Mapping gene and gene pathways associated with coronary artery disease: a CARDIoGRAM exome and multi-ancestry UK biobank analysis

Hariharan, Praveen; Dupuis, Josée

doi:10.1038/s41598-021-95637-9

Cited by 4 publications

(3 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…DUSP13 was associated with the regulation of the MAPK signaling pathway after stress stimulation in cardiomyocytes [ 35 ]. The up-regulation of DUSP13 to cardiac stress contributed to coronary artery disease, a common cardiovascular comorbidity of COVID-19 [ 36 , 37 ]. UNC5A retrained virus replication through autophagy induction instead of apoptosis [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

A Novel 3-Gene Signature for Identifying COVID-19 Patients Based on Bioinformatics and Machine Learning

Lai

Liu

Deng

et al. 2022

Genes

View full text Add to dashboard Cite

Although many biomarkers associated with coronavirus disease 2019 (COVID-19) were found, a novel signature relevant to immune cells has not been developed. In this work, the “CIBERSORT” algorithm was used to assess the fraction of immune infiltrating cells in GSE152641 and GSE171110. Key modules associated with important immune cells were selected by the “WGCNA” package. The “GO” enrichment analysis was used to reveal the biological function associated with COVID-19. The “Boruta” algorithm was used to screen candidate genes, and the “LASSO” algorithm was used for collinearity reduction. A novel gene signature was developed based on multivariate logistic regression analysis. Subsequently, M0 macrophages (PRAUC = 0.948 in GSE152641 and PRAUC = 0.981 in GSE171110) and neutrophils (PRAUC = 0.892 in GSE152641 and PRAUC = 0.960 in GSE171110) were considered as important immune cells. Forty-three intersected genes from two modules were selected, which mainly participated in some immune-related activities. Finally, a three-gene signature comprising CLEC4D, DUSP13, and UNC5A that can accurately distinguish COVID-19 patients and healthy controls in three datasets was constructed. The ROCAUC was 0.974 in the training set, 0.946 in the internal test set, and 0.709 in the external test set. In conclusion, we constructed a three-gene signature to identify COVID-19, and CLEC4D, DUSP13, and UNC5A may be potential biomarkers for COVID-19 patients.

show abstract

Section: Discussionmentioning

confidence: 99%

A Novel 3-Gene Signature for Identifying COVID-19 Patients Based on Bioinformatics and Machine Learning

Lai

Liu

Deng

et al. 2022

Genes

View full text Add to dashboard Cite

show abstract

“…In FAM177B , we identified a variant (I3S) that corresponded with increased risk (OR, 1.18) and has recently been associated with CAD in a gene‐based meta‐analysis along with the substitution Q523R in MST1R . 76 These data illustrate that the 79 candidate genes are clinically important by increasing or decreasing the relative risk of EOMI and reveal variants of potentially novel mechanistic interest.…”

Section: Resultsmentioning

confidence: 88%

“… 109 , 110 Our analyses showed that MST1R is connected in STRING to EPOR , a regulator of JAK2 (Figure 2E ), and contains a single nucleotide polymorphism that is directly associated with increased EOMI risk (R1335G; OR, 1.15; EA=43.52) (Figure 3B ). MST1R has recently been identified by gene‐based association tests for CAD, 76 and MST1R null mice have impaired nitric oxide levels and increased tissue damage in response to acute stress. 111 Third, DHX58 represents a previously reported yet understudied association in the context of CAD.…”

Section: Discussionmentioning

confidence: 99%

Evolutionary Action–Machine Learning Model Identifies Candidate Genes Associated With Early‐Onset Coronary Artery Disease

Shapiro,

Lee,

Asmussen

et al. 2023

JAHA

View full text Add to dashboard Cite

Background Coronary artery disease is a primary cause of death around the world, with both genetic and environmental risk factors. Although genome‐wide association studies have linked >100 unique loci to its genetic basis, these only explain a fraction of disease heritability. Methods and Results To find additional gene drivers of coronary artery disease, we applied machine learning to quantitative evolutionary information on the impact of coding variants in whole exomes from the Myocardial Infarction Genetics Consortium. Using ensemble‐based supervised learning, the Evolutionary Action–Machine Learning framework ranked each gene's ability to classify case and control samples and identified 79 significant associations. These were connected to known risk loci; enriched in cardiovascular processes like lipid metabolism, blood clotting, and inflammation; and enriched for cardiovascular phenotypes in knockout mouse models. Among them, INPP5F and MST1R are examples of potentially novel coronary artery disease risk genes that modulate immune signaling in response to cardiac stress. Conclusions We concluded that machine learning on the functional impact of coding variants, based on a massive amount of evolutionary information, has the power to suggest novel coronary artery disease risk genes for mechanistic and therapeutic discoveries in cardiovascular biology, and should also apply in other complex polygenic diseases.

show abstract

MOB3A Bypasses BRAF and RAS Oncogene-Induced Senescence by Engaging the Hippo Pathway

Dutchak

Garnett

Nicoll

et al. 2022

Molecular Cancer Research

View full text Add to dashboard Cite

Oncogenic activation of the RTK–RAS–RAF–MEK–ERK pathway occurs in approximately 25% of all human cancers, yet activated RAS, BRAF, or MEK expression in primary cells leads to a prolonged and predominantly irreversible cell-cycle arrest termed oncogene-induced senescence (OIS). OIS acts as an intrinsic tumor suppressor mechanism, serving as a barrier to tumor progression. Screening a library of activated kinases and kinase-regulatory proteins we identified MOB3A, a Mps-one binder coactivator (MOB) protein family member, whose constitutive expression permits proliferation and suppresses senescence in response to oncogenic RAS and BRAF signals. MOB3A is one of seven human MOB genes, which are highly conserved from yeast to human and that function to activate the Hippo pathway kinases (MST/LATS) or NDR kinases through direct association. Here we show that within the MOB family of genes MOB3A and C are unique in their ability to allow primary cell proliferation in the face of sustained oncogene signaling. Unlike the canonical MOB1A/B proteins, MOB3A inhibits Hippo/MST/LATS signaling and constitutive MOB3A membrane localization phenocopies OIS bypass seen with elevated YAP expression. Moreover, inhibition of MOB3 family member expression results in decreased proliferation and tumor growth of cancer cell lines. Together these data identify MOB3A's role in bypass of oncogene induced senescence and its role as a Hippo pathway inhibitor. Implications: These results suggest that MOB3 targeting to re-engage the Hippo pathway, or direct targeting of YAP/TAZ, may be viable therapeutic strategies potential for RAS-pathway driven tumours.

show abstract

Mapping gene and gene pathways associated with coronary artery disease: a CARDIoGRAM exome and multi-ancestry UK biobank analysis

Cited by 4 publications

References 69 publications

A Novel 3-Gene Signature for Identifying COVID-19 Patients Based on Bioinformatics and Machine Learning

A Novel 3-Gene Signature for Identifying COVID-19 Patients Based on Bioinformatics and Machine Learning

Evolutionary Action–Machine Learning Model Identifies Candidate Genes Associated With Early‐Onset Coronary Artery Disease

MOB3A Bypasses BRAF and RAS Oncogene-Induced Senescence by Engaging the Hippo Pathway

Contact Info

Product

Resources

About