Bayesian network analysis of panomic biological big data identifies the importance of triglyceride-rich LDL in atherosclerosis development

Szilard Voros; Aruna T. Bansal; Michael R. Barnes; Jagat Narula; Pal Maurovich-Horvat; Gustavo Vazquez; Idean B. Marvasty; Bradley O. Brown; Isaac D. Voros; William Harris; Viktor Voros; Thomas Dayspring; David Neff; Alex Greenfield; Leon Furchtgott; Bruce Church; Karl Runge; Iya Khalil; Boris Hayete; Diego Lucero; Alan T. Remaley; Roger S. Newton

doi:10.3389/fcvm.2022.960419

Bayesian network analysis of panomic biological big data identifies the importance of triglyceride-rich LDL in atherosclerosis development

Szilard Voros
, Aruna T. Bansal
, Michael R. Barnes
, Jagat Narula
, Pal Maurovich-Horvat
, Gustavo Vazquez
, Idean B. Marvasty
, Bradley O. Brown
, Isaac D. Voros
, William Harris
, Viktor Voros
, Thomas Dayspring
, David Neff
, Alex Greenfield
, Leon Furchtgott
, Bruce Church
, Karl Runge
, Iya Khalil
, Boris Hayete
, Diego Lucero

Alan T. Remaley, Roger S. Newton

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

Abstract

Introduction: We sought to explore biomarkers of coronary atherosclerosis in an unbiased fashion. Methods: We analyzed 665 patients (mean ± SD age, 56 ± 11 years; 47% male) from the GLOBAL clinical study (NCT01738828). Cases were defined by the presence of any discernable atherosclerotic plaque based on comprehensive cardiac computed tomography (CT). De novo Bayesian networks built out of 37,000 molecular measurements and 99 conventional biomarkers per patient examined the potential causality of specific biomarkers. Results: Most highly ranked biomarkers by gradient boosting were interleukin-6, symmetric dimethylarginine, LDL-triglycerides [LDL-TG], apolipoprotein B48, palmitoleic acid, small dense LDL, alkaline phosphatase, and asymmetric dimethylarginine. In Bayesian analysis, LDL-TG was directly linked to atherosclerosis in over 95% of the ensembles. Genetic variants in the genomic region encoding hepatic lipase (LIPC) were associated with LIPC gene expression, LDL-TG levels and with atherosclerosis. Discussion: Triglyceride-rich LDL particles, which can now be routinely measured with a direct homogenous assay, may play an important role in atherosclerosis development. Clinical trial registration: GLOBAL clinical study (Genetic Loci and the Burden of Atherosclerotic Lesions); [https://clinicaltrials.gov/ct2/show/NCT01738828?term=NCT01738828&rank=1], identifier [NCT01738828].

Original language	English
Article number	960419
Journal	Frontiers in Cardiovascular Medicine
Volume	9
DOIs	https://doi.org/10.3389/fcvm.2022.960419
State	Published - Jan 4 2023

Bibliographical note

Publisher Copyright:
Copyright © 2023 Voros, Bansal, Barnes, Narula, Maurovich-Horvat, Vazquez, Marvasty, Brown, Voros, Harris, Voros, Dayspring, Neff, Greenfield, Furchtgott, Church, Runge, Khalil, Hayete, Lucero, Remaley and Newton.

Funding

Global Genomics Group sponsored and funded the study and has filed patents on biomarker diagnosis of coronary artery disease. Denka Seiken provided financial support for manuscript preparation. Research by DL and AR was supported by intramural DIR funds from the National Heart, Lung and Blood Institute, NIH, Bethesda, MD.

