University of Graz, Graz, Styria 8010, Austria; Institute for Lung Health, Cardiopulmonary Institute, Member of the German Center for Lung Research, Justus-Liebig University Giessen, 35392 Giessen, GermanyLudwig Boltzmann Institute for Lung Vascular Research, Graz, Styria 8010, Austria; Otto Loewi Research Centre, Lung Research Cluster, Medical University of Graz, Graz, Styria 8010, Austria; Institute for Lung Health, Cardiopulmonary Institute, Member of the German Center for Lung Research, Justus-Liebig University Giessen, 35392 Giessen, GermanyLudwig Boltzmann Institute for Lung Vascular Research, Graz, Styria 8010, Austria; Otto Loewi Research Centre, Lung Research Cluster, Medical University of Graz, Graz, Styria 8010, Austria; Corresponding authorSummary: Chronic obstructive pulmonary disease (COPD) is a severe, progressive, and heterogeneous disease with a poor outcome. Inflammation plays a central role in disease pathogenesis; however, the interplay between immune changes and disease heterogeneity has been difficult to unravel. We performed a multilevel immunoinflammatory characterization of patients with COPD using flow cytometry, cytokine profiling, single-cell, or spatial transcriptomics in combination with machine learning algorithms. Our cross-cohort analysis demonstrated shared skewing of immune profiles in COPD lungs toward adaptive immune cells. We furthermore identified a subgroup of patients with COPD with a distinct immune profile, characterized by increased antigen-presenting cells, mast cells, and CD8+ cells, and circulating IL-1β, IFN-β, and GM-CSF, that were associated with increased emphysema severity and decreased gas exchange parameters independent of their GOLD-stage. Our findings suggest that unbiased immune profiling can refine disease classification and reveal inflammation-driven disease subtypes with potential relevance for prognosis and treatment strategies.http://www.sciencedirect.com/science/article/pii/S2589004225012271respiratory medicinemachine learning |
| spellingShingle | Natalie Bordag Katharina Jandl Ayu Hutami Syarif Jürgen Gindlhuber Diana Schnoegl Ayse Ceren Mutgan Vasile Foris Konrad Hoetzenecker Panja Maria Boehm Robab Breyer-Kohansal Katarina Zeder Gregor Gorkiewicz Francesca Polverino Slaven Crnkovic Grazyna Kwapiszewska Leigh Matthew Marsh Machine learning assisted immune profiling of COPD identifies a unique emphysema subtype independent of GOLD stage iScience respiratory medicine machine learning |
| title | Machine learning assisted immune profiling of COPD identifies a unique emphysema subtype independent of GOLD stage |
| title_full | Machine learning assisted immune profiling of COPD identifies a unique emphysema subtype independent of GOLD stage |
| title_fullStr | Machine learning assisted immune profiling of COPD identifies a unique emphysema subtype independent of GOLD stage |
| title_full_unstemmed | Machine learning assisted immune profiling of COPD identifies a unique emphysema subtype independent of GOLD stage |
| title_short | Machine learning assisted immune profiling of COPD identifies a unique emphysema subtype independent of GOLD stage |
| title_sort | machine learning assisted immune profiling of copd identifies a unique emphysema subtype independent of gold stage |
| topic | respiratory medicine machine learning |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225012271 |
| work_keys_str_mv | AT nataliebordag machinelearningassistedimmuneprofilingofcopdidentifiesauniqueemphysemasubtypeindependentofgoldstage AT katharinajandl machinelearningassistedimmuneprofilingofcopdidentifiesauniqueemphysemasubtypeindependentofgoldstage AT ayuhutamisyarif machinelearningassistedimmuneprofilingofcopdidentifiesauniqueemphysemasubtypeindependentofgoldstage AT jurgengindlhuber machinelearningassistedimmuneprofilingofcopdidentifiesauniqueemphysemasubtypeindependentofgoldstage AT dianaschnoegl machinelearningassistedimmuneprofilingofcopdidentifiesauniqueemphysemasubtypeindependentofgoldstage AT aysecerenmutgan machinelearningassistedimmuneprofilingofcopdidentifiesauniqueemphysemasubtypeindependentofgoldstage AT vasileforis machinelearningassistedimmuneprofilingofcopdidentifiesauniqueemphysemasubtypeindependentofgoldstage AT konradhoetzenecker machinelearningassistedimmuneprofilingofcopdidentifiesauniqueemphysemasubtypeindependentofgoldstage AT panjamariaboehm machinelearningassistedimmuneprofilingofcopdidentifiesauniqueemphysemasubtypeindependentofgoldstage AT robabbreyerkohansal machinelearningassistedimmuneprofilingofcopdidentifiesauniqueemphysemasubtypeindependentofgoldstage AT katarinazeder machinelearningassistedimmuneprofilingofcopdidentifiesauniqueemphysemasubtypeindependentofgoldstage AT gregorgorkiewicz machinelearningassistedimmuneprofilingofcopdidentifiesauniqueemphysemasubtypeindependentofgoldstage AT francescapolverino machinelearningassistedimmuneprofilingofcopdidentifiesauniqueemphysemasubtypeindependentofgoldstage AT slavencrnkovic machinelearningassistedimmuneprofilingofcopdidentifiesauniqueemphysemasubtypeindependentofgoldstage AT grazynakwapiszewska machinelearningassistedimmuneprofilingofcopdidentifiesauniqueemphysemasubtypeindependentofgoldstage AT leighmatthewmarsh machinelearningassistedimmuneprofilingofcopdidentifiesauniqueemphysemasubtypeindependentofgoldstage |