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Distinct Platelet Ribonucleic Acid Signatures in Patients with Pulmonary Hypertension. / Smits, A Josien; Arkani, Mohammad; In 't Veld, Sjors G J G et al.

In: Annals of the American Thoracic Society, Vol. 19, No. 10, 01.10.2022, p. 1650-1660.

Research output: Contribution to journalArticleAcademicpeer-review

Harvard

Smits, AJ, Arkani, M, In 't Veld, SGJG, Huis In 't Veld, AE, Sol, N, Groeneveldt, JA, Botros, L, Braams, NJ, Jansen, SM, Ramaker, J, Zwaan, K, Post, E, Nossent, EJ, Boonstra, A, de Man, FS, Vonk Noordegraaf, A, Gomez-Arroyo, J, Best, MG, Wurdinger, T & Bogaard, HJ 2022, 'Distinct Platelet Ribonucleic Acid Signatures in Patients with Pulmonary Hypertension', Annals of the American Thoracic Society, vol. 19, no. 10, pp. 1650-1660. https://doi.org/10.1513/AnnalsATS.202201-085OC

APA

Smits, A. J., Arkani, M., In 't Veld, S. G. J. G., Huis In 't Veld, A. E., Sol, N., Groeneveldt, J. A., Botros, L., Braams, N. J., Jansen, S. M., Ramaker, J., Zwaan, K., Post, E., Nossent, E. J., Boonstra, A., de Man, F. S., Vonk Noordegraaf, A., Gomez-Arroyo, J., Best, M. G., Wurdinger, T., & Bogaard, H. J. (2022). Distinct Platelet Ribonucleic Acid Signatures in Patients with Pulmonary Hypertension. Annals of the American Thoracic Society, 19(10), 1650-1660. https://doi.org/10.1513/AnnalsATS.202201-085OC

Vancouver

Smits AJ, Arkani M, In 't Veld SGJG, Huis In 't Veld AE, Sol N, Groeneveldt JA et al. Distinct Platelet Ribonucleic Acid Signatures in Patients with Pulmonary Hypertension. Annals of the American Thoracic Society. 2022 Oct 1;19(10):1650-1660. Epub 2022 May 10. doi: 10.1513/AnnalsATS.202201-085OC

Author

Smits, A Josien ; Arkani, Mohammad ; In 't Veld, Sjors G J G et al. / Distinct Platelet Ribonucleic Acid Signatures in Patients with Pulmonary Hypertension. In: Annals of the American Thoracic Society. 2022 ; Vol. 19, No. 10. pp. 1650-1660.

BibTeX

@article{b8f0c52862ea41b19e7951e2f6b6299b,
title = "Distinct Platelet Ribonucleic Acid Signatures in Patients with Pulmonary Hypertension",
abstract = "Rationale: Pulmonary hypertension encompasses progressive disorders leading to right ventricular dysfunction and early death. Late detection is an important cause of poor clinical outcomes. However, biomarkers that accurately predict the presence of pulmonary hypertension are currently lacking. Objectives: In this study, we provide evidence that blood platelets contain a distinctive ribonucleic acid (RNA) profile that may be exploited for the detection of pulmonary hypertension. Methods: Blood platelet RNA was isolated prospectively from 177 prevalent patients with different subtypes of pulmonary hypertension as well as 195 control subjects clinically not suspected of pulmonary hypertension. Sequencing libraries were created using SMARTer (Switching Mechanism at 5' end of RNA Template) copy desoxyribonucleic acid amplification and sequenced on the Illumina High Throughput Sequencing platform. RNA-sequencing reads were mapped to the human reference genome, and intron-spanning spliced RNA reads were selected. Differential spliced RNA panels were calculated by analysis of variance statistics. A particle swarm optimization-enhanced classification algorithm was built employing a development (n = 213 samples) and independent validation series (n = 159 samples). Results: We detected a total of 4,014 different RNAs in blood platelets from patients with pulmonary hypertension (n = 177) and asymptomatic control subjects (n = 195). Gene ontology analysis revealed enhanced RNA concentrations for genes related to RNA processing, translation, and mitochondrial function. A particle swarm optimization-selected RNA panel of 408 distinctive differentially spliced RNAs mediated detection of pulmonary hypertension with 93% sensitivity, 62% specificity, 77% accuracy, 0.89 (95% confidence interval, 0.83-0.93) area under the curve, and a negative predictive value of 91% in the independent validation series. The prediction score was independent of age, sex, smoking, pulmonary hypertension subtype, and the use of pulmonary hypertension-specific medication or anticoagulants. Conclusions: A platelet RNA panel may accurately discriminate patients with pulmonary hypertension from asymptomatic control subjects. In the light of current diagnostic delays, this study is the starting point for further development and evaluation of a platelet RNA-based blood test to ultimately improve early diagnosis and clinical outcomes in patients with pulmonary hypertension.",
keywords = "biomarkers, blood platelets, hypertension, pulmonary",
author = "Smits, {A Josien} and Mohammad Arkani and {In 't Veld}, {Sjors G J G} and {Huis In 't Veld}, {Anna E} and Nik Sol and Groeneveldt, {Joanne A} and Liza Botros and Braams, {Natalia J} and Jansen, {Samara Ma} and Jip Ramaker and Kenn Zwaan and Edward Post and Nossent, {Esther J} and Anco Boonstra and {de Man}, {Frances S} and {Vonk Noordegraaf}, Anton and Jose Gomez-Arroyo and Best, {Myron G} and Tom Wurdinger and Bogaard, {Harm Jan}",
year = "2022",
month = oct,
day = "1",
doi = "10.1513/AnnalsATS.202201-085OC",
language = "English",
volume = "19",
pages = "1650--1660",
journal = "Annals of the American Thoracic Society",
issn = "2325-6621",
publisher = "American Thoracic Society",
number = "10",

