Multi-ethnic Imputation System (MI-System): A genotype imputation server for high-dimensional data

Amrita Chattopadhyay; Chien-Yueh Lee; Ying-Cheng Shen; Kuan-Chen Lu; Tzu-Hung Hsiao; Ching-Heng Lin; Liang-Chuan Lai; Mong-Hsun Tsai; Tzu-Pin Lu; Eric Y Chuang

doi:10.1016/j.jbi.2023.104423

Multi-ethnic Imputation System (MI-System): A genotype imputation server for high-dimensional data

J Biomed Inform. 2023 Jul:143:104423. doi: 10.1016/j.jbi.2023.104423. Epub 2023 Jun 10.

Authors

Affiliations

¹ Bioinformatics and Biostatistics Core, Centre of Genomic and Precision Medicine, National Taiwan University, Taipei, Taiwan.
² Department of Biomedical Engineering, College of Biomedical Engineering, China Medical University, Taichung, Taiwan.
³ Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan.
⁴ Department of Public Health, Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan.
⁵ Department of Medical Research, Taichung Veterans General Hospital, Taiwan.
⁶ Bioinformatics and Biostatistics Core, Centre of Genomic and Precision Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Physiology, College of Medicine, National Taiwan University, Taipei, Taiwan.
⁷ Bioinformatics and Biostatistics Core, Centre of Genomic and Precision Medicine, National Taiwan University, Taipei, Taiwan; Institute of Biotechnology, National Taiwan University, Taipei, Taiwan; Center of Biotechnology, National Taiwan University, Taipei, Taiwan.
⁸ Bioinformatics and Biostatistics Core, Centre of Genomic and Precision Medicine, National Taiwan University, Taipei, Taiwan; Department of Public Health, Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan; Institute of Health Data Analytics and Statistics, National Taiwan University, Taipei, Taiwan; Population Health Research Center, National Taiwan University, Taipei, Taiwan. Electronic address: tplu@ntu.edu.tw.
⁹ Bioinformatics and Biostatistics Core, Centre of Genomic and Precision Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan; Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu, Taiwan. Electronic address: chuangey@ntu.edu.tw.

PMID: 37308034
DOI: 10.1016/j.jbi.2023.104423

Abstract

Objective: Genotype imputation is a commonly used technique that infers un-typed variants into a study's genotype data, allowing better identification of causal variants in disease studies. However, due to overrepresentation of Caucasian studies, there's a lack of understanding of genetic basis of health-outcomes in other ethnic populations. Therefore, facilitating imputation of missing key-predictor-variants that can potentially improve a risk health-outcome prediction model, specifically for Asian ancestry, is of utmost relevance.

Methods: We aimed to construct an imputation and analysis web-platform, that primarily facilitates, but is not limited to genotype imputation on East-Asians. The goal is to provide a collaborative imputation platform for researchers in the public domain towards rapidly and efficiently conducting accurate genotype imputation.

Results: We present an online genotype imputation platform, Multi-ethnic Imputation System (MI-System) (https://misystem.cgm.ntu.edu.tw/), that offers users 3 established pipelines, SHAPEIT2-IMPUTE2, SHAPEIT4-IMPUTE5, and Beagle5.1 for conducting imputation analyses. In addition to 1000 Genomes and Hapmap3, a new customized Taiwan Biobank (TWB) reference panel, specifically created for Taiwanese-Chinese ancestry is provided. MI-System further offers functions to create customized reference panels to be used for imputation, conduct quality control, split whole genome data into chromosomes, and convert genome builds.

Conclusion: Users can upload their genotype data and perform imputation with minimum effort and resources. The utility functions further can be utilized to preprocess user uploaded data with easy clicks. MI-System potentially contributes to Asian-population genetics research, while eliminating the requirement for high performing computational resources and bioinformatics expertise. It will enable an increased pace of research and provide a knowledge-base for genetic carriers of complex diseases, therefore greatly enhancing patient-driven research.

Statement of significance: Multi-ethnic Imputation System (MI-System), primarily facilitates, but is not limited to, imputation on East-Asians, through 3 established prephasing-imputation pipelines, SHAPEIT2-IMPUTE2, SHAPEIT4-IMPUTE5, and Beagle5.1, where users can upload their genotype data and perform imputation and other utility functions with minimum effort and resources. A new customized Taiwan Biobank (TWB) reference panel, specifically created for Taiwanese-Chinese ancestry is provided. Utility functions include (a) create customized reference panels, (b) conduct quality control, (c) split whole genome data into chromosomes, and (d) convert genome builds. Users can also combine 2 reference panels using the system and use combined panels as reference to conduct imputation using MI-System.

Keywords: Beagle5.1; Genotype imputation; IMPUTE2; IMPUTE5; Taiwan biobank; Web-server.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Computers
Gene Frequency
Genetics, Population*
Genome*
Genome-Wide Association Study
Genotype
Humans
Polymorphism, Single Nucleotide