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

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.

Mono or Dual Antiplatelet Therapy for Treating Patients with Peripheral Artery Disease after Lower Extremity Revascularization: A Systematic Review and Meta-Analysis

“…The application of the study results, which were obtained using Caucasian populations, to other ethnic populations is questionable. Asian populations have a higher level of clopidogrel resistance [ 50 , 51 , 52 ]. In our pooled studies, most of the combinations used for the DAPTs involve clopidogrel plus aspirin.…”

The Role of BTBD7 in Normal Development and Tumor Progression

“…They are involved in mitochondrial autophagy and DNA repair pathways, accelerating the healing process of CAD. However, when the BTBD7 gene acts alone, it is engaged in clopidogrel resistance, leading to treatment failure in peripheral arterial disease 57 (Figure 1). Thus, BTBD7 may be an independent predictor of CAD.…”

Cardiovascular/Stroke Risk Stratification in Parkinson’s Disease Patients Using Atherosclerosis Pathway and Artificial Intelligence Paradigm: A Systematic Review

“…Machine learning has been a powerful paradigm since it uses a knowledge-based model for building the training system. Recently, there have been attempts to design ML systems covering several applications such as diabetes [59,60,165], neonatology [166], gene [167,168], coronary artery disease risk stratification [169,170], carotid plaque classification [171], cancer imaging such as thyroid [61,172,173], breast [174], ovarian [64,175], prostate [63,176], etc. The second key benefit of ML is its ability to handle the nonlinearity between the combination of risk factors (or covariates) and the gold standard.…”