Genotype imputation server is established based on the high-quality BIGCS reference panel. Owing to the incorporation of family members, it can ensure more accurate genotype imputation for individuals of Han ancestry and enables precise long-range phasing.

The task of imputation using BIGCS Imputation Server can be readily handle through the following steps:

1) Input file format: a VCF file conforming to the GRCh38/hg38 coordinate. A demo VCF file is accessible for detailed examination and can be downloaded from: http://gdbig.bigcs.com.cn/static/downloads/demo/test.22.vcf.gz.

2) Reference Panel: We have constructed a BIGCS haplotype reference panel (BIGCS v1.0) which consists of 2,245 unrelated individuals and 43,055,086 high-quality SNPs along with 4,184,387 indels spanning the 22 autosomes and the X chromosome.

3) Imputation tools: Beagle 5.1 (https://faculty.washington.edu/browning/beagle/b5_1.html) was employed for phasing process and Minimac4 (https://github.com/statgen/Minimac4) was employed for imputation step with default parameters.

4) Check and approve the Agreement.

5) Submit job and download the result: Job details will be informed in a timely manner, and the notification email will remind the user of the task status.

Generally, BIGCS Imputation Server takes about 1 hour to complete the demo input VCF file, which contains 50 samples and 720k SNPs of chr1-22. It should be noted that BIGCS Imputation Server will delete the user's input VCF file once the task is completed, and only retain the result for 7 days.