Blood-based Transcriptomic and Proteomic Biomarkers of Emphysema
Rationale: Emphysema is a chronic obstructive pulmonary disease phenotype with important prognostic implications. Identifying blood-based biomarkers of emphysema will facilitate early diagnosis and development of targeted therapies. Objectives: To discover blood omics biomarkers for chest computed tomography-quantified emphysema and develop predictive biomarker panels. Methods: Emphysema blood biomarker discovery was performed using differential gene expression, alternative splicing, and protein association analyses in a training sample of 2,370 COPDGene participants with available blood RNA sequencing, plasma proteomics, and clinical data. Internal validation was conducted in a COPDGene testing sample (n = 1,016), and external validation was done in the ECLIPSE study (n = 526). Because low body mass index (BMI) and emphysema often co-occur, we performed a mediation analysis to quantify the effect of BMI on gene and protein associations with emphysema. Elastic net models with bootstrapping were also developed in the training sample sequentially using clinical, blood cell proportions, RNA-sequencing, and proteomic biomarkers to predict quantitative emphysema. Model accuracy was assessed by the area under the receiver operating characteristic curves for subjects stratified into tertiles of emphysema severity. Measurements and Main Results: Totals of 3,829 genes, 942 isoforms, 260 exons, and 714 proteins were significantly associated with emphysema (false discovery rate, 5%) and yielded 11 biological pathways. Seventy-four percent of these genes and 62% of these proteins showed mediation by BMI. Our prediction models demonstrated reasonable predictive performance in both COPDGene and ECLIPSE. The highest-performing model used clinical, blood cell, and protein data (area under the receiver operating characteristic curve in COPDGene testing, 0.90; 95% confidence interval, 0.85-0.90). Conclusions: Blood transcriptome and proteome-wide analyses revealed key biological pathways of emphysema and enhanced the prediction of emphysema.
| Errataetall: |
CommentIn: Am J Respir Crit Care Med. 2024 Feb 1;209(3):235-237. - PMID 38078855 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:209 |
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| Enthalten in: |
American journal of respiratory and critical care medicine - 209(2024), 3 vom: 01. Feb., Seite 273-287 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Suryadevara, Rahul [VerfasserIn] |
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| Links: |
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| Themen: |
Biomarkers |
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| Anmerkungen: |
Date Completed 02.02.2024 Date Revised 07.02.2024 published: Print CommentIn: Am J Respir Crit Care Med. 2024 Feb 1;209(3):235-237. - PMID 38078855 Citation Status MEDLINE |
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| doi: |
10.1164/rccm.202301-0067OC |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM364097914 |
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| 100 | 1 | |a Suryadevara, Rahul |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Blood-based Transcriptomic and Proteomic Biomarkers of Emphysema |
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| 500 | |a CommentIn: Am J Respir Crit Care Med. 2024 Feb 1;209(3):235-237. - PMID 38078855 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Rationale: Emphysema is a chronic obstructive pulmonary disease phenotype with important prognostic implications. Identifying blood-based biomarkers of emphysema will facilitate early diagnosis and development of targeted therapies. Objectives: To discover blood omics biomarkers for chest computed tomography-quantified emphysema and develop predictive biomarker panels. Methods: Emphysema blood biomarker discovery was performed using differential gene expression, alternative splicing, and protein association analyses in a training sample of 2,370 COPDGene participants with available blood RNA sequencing, plasma proteomics, and clinical data. Internal validation was conducted in a COPDGene testing sample (n = 1,016), and external validation was done in