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Distinct COPD subty...
Distinct COPD subtypes in former smokers revealed by gene network perturbation analysis
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- Buschur, Kristina L. (author)
- Univ Pittsburgh, Dept Computat & Syst Biol, Sch Med, Pittsburgh, PA 15260 USA.;Joint CMU Pitt PhD Program Computat Biol, Pittsburgh, PA 15213 USA.;Columbia Univ, Div Gen Med, Med Ctr, New York, NY USA.;New York Genome Ctr, New York, NY USA.
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- Riley, Craig (author)
- Univ Pittsburgh, Dept Med, Div Pulm Med, Pittsburgh, PA USA.
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- Saferali, Aabida (author)
- Brigham & Womens Hosp, Channing Div Network Med, Boston, MA USA.
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- Castaldi, Peter (author)
- Brigham & Womens Hosp, Channing Div Network Med, Boston, MA USA.
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- Zhang, Grace (author)
- Univ Pittsburgh, Dept Computat & Syst Biol, Sch Med, Pittsburgh, PA 15260 USA.
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- Aguet, Francois (author)
- Broad Inst MIT & Harvard, Cambridge, MA USA.
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- Ardlie, Kristin G. (author)
- Broad Inst MIT & Harvard, Cambridge, MA USA.
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- Durda, Peter (author)
- Univ Vermont, Larner Coll Med, Dept Pathol & Lab Med, Burlington, VT USA.
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- Craig Johnson, W. (author)
- Univ Washington, Dept Biostat, Seattle, WA USA.
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- Kasela, Silva (author)
- New York Genome Ctr, New York, NY USA.;Columbia Univ, Dept Syst Biol, New York, NY USA.
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- Liu, Yongmei (author)
- Duke Univ, Duke Mol Physiol Inst, Dept Med,Med Ctr, Div Cardiol, Durham, NC USA.
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- Manichaikul, Ani (author)
- Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA.
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- Rich, Stephen S. (author)
- Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA.
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- Rotter, Jerome I. (author)
- UCLA Med Ctr, Inst Translat Genom & Populat Sci, Lundquist Inst Biomed Innovat Harbor, Dept Pediat, Torrance, CA USA.
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- Smith, Josh (author)
- Univ Washington, Northwest Genome Ctr, Seattle, WA USA.
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- Taylor, Kent D. (author)
- UCLA Med Ctr, Inst Translat Genom & Populat Sci, Lundquist Inst Biomed Innovat Harbor, Dept Pediat, Torrance, CA USA.
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- Tracy, Russell P. (author)
- Univ Vermont, Larner Coll Med, Dept Pathol & Lab Med, Burlington, VT USA.;Univ Vermont, Larner Coll Med, Dept Biochem, Burlington, VT USA.
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- Lappalainen, Tuuli (author)
- KTH,Genteknologi,Science for Life Laboratory, SciLifeLab,New York Genome Ctr, New York, NY USA.;Columbia Univ, Dept Syst Biol, New York, NY USA
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- Graham Barr, R. (author)
- Columbia Univ, Div Gen Med, Med Ctr, New York, NY USA.
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- Sciurba, Frank (author)
- Univ Pittsburgh, Dept Med, Div Pulm Med, Pittsburgh, PA USA.
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- Hersh, Craig P. (author)
- Brigham & Womens Hosp, Channing Div Network Med, Boston, MA USA.
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- Benos, Panayiotis V. (author)
- Univ Pittsburgh, Dept Computat & Syst Biol, Sch Med, Pittsburgh, PA 15260 USA.;Joint CMU Pitt PhD Program Computat Biol, Pittsburgh, PA 15213 USA.;Univ Florida, Dept Epidemiol, 2004 Mowry Rd, Gainesville, FL 32603 USA.
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Univ Pittsburgh, Dept Computat & Syst Biol, Sch Med, Pittsburgh, PA 15260 USA;Joint CMU Pitt PhD Program Computat Biol, Pittsburgh, PA 15213 USA.;Columbia Univ, Div Gen Med, Med Ctr, New York, NY USA.;New York Genome Ctr, New York, NY USA. Univ Pittsburgh, Dept Med, Div Pulm Med, Pittsburgh, PA USA. (creator_code:org_t)
- 2023-01-25
- 2023
- English.
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In: Respiratory Research. - : Springer Nature. - 1465-9921 .- 1465-993X. ; 24:1
- Related links:
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https://doi.org/10.1...
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Abstract
Subject headings
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- BackgroundChronic obstructive pulmonary disease (COPD) varies significantly in symptomatic and physiologic presentation. Identifying disease subtypes from molecular data, collected from easily accessible blood samples, can help stratify patients and guide disease management and treatment.MethodsBlood gene expression measured by RNA-sequencing in the COPDGene Study was analyzed using a network perturbation analysis method. Each COPD sample was compared against a learned reference gene network to determine the part that is deregulated. Gene deregulation values were used to cluster the disease samples.ResultsThe discovery set included 617 former smokers from COPDGene. Four distinct gene network subtypes are identified with significant differences in symptoms, exercise capacity and mortality. These clusters do not necessarily correspond with the levels of lung function impairment and are independently validated in two external cohorts: 769 former smokers from COPDGene and 431 former smokers in the Multi-Ethnic Study of Atherosclerosis (MESA). Additionally, we identify several genes that are significantly deregulated across these subtypes, including DSP and GSTM1, which have been previously associated with COPD through genome-wide association study (GWAS).ConclusionsThe identified subtypes differ in mortality and in their clinical and functional characteristics, underlining the need for multi-dimensional assessment potentially supplemented by selected markers of gene expression. The subtypes were consistent across cohorts and could be used for new patient stratification and disease prognosis.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Lungmedicin och allergi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Respiratory Medicine and Allergy (hsv//eng)
Keyword
- COPD
- Graphical models
- Gene expression
- Disease subtypes
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Buschur, Kristin ...
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Riley, Craig
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Saferali, Aabida
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Castaldi, Peter
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Zhang, Grace
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Aguet, Francois
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show more...
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Ardlie, Kristin ...
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Durda, Peter
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Craig Johnson, W ...
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Kasela, Silva
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Liu, Yongmei
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Manichaikul, Ani
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Rich, Stephen S.
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Rotter, Jerome I ...
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Smith, Josh
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Taylor, Kent D.
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Tracy, Russell P ...
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Lappalainen, Tuu ...
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Graham Barr, R.
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Sciurba, Frank
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Hersh, Craig P.
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Benos, Panayioti ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Respiratory Medi ...
- Articles in the publication
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Respiratory Rese ...
- By the university
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Royal Institute of Technology