Phasing Classical HLA Alleles
3
0
Entering edit mode
16 months ago
jacob • 0

Hello,

I am trying to calculate "Type 1 Diabetes Genetic Risk Score 2" for participants in the UK Biobank. This algorithm takes into account HLA-DR-DQ haplotypes haplotypes to determine risk via DQA1-DQB1 alleles, meaning that classical HLA alleles must be phased in order to compute the score. However, UK Biobank HLA imputation values are not phased and data for parent haplotypes is not available.

Would anyone be able to point me to a software that would be able to phase the classical HLA alleles based on genotypes (i.e. if DQA1^501, DQA1^301, DQB1^201, and DQB1^302 are all present, the haplotypes are likely DQA1^501-DQB1^201 and DQA1^301-DQB1^302)? If not, can anyone share methodology for this can be done using population frequencies for known haplotypes?

Thank you for your help,

Jacob

PS: I used ^ instead of asterisks because the asterisks would not appear and would instead set the font to italics.

Here is the reference for the risk score I wish to compute:

Sharp SA, Rich SS, Wood AR, Jones SE, Beaumont RN, Harrison JW, Schneider DA, Locke JM, Tyrrell J, Weedon MN, Hagopian WA, Oram RA. Development and Standardization of an Improved Type 1 Diabetes Genetic Risk Score for Use in Newborn Screening and Incident Diagnosis. Diabetes Care. 2019 Feb;42(2):200-207. doi: 10.2337/dc18-1785. PMID: 30655379; PMCID: PMC6341291.

Haplotype UKBiobank HLA Phasing • 929 views
ADD COMMENT
1
Entering edit mode
16 months ago
Ming Tommy Tang ★ 4.5k

This paper was just out Tutorial: a statistical genetics guide to identifying HLA alleles driving complex disease https://www.nature.com/articles/s41596-023-00853-4

Also, take a look at https://github.com/mourisl/T1K this works with raw sequencing data

ADD COMMENT
0
Entering edit mode
16 months ago

I have had success with HLA-HD as well as xHLA software for HLA typing of Illumina WGS data. HLA-HD took more effort to get to successfully run, as well as a lot more computation time than xHLA. Meanwhile, xHLA was pretty fast to run as well to figure out. Accuracy has been harder for me to assess outside of benchmarking papers of HLA typing bioinformatics, but there is literature that covers both of these tools and more.

ADD COMMENT
0
Entering edit mode
ADD COMMENT

Login before adding your answer.

Traffic: 1905 users visited in the last hour
Help About
FAQ
Access RSS
API
Stats

Use of this site constitutes acceptance of our User Agreement and Privacy Policy.

Powered by the version 2.3.6