Funders
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)

Keywords

Bayesian network analysis
LDL-triglycerides
cardiovascular risk
hepatic lipase
omics
triglyceride-rich LDL

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

Access to Document

10.3389/fcvm.2022.960419

Cite this

Voros, S., Bansal, A. T., Barnes, M. R., Narula, J., Maurovich-Horvat, P., Vazquez, G., Marvasty, I. B., Brown, B. O., Voros, I. D., Harris, W., Voros, V., Dayspring, T., Neff, D., Greenfield, A., Furchtgott, L., Church, B., Runge, K., Khalil, I., Hayete, B., ... Newton, R. S. (2023). Bayesian network analysis of panomic biological big data identifies the importance of triglyceride-rich LDL in atherosclerosis development. Frontiers in Cardiovascular Medicine, 9, Article 960419. https://doi.org/10.3389/fcvm.2022.960419

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abstract = "Introduction: We sought to explore biomarkers of coronary atherosclerosis in an unbiased fashion. Methods: We analyzed 665 patients (mean ± SD age, 56 ± 11 years; 47\% male) from the GLOBAL clinical study (NCT01738828). Cases were defined by the presence of any discernable atherosclerotic plaque based on comprehensive cardiac computed tomography (CT). De novo Bayesian networks built out of 37,000 molecular measurements and 99 conventional biomarkers per patient examined the potential causality of specific biomarkers. Results: Most highly ranked biomarkers by gradient boosting were interleukin-6, symmetric dimethylarginine, LDL-triglycerides [LDL-TG], apolipoprotein B48, palmitoleic acid, small dense LDL, alkaline phosphatase, and asymmetric dimethylarginine. In Bayesian analysis, LDL-TG was directly linked to atherosclerosis in over 95\% of the ensembles. Genetic variants in the genomic region encoding hepatic lipase (LIPC) were associated with LIPC gene expression, LDL-TG levels and with atherosclerosis. Discussion: Triglyceride-rich LDL particles, which can now be routinely measured with a direct homogenous assay, may play an important role in atherosclerosis development. Clinical trial registration: GLOBAL clinical study (Genetic Loci and the Burden of Atherosclerotic Lesions); [https://clinicaltrials.gov/ct2/show/NCT01738828?term=NCT01738828\&rank=1], identifier [NCT01738828].",

keywords = "Bayesian network analysis, LDL-triglycerides, cardiovascular risk, hepatic lipase, omics, triglyceride-rich LDL",

author = "Szilard Voros and Bansal, \{Aruna T.\} and Barnes, \{Michael R.\} and Jagat Narula and Pal Maurovich-Horvat and Gustavo Vazquez and Marvasty, \{Idean B.\} and Brown, \{Bradley O.\} and Voros, \{Isaac D.\} and William Harris and Viktor Voros and Thomas Dayspring and David Neff and Alex Greenfield and Leon Furchtgott and Bruce Church and Karl Runge and Iya Khalil and Boris Hayete and Diego Lucero and Remaley, \{Alan T.\} and Newton, \{Roger S.\}",

note = "Publisher Copyright: Copyright {\textcopyright} 2023 Voros, Bansal, Barnes, Narula, Maurovich-Horvat, Vazquez, Marvasty, Brown, Voros, Harris, Voros, Dayspring, Neff, Greenfield, Furchtgott, Church, Runge, Khalil, Hayete, Lucero, Remaley and Newton.",

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Voros, S, Bansal, AT, Barnes, MR, Narula, J, Maurovich-Horvat, P, Vazquez, G, Marvasty, IB, Brown, BO, Voros, ID, Harris, W, Voros, V, Dayspring, T, Neff, D, Greenfield, A, Furchtgott, L, Church, B, Runge, K, Khalil, I, Hayete, B, Lucero, D, Remaley, AT & Newton, RS 2023, 'Bayesian network analysis of panomic biological big data identifies the importance of triglyceride-rich LDL in atherosclerosis development', Frontiers in Cardiovascular Medicine, vol. 9, 960419. https://doi.org/10.3389/fcvm.2022.960419

TY - JOUR

T1 - Bayesian network analysis of panomic biological big data identifies the importance of triglyceride-rich LDL in atherosclerosis development

AU - Voros, Szilard

AU - Bansal, Aruna T.

AU - Barnes, Michael R.

AU - Narula, Jagat

AU - Maurovich-Horvat, Pal

AU - Vazquez, Gustavo

AU - Marvasty, Idean B.

AU - Brown, Bradley O.

AU - Voros, Isaac D.

