Multi-Omics Investigation into Acute Myocardial Infarction: An Integrative Method Revealing Interconnections amongst the Metabolome, Lipidome, Glycome, and Metallome
Acute myocardial infarction (AMI) is a leading cause of mortality and morbidity worldwide. This work aims to investigate the translational potential of a multi-omics study (comprising metabolomics, lipidomics, glycomics, and metallomics) in revealing biomechanistic insights into AMI. Following the N...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-11-01
|
| Series: | Metabolites |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-1989/12/11/1080 |
| _version_ | 1827646060463390720 |
|---|---|
| author | Si Ying Lim Felicia Li Shea Lim Inmaculada Criado-Navarro Xin Hao Yeo Hiranya Dayal Sri Dhruti Vemulapalli Song Jie Seah Anna Karen Carrasco Laserna Xiaoxun Yang Sock Hwee Tan Mark Y. Chan Sam Fong Yau Li |
| author_facet | Si Ying Lim Felicia Li Shea Lim Inmaculada Criado-Navarro Xin Hao Yeo Hiranya Dayal Sri Dhruti Vemulapalli Song Jie Seah Anna Karen Carrasco Laserna Xiaoxun Yang Sock Hwee Tan Mark Y. Chan Sam Fong Yau Li |
| author_sort | Si Ying Lim |
| collection | DOAJ |
| description | Acute myocardial infarction (AMI) is a leading cause of mortality and morbidity worldwide. This work aims to investigate the translational potential of a multi-omics study (comprising metabolomics, lipidomics, glycomics, and metallomics) in revealing biomechanistic insights into AMI. Following the N-glycomics and metallomics studies performed by our group previously, untargeted metabolomic and lipidomic profiles were generated and analysed in this work via the use of a simultaneous metabolite/lipid extraction and liquid chromatography–tandem mass spectrometry (LC–MS/MS) analysis workflow. The workflow was applied to blood plasma samples from AMI cases (<i>n</i> = 101) and age-matched healthy controls (<i>n</i> = 66). The annotated metabolomic (number of features, <i>n</i> = 27) and lipidomic (<i>n</i> = 48) profiles, along with the glycomic (<i>n</i> = 37) and metallomic (<i>n</i> = 30) profiles of the same set of AMI and healthy samples were integrated and analysed. The integration method used here works by identifying a linear combination of maximally correlated features across the four omics datasets, via utilising both block-partial least squares-discriminant analysis (block-PLS-DA) based on sparse generalised canonical correlation analysis. Based on the multi-omics mapping of biomolecular interconnections, several postulations were derived. These include the potential roles of glycerophospholipids in N-glycan-modulated immunoregulatory effects, as well as the augmentation of the importance of Ca–ATPases in cardiovascular conditions, while also suggesting contributions of phosphatidylethanolamine in their functions. Moreover, it was shown that combining the four omics datasets synergistically enhanced the classifier performance in discriminating between AMI and healthy subjects. Fresh and intriguing insights into AMI, otherwise undetected via single-omics analysis, were revealed in this multi-omics study. Taken together, we provide evidence that a multi-omics strategy may synergistically reinforce and enhance our understanding of diseases. |
| first_indexed | 2024-03-09T18:50:44Z |
| format | Article |
| id | doaj.art-420cfbc4afa444dab92c6c1e6942f41e |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-09T18:50:44Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-420cfbc4afa444dab92c6c1e6942f41e2023-11-24T05:50:40ZengMDPI AGMetabolites2218-19892022-11-011211108010.3390/metabo12111080Multi-Omics Investigation into Acute Myocardial Infarction: An Integrative Method Revealing Interconnections amongst the Metabolome, Lipidome, Glycome, and MetallomeSi Ying Lim0Felicia Li Shea Lim1Inmaculada Criado-Navarro2Xin Hao Yeo3Hiranya Dayal4Sri Dhruti Vemulapalli5Song Jie Seah6Anna Karen Carrasco Laserna7Xiaoxun Yang8Sock Hwee Tan9Mark Y. Chan10Sam Fong Yau Li11NUS Graduate School’s Integrative Sciences & Engineering Programme (ISEP), National University of Singapore, Singapore 119077, SingaporeDepartment of Chemistry, National University of Singapore, Singapore 117543, SingaporeDepartment of Chemistry, National University of Singapore, Singapore 117543, SingaporeDepartment of Chemistry, National University of Singapore, Singapore 117543, SingaporeDepartment of Chemistry, National University of Singapore, Singapore 117543, SingaporeDepartment of Chemistry, National University of Singapore, Singapore 117543, SingaporeDepartment of Chemistry, National University of Singapore, Singapore 117543, SingaporeDepartment of Chemistry, National University of Singapore, Singapore 117543, SingaporeCardiovascular Research Institute, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, SingaporeCardiovascular Research Institute, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, SingaporeCardiovascular Research Institute, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, SingaporeNUS Graduate School’s Integrative Sciences & Engineering Programme (ISEP), National University of Singapore, Singapore 119077, SingaporeAcute myocardial infarction (AMI) is a leading cause of mortality and morbidity worldwide. This work aims to investigate the translational potential of a multi-omics study (comprising metabolomics, lipidomics, glycomics, and metallomics) in revealing biomechanistic insights into AMI. Following the N-glycomics and metallomics studies performed by our group previously, untargeted