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A Whole Blood Molecular Signature for Acute Myocardial Infarction

Evan D Muse, Eric R Kramer, Haiying Wang, Paddy Barrett, Fereshteh Parviz, Mark A Novotny, Roger S Lasken, Timothy A Jatkoe, Glenn Oliveira, Hongfan Peng, Jerry Lu, Marc C Connelly, Kurt Schilling, Chandra Rao, Ali Torkamani, Eric J. Topol
doi: https://doi.org/10.1101/045013
Evan D Muse
1The Scripps Translational Science Institute, The Scripps Research Institute, Scripps Health, La Jolla, USA
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Eric R Kramer
1The Scripps Translational Science Institute, The Scripps Research Institute, Scripps Health, La Jolla, USA
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Haiying Wang
2Ortho Clinical Diagnostics, Raritin, NJ, USA
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Paddy Barrett
1The Scripps Translational Science Institute, The Scripps Research Institute, Scripps Health, La Jolla, USA
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Fereshteh Parviz
3Janssen Research & Development, LLC, Huntingdon Valley, PA, USA
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Mark A Novotny
4J. Craig Venter Institute, La Jolla, CA, USA
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Roger S Lasken
4J. Craig Venter Institute, La Jolla, CA, USA
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Timothy A Jatkoe
2Ortho Clinical Diagnostics, Raritin, NJ, USA
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Glenn Oliveira
1The Scripps Translational Science Institute, The Scripps Research Institute, Scripps Health, La Jolla, USA
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Hongfan Peng
1The Scripps Translational Science Institute, The Scripps Research Institute, Scripps Health, La Jolla, USA
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Jerry Lu
5Biological Dynamics, San Diego, CA, USA
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Marc C Connelly
3Janssen Research & Development, LLC, Huntingdon Valley, PA, USA
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Kurt Schilling
6Ortho Clinical Diagnostics, Rochester, NY, USA
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Chandra Rao
3Janssen Research & Development, LLC, Huntingdon Valley, PA, USA
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Ali Torkamani
1The Scripps Translational Science Institute, The Scripps Research Institute, Scripps Health, La Jolla, USA
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Eric J. Topol
1The Scripps Translational Science Institute, The Scripps Research Institute, Scripps Health, La Jolla, USA
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  • For correspondence: etopol@scripps.edu
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ABSTRACT

Chest pain is a leading reason patients seek medical evaluation. While assays to detect myocyte death are used to diagnose a heart attack (acute myocardial infarction, AMI), there is no biomarker to indicate an impending cardiac event. Transcriptional patterns present in circulating endothelial cells (CEC) may provide a window into the plaque rupture process and identify a proximal biomarker for AMI. Thus, we aimed to identify a transcriptomic signature of AMI present in whole blood, but derived from CECs. Candidate genes indicative of AMI were nominated from microarray of enriched CEC samples, and then verified for detectability and predictive potential via qPCR in whole blood. This signature was validated in an independent cohort. Our findings suggest that a whole blood CEC-derived molecular signature identifies patients with AMI and sets the framework to potentially identify the earlier stages of an impending cardiac event where conventional biomarkers indicative of myonecrosis remain undetected.

AMI
acute myocardial infarction
AUC
area under the curve
CAD
coronary artery disease
CEC
circulating endothelial cells
CMP
circulating microparticles
CVD
cardiovascular disease
GSEA
gene set enrichment analysis
qPCR
quantitative polymerase chain reaction
ROC
receiver operator characteristic
Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted March 21, 2016.
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A Whole Blood Molecular Signature for Acute Myocardial Infarction
Evan D Muse, Eric R Kramer, Haiying Wang, Paddy Barrett, Fereshteh Parviz, Mark A Novotny, Roger S Lasken, Timothy A Jatkoe, Glenn Oliveira, Hongfan Peng, Jerry Lu, Marc C Connelly, Kurt Schilling, Chandra Rao, Ali Torkamani, Eric J. Topol
bioRxiv 045013; doi: https://doi.org/10.1101/045013
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A Whole Blood Molecular Signature for Acute Myocardial Infarction
Evan D Muse, Eric R Kramer, Haiying Wang, Paddy Barrett, Fereshteh Parviz, Mark A Novotny, Roger S Lasken, Timothy A Jatkoe, Glenn Oliveira, Hongfan Peng, Jerry Lu, Marc C Connelly, Kurt Schilling, Chandra Rao, Ali Torkamani, Eric J. Topol
bioRxiv 045013; doi: https://doi.org/10.1101/045013

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