Artificial-Intelligence-Assisted Discovery of Genetic Factors for Precision Medicine of Antiplatelet Therapy in Diabetic Peripheral Artery Disease

An increased risk of cardiovascular events was identified in patients with peripheral artery disease (PAD). Clopidogrel is one of the most widely used antiplatelet medications. However, there are heterogeneous outcomes when clopidogrel is used to prevent cardiovascular events in PAD patients. Here,...

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Published inBiomedicines Vol. 10; no. 1; p. 116
Main Authors Yeh, Chi-Hsiao, Chou, Yi-Ju, Tsai, Tsung-Hsien, Hsu, Paul Wei-Che, Li, Chun-Hsien, Chan, Yun-Hsuan, Tsai, Shih-Feng, Ng, Soh-Ching, Chou, Kuei-Mei, Lin, Yu-Ching, Juan, Yu-Hsiang, Fu, Tieh-Cheng, Lai, Chi-Chun, Sytwu, Huey-Kang, Tsai, Ting-Fen
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 06.01.2022
MDPI
Subjects
Acute coronary syndromes
Amputation
Artificial intelligence
Aspirin
Blood platelets
Cardiovascular disease
Cardiovascular diseases
Clopidogrel
CYP2C19
Diabetes
Diabetes mellitus
diabetic peripheral artery disease
Endocytosis
Enzymes
Genetic factors
Genome-wide association studies
Genomes
Heart attacks
Ischemia
Patients
Precision medicine
Protein turnover
Single-nucleotide polymorphism
Therapeutic targets
ticagrelor
Vascular diseases
Vein & artery diseases
United States > US
Taiwan
clopidogrel
ticagrelor
CYP2C19
single nucleotide polymorphism
artificial intelligence
diabetic peripheral artery disease
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Abstract An increased risk of cardiovascular events was identified in patients with peripheral artery disease (PAD). Clopidogrel is one of the most widely used antiplatelet medications. However, there are heterogeneous outcomes when clopidogrel is used to prevent cardiovascular events in PAD patients. Here, we use an artificial intelligence (AI)-assisted methodology to identify genetic factors potentially involved in the clopidogrel-resistant mechanism, which is currently unclear. Several discoveries can be pinpointed. Firstly, a high proportion (>50%) of clopidogrel resistance was found among diabetic PAD patients in Taiwan. Interestingly, our result suggests that platelet function test-guided antiplatelet therapy appears to reduce the post-interventional occurrence of major adverse cerebrovascular and cardiac events in diabetic PAD patients. Secondly, AI-assisted genome-wide association study of a single-nucleotide polymorphism (SNP) database identified a SNP signature composed of 20 SNPs, which are mapped into 9 protein-coding genes (SLC37A2, IQSEC1, WASHC3, PSD3, BTBD7, GLIS3, PRDM11, LRBA1, and CNR1). Finally, analysis of the protein connectivity map revealed that LRBA, GLIS3, BTBD7, IQSEC1, and PSD3 appear to form a protein interaction network. Intriguingly, the genetic factors seem to pinpoint a pathway related to endocytosis and recycling of P2Y12 receptor, which is the drug target of clopidogrel. Our findings reveal that a combination of AI-assisted discovery of SNP signatures and clinical parameters has the potential to develop an ethnic-specific precision medicine for antiplatelet therapy in diabetic PAD patients.
