TY - JOUR
T1 - Multiomics Analysis Coupled with Text Mining Identify Novel Biomarker Candidates for Recurrent Cardiovascular Events
AU - Chalikiopoulou, Constantina
AU - Bizjan, Barbara Jenko
AU - Leventopoulos, George
AU - Smaili, Kalliopi
AU - Blagus, Tanja
AU - Menti, Ariadni
AU - Liopetas, John
AU - John, Anne
AU - Ali, Bassam R.
AU - Dolzan, Vita
AU - Hahalis, George N.
AU - Patrinos, George P.
AU - Katsila, Theodora
N1 - Funding Information:
We acknowledge support of this work by the project ‘‘INSPIRED—The National Research Infrastructures on Integrated Structural Biology, Drug Screening Efforts and Drug Target Functional Characterization’’ (Grant No. MIS 5002550), which is implemented under the Action ‘‘Reinforcement of the Research and Innovation Infrastructure,’’ funded by the Operational Programme ‘‘Competitiveness, Entrepreneurship and Innovation’’ (NSRF 2014–2020) and cofinanced by Greece and the European Union (European Regional Development Fund).
Publisher Copyright:
© Copyright 2020, Mary Ann Liebert, Inc.
PY - 2020/4
Y1 - 2020/4
N2 - Recurrent cardiovascular events remain an enigma that accounts for >30% of deaths worldwide. While heredity and human genetics variation play a key role, host-environment interactions offer a sound conceptual framework to dissect the molecular basis of recurrent cardiovascular events from genes and proteins to metabolites, thus accounting for environmental contributions as well. We report here a multiomics systems science approach so as to map interindividual variability in susceptibility to recurrent cardiovascular events. First, we performed data and text mining through a mixed-methods content analysis to select genomic variants, 10 single nucleotide polymorphisms, and microRNAs (miR-10a, miR-21, and miR-20a), minimizing bias in candidate marker selection. Next, we validated our in silico data in a patient cohort suffering from recurrent cardiovascular events (a cross-sectional study design and sampling). Our findings report a key role in low-density lipoprotein clearance for rs11206510 (p < 0.01) and rs515135 (p < 0.05). miR-10a (p < 0.05) was significantly associated with heart failure, while increased expression levels for miR-21 and miR-20a associated with atherosclerosis. In addition, liquid chromatography-mass spectrometry-based (LC-MS-based) proteomics analyses identified that vascular diameter and cholesterol levels are among the key factors to be considered in recurrent cardiovascular events. From a methodology innovation standpoint, this study offers a strategy to enhance the signal-to-noise ratios in mapping novel biomarker candidates wherein each research and conceptual step were interrogated for their validity and in turn, enriched one another, ideally translating information growth to knowledge growth.
AB - Recurrent cardiovascular events remain an enigma that accounts for >30% of deaths worldwide. While heredity and human genetics variation play a key role, host-environment interactions offer a sound conceptual framework to dissect the molecular basis of recurrent cardiovascular events from genes and proteins to metabolites, thus accounting for environmental contributions as well. We report here a multiomics systems science approach so as to map interindividual variability in susceptibility to recurrent cardiovascular events. First, we performed data and text mining through a mixed-methods content analysis to select genomic variants, 10 single nucleotide polymorphisms, and microRNAs (miR-10a, miR-21, and miR-20a), minimizing bias in candidate marker selection. Next, we validated our in silico data in a patient cohort suffering from recurrent cardiovascular events (a cross-sectional study design and sampling). Our findings report a key role in low-density lipoprotein clearance for rs11206510 (p < 0.01) and rs515135 (p < 0.05). miR-10a (p < 0.05) was significantly associated with heart failure, while increased expression levels for miR-21 and miR-20a associated with atherosclerosis. In addition, liquid chromatography-mass spectrometry-based (LC-MS-based) proteomics analyses identified that vascular diameter and cholesterol levels are among the key factors to be considered in recurrent cardiovascular events. From a methodology innovation standpoint, this study offers a strategy to enhance the signal-to-noise ratios in mapping novel biomarker candidates wherein each research and conceptual step were interrogated for their validity and in turn, enriched one another, ideally translating information growth to knowledge growth.
KW - biomarkers
KW - cardiovascular events
KW - genomics
KW - genotype and phenotype association
KW - miRNAs
KW - personalized medicine
KW - proteomics
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U2 - 10.1089/omi.2019.0216
DO - 10.1089/omi.2019.0216
M3 - Article
C2 - 32176569
AN - SCOPUS:85083543950
SN - 1536-2310
VL - 24
SP - 205
EP - 215
JO - OMICS A Journal of Integrative Biology
JF - OMICS A Journal of Integrative Biology
IS - 4
ER -