metabolomic and lipidomic profiles were generated and analysed in this work via the use of a simultaneous metabolite/lipid extraction and liquid chromatography–tandem mass spectrometry (LC–MS/MS) analysis workflow. The workflow was applied to blood plasma samples from AMI cases (<i>n</i> = 101) and age-matched healthy controls (<i>n</i> = 66). The annotated metabolomic (number of features, <i>n</i> = 27) and lipidomic (<i>n</i> = 48) profiles, along with the glycomic (<i>n</i> = 37) and metallomic (<i>n</i> = 30) profiles of the same set of AMI and healthy samples were integrated and analysed. The integration method used here works by identifying a linear combination of maximally correlated features across the four omics datasets, via utilising both block-partial least squares-discriminant analysis (block-PLS-DA) based on sparse generalised canonical correlation analysis. Based on the multi-omics mapping of biomolecular interconnections, several postulations were derived. These include the potential roles of glycerophospholipids in N-glycan-modulated immunoregulatory effects, as well as the augmentation of the importance of Ca–ATPases in cardiovascular conditions, while also suggesting contributions of phosphatidylethanolamine in their functions. Moreover, it was shown that combining the four omics datasets synergistically enhanced the classifier performance in discriminating between AMI and healthy subjects. Fresh and intriguing insights into AMI, otherwise undetected via single-omics analysis, were revealed in this multi-omics study. Taken together, we provide evidence that a multi-omics strategy may synergistically reinforce and enhance our understanding of diseases.https://www.mdpi.com/2218-1989/12/11/1080multi-omicsmetabolomicslipidomicsglycomicsmetallomicsacute myocardial infarction |
| spellingShingle | Si Ying Lim Felicia Li Shea Lim Inmaculada Criado-Navarro Xin Hao Yeo Hiranya Dayal Sri Dhruti Vemulapalli Song Jie Seah Anna Karen Carrasco Laserna Xiaoxun Yang Sock Hwee Tan Mark Y. Chan Sam Fong Yau Li Multi-Omics Investigation into Acute Myocardial Infarction: An Integrative Method Revealing Interconnections amongst the Metabolome, Lipidome, Glycome, and Metallome Metabolites multi-omics metabolomics lipidomics glycomics metallomics acute myocardial infarction |
| title | Multi-Omics Investigation into Acute Myocardial Infarction: An Integrative Method Revealing Interconnections amongst the Metabolome, Lipidome, Glycome, and Metallome |
| title_full | Multi-Omics Investigation into Acute Myocardial Infarction: An Integrative Method Revealing Interconnections amongst the Metabolome, Lipidome, Glycome, and Metallome |
| title_fullStr | Multi-Omics Investigation into Acute Myocardial Infarction: An Integrative Method Revealing Interconnections amongst the Metabolome, Lipidome, Glycome, and Metallome |
| title_full_unstemmed | Multi-Omics Investigation into Acute Myocardial Infarction: An Integrative Method Revealing Interconnections amongst the Metabolome, Lipidome, Glycome, and Metallome |
| title_short | Multi-Omics Investigation into Acute Myocardial Infarction: An Integrative Method Revealing Interconnections amongst the Metabolome, Lipidome, Glycome, and Metallome |
| title_sort | multi omics investigation into acute myocardial infarction an integrative method revealing interconnections amongst the metabolome lipidome glycome and metallome |
| topic | multi-omics metabolomics lipidomics glycomics metallomics acute myocardial infarction |
| url | https://www.mdpi.com/2218-1989/12/11/1080 |
| work_keys_str_mv | AT siyinglim multiomicsinvestigationintoacutemyocardialinfarctionanintegrativemethodrevealinginterconnectionsamongstthemetabolomelipidomeglycomeandmetallome AT felicialishealim multiomicsinvestigationintoacutemyocardialinfarctionanintegrativemethodrevealinginterconnectionsamongstthemetabolomelipidomeglycomeandmetallome AT inmaculadacriadonavarro multiomicsinvestigationintoacutemyocardialinfarctionanintegrativemethodrevealinginterconnectionsamongstthemetabolomelipidomeglycomeandmetallome AT xinhaoyeo multiomicsinvestigationintoacutemyocardialinfarctionanintegrativemethodrevealinginterconnectionsamongstthemetabolomelipidomeglycomeandmetallome AT hiranyadayal multiomicsinvestigationintoacutemyocardialinfarctionanintegrativemethodrevealinginterconnectionsamongstthemetabolomelipidomeglycomeandmetallome AT sridhrutivemulapalli multiomicsinvestigationintoacutemyocardialinfarctionanintegrativemethodrevealinginterconnectionsamongstthemetabolomelipidomeglycomeandmetallome AT songjieseah multiomicsinvestigationintoacutemyocardialinfarctionanintegrativemethodrevealinginterconnectionsamongstthemetabolomelipidomeglycomeandmetallome AT annakarencarrascolaserna multiomicsinvestigationintoacutemyocardialinfarctionanintegrativemethodrevealinginterconnectionsamongstthemetabolomelipidomeglycomeandmetallome AT xiaoxunyang multiomicsinvestigationintoacutemyocardialinfarctionanintegrativemethodrevealinginterconnectionsamongstthemetabolomelipidomeglycomeandmetallome AT sockhweetan multiomicsinvestigationintoacutemyocardialinfarctionanintegrativemethodrevealinginterconnectionsamongstthemetabolomelipidomeglycomeandmetallome AT markychan multiomicsinvestigationintoacutemyocardialinfarctionanintegrativemethodrevealinginterconnectionsamongstthemetabolomelipidomeglycomeandmetallome AT samfongyauli multiomicsinvestigationintoacutemyocardialinfarctionanintegrativemethodrevealinginterconnectionsamongstthemetabolomelipidomeglycomeandmetallome |