the ECLIPSE study (n = 526). Because low body mass index (BMI) and emphysema often co-occur, we performed a mediation analysis to quantify the effect of BMI on gene and protein associations with emphysema. Elastic net models with bootstrapping were also developed in the training sample sequentially using clinical, blood cell proportions, RNA-sequencing, and proteomic biomarkers to predict quantitative emphysema. Model accuracy was assessed by the area under the receiver operating characteristic curves for subjects stratified into tertiles of emphysema severity. Measurements and Main Results: Totals of 3,829 genes, 942 isoforms, 260 exons, and 714 proteins were significantly associated with emphysema (false discovery rate, 5%) and yielded 11 biological pathways. Seventy-four percent of these genes and 62% of these proteins showed mediation by BMI. Our prediction models demonstrated reasonable predictive performance in both COPDGene and ECLIPSE. The highest-performing model used clinical, blood cell, and protein data (area under the receiver operating characteristic curve in COPDGene testing, 0.90; 95% confidence interval, 0.85-0.90). Conclusions: Blood transcriptome and proteome-wide analyses revealed key biological pathways of emphysema and enhanced the prediction of emphysema | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a biomarkers | |
| 650 | 4 | |a emphysema | |
| 650 | 4 | |a prediction | |
| 650 | 4 | |a proteomics | |
| 650 | 4 | |a transcriptomics | |
| 650 | 7 | |a Biomarkers |2 NLM | |
| 700 | 1 | |a Gregory, Andrew |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Robin |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Zhonghui |e verfasserin |4 aut | |
| 700 | 1 | |a Masoomi, Aria |e verfasserin |4 aut | |
| 700 | 1 | |a Lutz, Sharon M |e verfasserin |4 aut | |
| 700 | 1 | |a Berman, Seth |e verfasserin |4 aut | |
| 700 | 1 | |a Yun, Jeong H |e verfasserin |4 aut | |
| 700 | 1 | |a Saferali, Aabida |e verfasserin |4 aut | |
| 700 | 1 | |a Ryu, Min Hyung |e verfasserin |4 aut | |
| 700 | 1 | |a Moll, Matthew |e verfasserin |4 aut | |
| 700 | 1 | |a Sin, Don D |e verfasserin |4 aut | |
| 700 | 1 | |a Hersh, Craig P |e verfasserin |4 aut | |
| 700 | 1 | |a Silverman, Edwin K |e verfasserin |4 aut | |
| 700 | 1 | |a Dy, Jennifer |e verfasserin |4 aut | |
| 700 | 1 | |a Pratte, Katherine A |e verfasserin |4 aut | |
| 700 | 1 | |a Bowler, Russell P |e verfasserin |4 aut | |
| 700 | 1 | |a Castaldi, Peter J |e verfasserin |4 aut | |
| 700 | 1 | |a Boueiz, Adel |e verfasserin |4 aut | |
| 700 | 0 | |a COPDGene investigators |e verfasserin |4 aut | |
| 700 | 1 | |a Crapo, James D |e investigator |4 oth | |
| 700 | 1 | |a Silverman, Edwin K |e investigator |4 oth | |
| 700 | 1 | |a Make, Barry J |e investigator |4 oth | |
| 700 | 1 | |a Regan, Elizabeth A |e investigator |4 oth | |
| 700 | 1 | |a Beaty, Terri H |e investigator |4 oth | |
| 700 | 1 | |a Castaldi, Peter J |e investigator |4 oth | |
| 700 | 1 | |a Cho, Michael H |e investigator |4 oth | |
| 700 | 1 | |a DeMeo, Dawn L |e investigator |4 oth | |
| 700 | 1 | |a Boueiz, Adel |e investigator |4 oth | |
| 700 | 1 | |a Foreman, Marilyn G |e investigator |4 oth | |
| 700 | 1 | |a Ghosh, Auyon |e investigator |4 oth | |
| 700 | 1 | |a Hayden, Lystra P |e investigator |4 oth | |
| 700 | 1 | |a Hersh, Craig P |e investigator |4 oth | |
| 700 | 1 | |a Hetmanski, Jacqueline |e investigator |4 oth | |
| 700 | 1 | |a Hobbs, Brian D |e investigator |4 oth | |
| 700 | 1 | |a Hokanson, John E |e investigator |4 oth | |
| 700 | 1 | |a Kim, Wonji |e investigator |4 oth | |
| 700 | 1 | |a Laird, Nan |e investigator |4 oth | |
| 700 | 1 | |a Lange, Christoph |e investigator |4 oth | |
| 700 | 1 | |a Lutz, Sharon M |e investigator |4 oth | |
| 700 | 1 | |a McDonald, Merry-Lynn |e investigator |4 oth | |
| 700 | 1 | |a Prokopenko, Dmitry |e investigator |4 oth | |
| 700 | 1 | |a Moll, Matthew |e investigator |4 oth | |
| 700 | 1 | |a Morrow, Jarrett |e investigator |4 oth | |
| 700 | 1 | |a Qiao, Dandi |e investigator |4 oth | |
| 700 | 1 | |a Regan, Elizabeth A |e investigator |4 oth | |
| 700 | 1 | |a Saferali, Aabida |e investigator |4 oth | |
| 700 | 1 | |a Sakornsakolpat, Phuwanat |e investigator |4 oth | |
