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Streaming Long-Read Sequence Alignments for HLA Predictions Using HLAminer.

René L Warren1, Inanc Birol1,2

  • 1BC Cancer Genome Sciences Centre, Vancouver, BC, Canada.

Current Protocols
|March 27, 2025
PubMed
Summary
This summary is machine-generated.

This study introduces a streamlined protocol for predicting human leukocyte antigen (HLA) alleles from long-read sequencing data. The method efficiently analyzes complex genomic regions, even with lower coverage, improving immune gene analysis.

Keywords:
HLA inferences from sequencing dataHLA typinghuman leukocyte antigen (HLA)long‐read sequencing for HLA predictionnext‐generation sequencing‐based HLA analysis

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Area of Science:

  • Genomics
  • Immunogenetics
  • Bioinformatics

Background:

  • The human leukocyte antigen (HLA) gene cluster is crucial for immunity and highly polymorphic.
  • Analyzing HLA regions traditionally requires high-resolution data and complex methods.
  • Long-read sequencing offers potential for comprehensive HLA analysis.

Purpose of the Study:

  • To present a streamlined protocol for predicting HLA alleles from long-read sequencing data.
  • To demonstrate the efficiency and robustness of the HLAminer tool for HLA signature prediction.
  • To enable accessible HLA typing from whole-genome shotgun data.

Main Methods:

  • Directly streaming sequence alignments into HLAminer.
  • Utilizing long-read sequencing data from Oxford Nanopore Technologies (ONT) and Pacific Biosciences (PacBio).
  • Compatibility with any SAM file format-compatible read aligner, including minimap2.

Main Results:

  • The protocol successfully predicts HLA class I and class II alleles.
  • Robust HLA signature predictions were achieved even with older, lower-accuracy nanopore data.
  • Effective analysis was demonstrated with as low as 10× sequencing coverage.

Conclusions:

  • The presented method provides a simple, scalable, and efficient approach for HLA prediction from long-read sequencing data.
  • This protocol democratizes HLA typing by leveraging readily available whole-genome shotgun data.
  • The HLAminer tool facilitates accurate immune gene analysis across various sequencing datasets.