VnD: a structure-centric database of disease-related SNPs and drugs

Abstract

Numerous genetic variations have been found to be related to human diseases. Significant portion of those affect the drug response as well by changing the protein structure and function. Therefore, it is crucial to understand the trilateral relationship among genomic variations, diseases and drugs. We present the variations and drugs (VnD), a consolidated database containing information on diseases, related genes and genetic variations, protein structures and drug information. VnD was built in three steps. First, we integrated various resources systematically to deduce catalogs of disease-related genes, single nucleotide polymorphisms (SNPs), protein mutations and relevant drugs. VnD contains 137 195 disease-related gene records (13 940 distinct genes) and 16 586 genetic variation records (1790 distinct variations). Next, we carried out structure modeling and docking simulation for wild-type and mutant proteins to examine the structural and functional consequences of non-synonymous SNPs in the drug-related genes. Conformational changes in 590 wild-type and 4437 mutant proteins from drug-related genes were included in our database. Finally, we investigated the structural and biochemical properties relevant to drug binding such as the distribution of SNPs in proximal protein pockets, thermo-chemical stability, interactions with drugs and physico-chemical properties. The VnD database, available at http://vnd.kobic.re.kr:8080/VnD/ or vandd.org, would be a useful platform for researchers studying the underlying mechanism for association among genetic variations, diseases and drugs.

Protein localization as a principal feature of the etiology and comorbidity of genetic diseases

“…We used the BioPortal ( http://bioportal.bioontology.org/ ) ( Noy et al, 2009 ) to construct OMIM-to-ICD code mapping using the UMLS ( Bodenreider, 2004 ). The ontologies of OMIM and ICD-9-CM were downloaded from the BioPortal, and then the disease terms in OMIM and ICD-9-CM were mapped to the concept unique identified (CUI) in UMLS taking disease synonyms into consideration ( Yang et al, 2011 ). Through this procedure, we mapped 488 ICD-9-CM codes to 527 OMIM diseases with 524 CUIs ( Supplementary File 6 ).…”

RNA-Seq Approach for Genetic Improvement of Meat Quality in Pig and Evolutionary Insight into the Substrate Specificity of Animal Carbonyl Reductases

“…For example, variations in non-coding regions often affect gene splicing, CpG methylation, transcription factor binding, or the sequence of noncoding RNA, leading to altered levels of gene expression [5] , [6] , [7] , [8] , [9] . Noticeably, variations in protein-coding regions give rise to nonsynonymous change in the amino acid sequence of the encoded protein and thus, are more likely to affect the protein structure and function [10] , [11] , probably leading to the critical effects on a phenotype of interest such as meat quality trait [12] . In addition, it has been estimated that 20–30% of nsSNVs affect protein function [13] , [14] .…”

Integrated Computational Approaches and Tools for Allosteric Drug Discovery

“…This opens the door to personalized medicine, where knowledge of drug-resistant and drug-sensitive SNPs can assist in the development of effective biomarkers [99] and allow treatments to be tailored to individual patients [102,103]. Furthermore, understanding structural changes caused by nsSNPs would enable the design of novel drugs to target these mutations and, thus, is key in advancing precision/personalized medicine [104,105]. One example can be given from stroke and stroke-related medications.…”