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

Front Cardiovasc Med. 2023 Jan 4:9:960419. doi: 10.3389/fcvm.2022.960419. eCollection 2022.

Authors

Szilard Voros¹, Aruna T Bansal², Michael R Barnes², Jagat Narula³, Pal Maurovich-Horvat⁴, Gustavo Vazquez⁵, Idean B Marvasty¹, Bradley O Brown¹, Isaac D Voros¹, William Harris⁶, Viktor Voros^{1

7}, Thomas Dayspring⁵, David Neff¹, Alex Greenfield⁸, Leon Furchtgott⁸, Bruce Church⁸, Karl Runge⁸, Iya Khalil⁸, Boris Hayete⁸, Diego Lucero⁹, Alan T Remaley⁹, Roger S Newton¹

Affiliations

¹ Global Genomics Group, Atlanta, GA, United States.
² Acclarogen, Ltd, Cambridge, United Kingdom.
³ Mount Sinai School of Medicine, New York, NY, United States.
⁴ MTA-SE Cardiovascular Imaging Research Group, Heart and Vascular Center, Semmelweis University, Budapest, Hungary.
⁵ Global Institute for Research, LLC, Richmond, VA, United States.
⁶ OmegaQuant, Sioux Falls, SD, United States.
⁷ Department of Psychiatry, Medical School, University of Pécs, Pécs, Hungary.
⁸ GNS Healthcare, Somerville, MA, United States.
⁹ Lipoprotein Metabolism Laboratory, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, United States.

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.

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.