AbstractList An increased risk of cardiovascular events was identified in patients with peripheral artery disease (PAD). Clopidogrel is one of the most widely used antiplatelet medications. However, there are heterogeneous outcomes when clopidogrel is used to prevent cardiovascular events in PAD patients. Here, we use an artificial intelligence (AI)-assisted methodology to identify genetic factors potentially involved in the clopidogrel-resistant mechanism, which is currently unclear. Several discoveries can be pinpointed. Firstly, a high proportion (>50%) of clopidogrel resistance was found among diabetic PAD patients in Taiwan. Interestingly, our result suggests that platelet function test-guided antiplatelet therapy appears to reduce the post-interventional occurrence of major adverse cerebrovascular and cardiac events in diabetic PAD patients. Secondly, AI-assisted genome-wide association study of a single-nucleotide polymorphism (SNP) database identified a SNP signature composed of 20 SNPs, which are mapped into 9 protein-coding genes (SLC37A2, IQSEC1, WASHC3, PSD3, BTBD7, GLIS3, PRDM11, LRBA1, and CNR1). Finally, analysis of the protein connectivity map revealed that LRBA, GLIS3, BTBD7, IQSEC1, and PSD3 appear to form a protein interaction network. Intriguingly, the genetic factors seem to pinpoint a pathway related to endocytosis and recycling of P2Y12 receptor, which is the drug target of clopidogrel. Our findings reveal that a combination of AI-assisted discovery of SNP signatures and clinical parameters has the potential to develop an ethnic-specific precision medicine for antiplatelet therapy in diabetic PAD patients.
Author Chan, Yun-Hsuan
Lai, Chi-Chun
Chou, Yi-Ju
Ng, Soh-Ching
Li, Chun-Hsien
Yeh, Chi-Hsiao
Tsai, Tsung-Hsien
Lin, Yu-Ching
Sytwu, Huey-Kang
Juan, Yu-Hsiang
Tsai, Ting-Fen
Chou, Kuei-Mei
Hsu, Paul Wei-Che
Tsai, Shih-Feng
Fu, Tieh-Cheng
AuthorAffiliation 5 Advanced Tech BU, Acer Inc., New Taipei City 221, Taiwan; vincent.tsai@acer.com (T.-H.T.); Zack.Li@acer.com (C.-H.L.); Linda.Chan@acer.com (Y.-H.C.)
3 Community Medicine Research Center, Chang Gung Memorial Hospital, Keelung 204, Taiwan
2 College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; yuching1221@cgmh.org.tw (Y.-C.L.); 8801131@cgmh.org.tw (Y.-H.J.); mr5598@cgmh.org.tw (T.-C.F.)
10 National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli 350, Taiwan
11 National Defense Medical Center, Department & Graduate Institute of Microbiology and Immunology, Taipei 114, Taiwan
12 Departments of Life Sciences and Institute of Genome Sciences, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
8 Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, Keelung 204, Taiwan
4 Institute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli 350, Taiwan; yjchou0810@nhri.edu.tw (Y.-J.C.);
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/35052795$$D View this record in MEDLINE/PubMed
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Keywords clopidogrel
ticagrelor
CYP2C19
single nucleotide polymorphism
artificial intelligence
diabetic peripheral artery disease
Language English
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SSID ssj0000913814
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Snippet An increased risk of cardiovascular events was identified in patients with peripheral artery disease (PAD). Clopidogrel is one of the most widely used...
SourceID doaj
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proquest
crossref
pubmed
SourceType Open Website
Open Access Repository
Aggregation Database
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StartPage 116
SubjectTerms Acute coronary syndromes
Amputation
Artificial intelligence
Aspirin
Blood platelets
Cardiovascular disease
Cardiovascular diseases
Clopidogrel
CYP2C19
Diabetes
Diabetes mellitus
diabetic peripheral artery disease
Endocytosis
Enzymes
Genetic factors
Genome-wide association studies
Genomes
Heart attacks
Ischemia
Patients
Precision medicine
Protein turnover
Single-nucleotide polymorphism
Therapeutic targets
ticagrelor
Vascular diseases
Vein & artery diseases
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Title Artificial-Intelligence-Assisted Discovery of Genetic Factors for Precision Medicine of Antiplatelet Therapy in Diabetic Peripheral Artery Disease
URI https://www.ncbi.nlm.nih.gov/pubmed/35052795
https://www.proquest.com/docview/2621272739
https://search.proquest.com/docview/2622285658
https://pubmed.ncbi.nlm.nih.gov/PMC8773099
https://doaj.org/article/ab0fbb6b97f64d179adcaa24ad358c34
Volume 10
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