| 700 | 1 | |a Silverman, Edwin K |e investigator |4 oth | |
| 700 | 1 | |a Wan, Emily S |e investigator |4 oth | |
| 700 | 1 | |a Yun, Jeong |e investigator |4 oth | |
| 700 | 1 | |a Centeno, Juan Pablo |e investigator |4 oth | |
| 700 | 1 | |a Charbonnier, Jean-Paul |e investigator |4 oth | |
| 700 | 1 | |a Coxson, Harvey O |e investigator |4 oth | |
| 700 | 1 | |a Galban, Craig J |e investigator |4 oth | |
| 700 | 1 | |a Han, MeiLan K |e investigator |4 oth | |
| 700 | 1 | |a Hoffman, Eric A |e investigator |4 oth | |
| 700 | 1 | |a Humphries, Stephen |e investigator |4 oth | |
| 700 | 1 | |a Jacobson, Francine L |e investigator |4 oth | |
| 700 | 1 | |a Judy, Philip F |e investigator |4 oth | |
| 700 | 1 | |a Kazerooni, Ella A |e investigator |4 oth | |
| 700 | 1 | |a Kluiber, Alex |e investigator |4 oth | |
| 700 | 1 | |a Lynch, David A |e investigator |4 oth | |
| 700 | 1 | |a Nardelli, Pietro |e investigator |4 oth | |
| 700 | 1 | |a Newell, John D |c Jr |e investigator |4 oth | |
| 700 | 1 | |a Notary, Aleena |e investigator |4 oth | |
| 700 | 1 | |a Oh, Andrea |e investigator |4 oth | |
| 700 | 1 | |a Regan, Elizabeth A |e investigator |4 oth | |
| 700 | 1 | |a Ross, James C |e investigator |4 oth | |
| 700 | 1 | |a Estepar, Raul San Jose |e investigator |4 oth | |
| 700 | 1 | |a Schroeder, Joyce |e investigator |4 oth | |
| 700 | 1 | |a Sieren, Jered |e investigator |4 oth | |
| 700 | 1 | |a Stoel, Berend C |e investigator |4 oth | |
| 700 | 1 | |a Tschirren, Juerg |e investigator |4 oth | |
| 700 | 1 | |a Van Beek, Edwin |e investigator |4 oth | |
| 700 | 1 | |a van Ginneken, Bram |e investigator |4 oth | |
| 700 | 1 | |a van Rikxoort, Eva |e investigator |4 oth | |
| 700 | 1 | |a Sanchez Ferrero, Gonzalo Vegas |e investigator |4 oth | |
| 700 | 1 | |a Veitel, Lucas |e investigator |4 oth | |
| 700 | 1 | |a Washko, George R |e investigator |4 oth | |
| 700 | 1 | |a Wilson, Carla G |e investigator |4 oth | |
| 700 | 1 | |a Jensen, Robert |e investigator |4 oth | |
| 700 | 1 | |a Everett, Douglas |e investigator |4 oth | |
| 700 | 1 | |a Crooks, Jim |e investigator |4 oth | |
| 700 | 1 | |a Pratte, Katherine |e investigator |4 oth | |
| 700 | 1 | |a Strand, Matt |e investigator |4 oth | |
| 700 | 1 | |a Wilson, Carla G |e investigator |4 oth | |
| 700 | 1 | |a Hokanson, John E |e investigator |4 oth | |
| 700 | 1 | |a Austin, Erin |e investigator |4 oth | |
| 700 | 1 | |a Kinney, Gregory |e investigator |4 oth | |
| 700 | 1 | |a Lutz, Sharon M |e investigator |4 oth | |
| 700 | 1 | |a Young, Kendra A |e investigator |4 oth | |
| 700 | 1 | |a Bhatt, Surya P |e investigator |4 oth | |
| 700 | 1 | |a Bon, Jessica |e investigator |4 oth | |
| 700 | 1 | |a Diaz, Alejandro A |e investigator |4 oth | |
| 700 | 1 | |a Han, MeiLan K |e investigator |4 oth | |
| 700 | 1 | |a Make, Barry |e investigator |4 oth | |
| 700 | 1 | |a Murray, Susan |e investigator |4 oth | |
| 700 | 1 | |a Regan, Elizabeth |e investigator |4 oth | |
| 700 | 1 | |a Soler, Xavier |e investigator |4 oth | |
| 700 | 1 | |a Wilson, Carla G |e investigator |4 oth | |
| 700 | 1 | |a Bowler, Russell P |e investigator |4 oth | |
| 700 | 1 | |a Kechris, Katerina |e investigator |4 oth | |
| 700 | 1 | |a Kashani, Farnoush Banaei |e investigator |4 oth | |
| 700 | 1 | |a Curtis, Jeffrey L |e investigator |4 oth | |
| 700 | 1 | |a Pernicano, Perry G |e investigator |4 oth | |
| 700 | 1 | |a Hanania, Nicola |e investigator |4 oth | |
| 700 | 1 | |a Atik, Mustafa |e investigator |4 oth | |
| 700 | 1 | |a Boriek, Aladin |e investigator |4 oth | |
| 700 | 1 | |a Guntupalli, Kalpatha |e investigator |4 oth | |
| 700 | 1 | |a Guy, Elizabeth |e investigator |4 oth | |
| 700 | 1 | |a Parulekar, Amit |e investigator |4 oth | |
| 700 | 1 | |a DeMeo, Dawn L |e investigator |4 oth | |
| 700 | 1 | |a Hersh, Craig |e investigator |4 oth | |
| 700 | 1 | |a Jacobson, Francine L |e investigator |4 oth | |
| 700 | 1 | |a Washko, George |e investigator |4 oth | |
| 700 | 1 | |a Graham Barr, R |e investigator |4 oth | |
| 700 | 1 | |a Austin, John |e investigator |4 oth | |
| 700 | 1 | |a D'Souza, Belinda |e investigator |4 oth | |
| 700 | 1 | |a Thomashow, Byron |e investigator |4 oth | |
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