}

RIS

TY - JOUR

T1 - Distinct Platelet Ribonucleic Acid Signatures in Patients with Pulmonary Hypertension

AU - Smits, A Josien

AU - Arkani, Mohammad

AU - In 't Veld, Sjors G J G

AU - Huis In 't Veld, Anna E

AU - Sol, Nik

AU - Groeneveldt, Joanne A

AU - Botros, Liza

AU - Braams, Natalia J

AU - Jansen, Samara Ma

AU - Ramaker, Jip

AU - Zwaan, Kenn

AU - Post, Edward

AU - Nossent, Esther J

AU - Boonstra, Anco

AU - de Man, Frances S

AU - Vonk Noordegraaf, Anton

AU - Gomez-Arroyo, Jose

AU - Best, Myron G

AU - Wurdinger, Tom

AU - Bogaard, Harm Jan

PY - 2022/10/1

Y1 - 2022/10/1

N2 - Rationale: Pulmonary hypertension encompasses progressive disorders leading to right ventricular dysfunction and early death. Late detection is an important cause of poor clinical outcomes. However, biomarkers that accurately predict the presence of pulmonary hypertension are currently lacking. Objectives: In this study, we provide evidence that blood platelets contain a distinctive ribonucleic acid (RNA) profile that may be exploited for the detection of pulmonary hypertension. Methods: Blood platelet RNA was isolated prospectively from 177 prevalent patients with different subtypes of pulmonary hypertension as well as 195 control subjects clinically not suspected of pulmonary hypertension. Sequencing libraries were created using SMARTer (Switching Mechanism at 5' end of RNA Template) copy desoxyribonucleic acid amplification and sequenced on the Illumina High Throughput Sequencing platform. RNA-sequencing reads were mapped to the human reference genome, and intron-spanning spliced RNA reads were selected. Differential spliced RNA panels were calculated by analysis of variance statistics. A particle swarm optimization-enhanced classification algorithm was built employing a development (n = 213 samples) and independent validation series (n = 159 samples). Results: We detected a total of 4,014 different RNAs in blood platelets from patients with pulmonary hypertension (n = 177) and asymptomatic control subjects (n = 195). Gene ontology analysis revealed enhanced RNA concentrations for genes related to RNA processing, translation, and mitochondrial function. A particle swarm optimization-selected RNA panel of 408 distinctive differentially spliced RNAs mediated detection of pulmonary hypertension with 93% sensitivity, 62% specificity, 77% accuracy, 0.89 (95% confidence interval, 0.83-0.93) area under the curve, and a negative predictive value of 91% in the independent validation series. The prediction score was independent of age, sex, smoking, pulmonary hypertension subtype, and the use of pulmonary hypertension-specific medication or anticoagulants. Conclusions: A platelet RNA panel may accurately discriminate patients with pulmonary hypertension from asymptomatic control subjects. In the light of current diagnostic delays, this study is the starting point for further development and evaluation of a platelet RNA-based blood test to ultimately improve early diagnosis and clinical outcomes in patients with pulmonary hypertension.

AB - Rationale: Pulmonary hypertension encompasses progressive disorders leading to right ventricular dysfunction and early death. Late detection is an important cause of poor clinical outcomes. However, biomarkers that accurately predict the presence of pulmonary hypertension are currently lacking. Objectives: In this study, we provide evidence that blood platelets contain a distinctive ribonucleic acid (RNA) profile that may be exploited for the detection of pulmonary hypertension. Methods: Blood platelet RNA was isolated prospectively from 177 prevalent patients with different subtypes of pulmonary hypertension as well as 195 control subjects clinically not suspected of pulmonary hypertension. Sequencing libraries were created using SMARTer (Switching Mechanism at 5' end of RNA Template) copy desoxyribonucleic acid amplification and sequenced on the Illumina High Throughput Sequencing platform. RNA-sequencing reads were mapped to the human reference genome, and intron-spanning spliced RNA reads were selected. Differential spliced RNA panels were calculated by analysis of variance statistics. A particle swarm optimization-enhanced classification algorithm was built employing a development (n = 213 samples) and independent validation series (n = 159 samples). Results: We detected a total of 4,014 different RNAs in blood platelets from patients with pulmonary hypertension (n = 177) and asymptomatic control subjects (n = 195). Gene ontology analysis revealed enhanced RNA concentrations for genes related to RNA processing, translation, and mitochondrial function. A particle swarm optimization-selected RNA panel of 408 distinctive differentially spliced RNAs mediated detection of pulmonary hypertension with 93% sensitivity, 62% specificity, 77% accuracy, 0.89 (95% confidence interval, 0.83-0.93) area under the curve, and a negative predictive value of 91% in the independent validation series. The prediction score was independent of age, sex, smoking, pulmonary hypertension subtype, and the use of pulmonary hypertension-specific medication or anticoagulants. Conclusions: A platelet RNA panel may accurately discriminate patients with pulmonary hypertension from asymptomatic control subjects. In the light of current diagnostic delays, this study is the starting point for further development and evaluation of a platelet RNA-based blood test to ultimately improve early diagnosis and clinical outcomes in patients with pulmonary hypertension.

KW - biomarkers

KW - blood platelets

KW - hypertension

KW - pulmonary

UR - http://www.scopus.com/inward/record.url?scp=85137383280&partnerID=8YFLogxK

U2 - 10.1513/AnnalsATS.202201-085OC

DO - 10.1513/AnnalsATS.202201-085OC

M3 - Article

C2 - 35537078

VL - 19

SP - 1650

EP - 1660

JO - Annals of the American Thoracic Society

JF - Annals of the American Thoracic Society

SN - 2325-6621

IS - 10

ER -

ID: 24792151