Tonight I watched Steven Verbruggen from OHMX.bio Belgium speak about “HLA typing using targeted third-generation sequencing methods” as part of London Calling 2022. They explained that HLA or the human leukocyte antigen complex is about 3 Mb in chromosome six. It is divided into three clusters, and all genes are very diverse. I did not realize HLA diversity was so rich! Typing these genes is important for transplantation, autoimmune disorders, and adverse drug reactions. The typing methods start with sample collection, usually blood. DNA extraction is then followed typically by PCR. Short-read technologies are used yet have limitations. Third-generation sequencing approaches can be used along with target enrichment to provide phasing information. Verbruggen mentioned another approach is to use adaptive sampling. Cas9-mediated enrichment provided 30-40x enrichment and sequences of interest. Adaptive sampling provided 10-20x enrichment and full HLA region sequences. Verbruggen then explained that they used both approaches: Cas9-mediated enrichment and then adaptive sampling. The team concluded that both enrichment methods worked and could be cost-efficient approaches for HLA typing. This session made me think about how these two enrichment approaches can be used together to maximize sequencing of regions of interest. Also, the adaptive sampling approach seemed sufficient for most needs and requires simpler prep than the Cas9-mediated enrichment.