AU - Harris, William

AU - Voros, Viktor

AU - Dayspring, Thomas

AU - Neff, David

AU - Greenfield, Alex

AU - Furchtgott, Leon

AU - Church, Bruce

AU - Runge, Karl

AU - Khalil, Iya

AU - Hayete, Boris

AU - Lucero, Diego

AU - Remaley, Alan T.

AU - Newton, Roger S.

N1 - Publisher Copyright: Copyright © 2023 Voros, Bansal, Barnes, Narula, Maurovich-Horvat, Vazquez, Marvasty, Brown, Voros, Harris, Voros, Dayspring, Neff, Greenfield, Furchtgott, Church, Runge, Khalil, Hayete, Lucero, Remaley and Newton.

PY - 2023/1/4

Y1 - 2023/1/4

N2 - Introduction: We sought to explore biomarkers of coronary atherosclerosis in an unbiased fashion. Methods: We analyzed 665 patients (mean ± SD age, 56 ± 11 years; 47% male) from the GLOBAL clinical study (NCT01738828). Cases were defined by the presence of any discernable atherosclerotic plaque based on comprehensive cardiac computed tomography (CT). De novo Bayesian networks built out of 37,000 molecular measurements and 99 conventional biomarkers per patient examined the potential causality of specific biomarkers. Results: Most highly ranked biomarkers by gradient boosting were interleukin-6, symmetric dimethylarginine, LDL-triglycerides [LDL-TG], apolipoprotein B48, palmitoleic acid, small dense LDL, alkaline phosphatase, and asymmetric dimethylarginine. In Bayesian analysis, LDL-TG was directly linked to atherosclerosis in over 95% of the ensembles. Genetic variants in the genomic region encoding hepatic lipase (LIPC) were associated with LIPC gene expression, LDL-TG levels and with atherosclerosis. Discussion: Triglyceride-rich LDL particles, which can now be routinely measured with a direct homogenous assay, may play an important role in atherosclerosis development. Clinical trial registration: GLOBAL clinical study (Genetic Loci and the Burden of Atherosclerotic Lesions); [https://clinicaltrials.gov/ct2/show/NCT01738828?term=NCT01738828&rank=1], identifier [NCT01738828].

AB - Introduction: We sought to explore biomarkers of coronary atherosclerosis in an unbiased fashion. Methods: We analyzed 665 patients (mean ± SD age, 56 ± 11 years; 47% male) from the GLOBAL clinical study (NCT01738828). Cases were defined by the presence of any discernable atherosclerotic plaque based on comprehensive cardiac computed tomography (CT). De novo Bayesian networks built out of 37,000 molecular measurements and 99 conventional biomarkers per patient examined the potential causality of specific biomarkers. Results: Most highly ranked biomarkers by gradient boosting were interleukin-6, symmetric dimethylarginine, LDL-triglycerides [LDL-TG], apolipoprotein B48, palmitoleic acid, small dense LDL, alkaline phosphatase, and asymmetric dimethylarginine. In Bayesian analysis, LDL-TG was directly linked to atherosclerosis in over 95% of the ensembles. Genetic variants in the genomic region encoding hepatic lipase (LIPC) were associated with LIPC gene expression, LDL-TG levels and with atherosclerosis. Discussion: Triglyceride-rich LDL particles, which can now be routinely measured with a direct homogenous assay, may play an important role in atherosclerosis development. Clinical trial registration: GLOBAL clinical study (Genetic Loci and the Burden of Atherosclerotic Lesions); [https://clinicaltrials.gov/ct2/show/NCT01738828?term=NCT01738828&rank=1], identifier [NCT01738828].

KW - Bayesian network analysis

KW - LDL-triglycerides

KW - cardiovascular risk

KW - hepatic lipase

KW - omics

KW - triglyceride-rich LDL

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UR - https://www.scopus.com/pages/publications/85146483741#tab=citedBy

U2 - 10.3389/fcvm.2022.960419

DO - 10.3389/fcvm.2022.960419

M3 - Article

AN - SCOPUS:85146483741

SN - 2297-055X

VL - 9

JO - Frontiers in Cardiovascular Medicine

JF - Frontiers in Cardiovascular Medicine

M1 - 960419

ER -

Bayesian network analysis of panomic biological big data identifies the importance of triglyceride-rich LDL in atherosclerosis development

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

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