ABSTRACT
A genome-wide association study (GWAS) can be conducted to systematically analyze the contributions of genetic factors to a wide variety of complex diseases. Nevertheless, existing GWASs have provided highly ethnic specific data. Accordingly, to provide data specific to Taiwan, we established a large-scale genetic database in a single medical institution at the China Medical University Hospital. With current technological limitations, microarray analysis can detect only a limited number of single-nucleotide polymorphisms (SNPs) with a minor allele frequency of >1%. Nevertheless, imputation represents a useful alternative means of expanding data. In this study, we compared four imputation algorithms in terms of various metrics. We observed that among the compared algorithms, Beagle5.2 achieved the fastest calculation speed, smallest storage space, highest specificity, and highest number of high-quality variants. We obtained 15,277,414 high-quality variants in 175,871 people by using Beagle5.2. In our internal verification process, Beagle5.2 exhibited an accuracy rate of up to 98.75%. We also conducted external verification. Our imputed variants had a 79.91% mapping rate and 90.41% accuracy. These results will be combined with clinical data in future research. We have made the results available for researchers to use in formulating imputation algorithms, in addition to establishing a complete SNP database for GWAS and PRS researchers. We believe that these data can help improve overall medical capabilities, particularly precision medicine, in Taiwan.
ABSTRACT
VarioWatch (http://genepipe.ncgm.sinica.edu.tw/variowatch/) has been vastly improved since its former publication GenoWatch in the 2008 Web Server Issue. It is now at least 10 000-times faster in annotating a variant. Drastic speed increase, through complete re-design of its working mechanism, makes VarioWatch capable of annotating millions of human genomic variants generated from next generation sequencing in minutes, if not seconds. While using MegaQuery of VarioWatch to quickly annotate variants, users can apply various filters to retrieve a subgroup of variants according to the risk levels, interested regions, etc. that satisfy users' requirements. In addition to performance leap, many new features have also been added, such as annotation on novel variants, functional analyses on splice sites and in/dels, detailed variant information in tabulated form, plus a risk level decision tree regarding the analyzed variant. Up to 1000 target variants can be visualized with our carefully designed Genome View, Gene View, Transcript View and Variation View. Two commonly used reference versions, NCBI build 36.3 and NCBI build 37.2, are supported. VarioWatch is unique in its ability to annotate comprehensively and efficiently millions of variants online, immediately delivering the results in real time, plus visualizes up to 1000 annotated variants.
