Document Details

Document Type : Article In Journal 
Document Title :
Evolutionary Diagnosis of non-synonymous variants involved in differential drug response
Evolutionary Diagnosis of non-synonymous variants involved in differential drug response
 
Document Language : English 
Abstract : BACKGROUND: Many pharmaceutical drugs are known to be ineffective or have negative side effects in a substantial proportion of patients. Genomic advances are revealing that some non-synonymous single nucleotide variants (nsSNVs) may cause differences in drug efficacy and side effects. Therefore, it is desirable to evaluate nsSNVs of interest in their ability to modulate the drug response. RESULTS: We found that the available data on the link between drug response and nsSNV is rather modest. There were only 31 distinct drug response-altering (DR-altering) and 43 distinct drug response-neutral (DR-neutral) nsSNVs in the whole Pharmacogenomics Knowledge Base (PharmGKB). However, even with this modest dataset, it was clear that existing bioinformatics tools have difficulties in correctly predicting the known DR-altering and DR-neutral nsSNVs. They exhibited an overall accuracy of less than 50%, which was not better than random diagnosis. We found that the underlying problem is the markedly different evolutionary properties between positions harboring nsSNVs linked to drug responses and those observed for inherited diseases. To solve this problem, we developed a new diagnosis method, Drug-EvoD, which was trained on the evolutionary properties of nsSNVs associated with drug responses in a sparse learning framework. Drug-EvoD achieves a TPR of 84% and a TNR of 53%, with a balanced accuracy of 69%, which improves upon other methods significantly. CONCLUSIONS: The new tool will enable researchers to computationally identify nsSNVs that may affect drug responses. However, much larger training and testing datasets are needed to develop more reliable and accurate tools. 
ISSN : 1658-5763 
Journal Name : Saudi Journal of Internal Medicine 
Volume : 5 
Issue Number : 1 
Publishing Year : 1436 AH
2015 AD 
Article Type : Article 
Added Date : Wednesday, April 20, 2016 

Researchers

Researcher Name (Arabic)Researcher Name (English)Researcher TypeDr GradeEmail
Nevin Z GerekGerek, Nevin ZInvestigator  
Li LiuLiu, Li Researcher  
Kristyn GeroldGerold, Kristyn Researcher  
Pegah BiparvaBiparva, Pegah Researcher  
Eric D ThomasThomas, Eric DResearcher  
Sudhir KumarKumar, Sudhir Researcher s.kumar@temple.edu

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