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MHConstructor: a high-throughput, haplotype-informed solution to the MHC assembly challenge.

Kristen J Wade1, Rayo Suseno1, Kerry Kizer1

  • 1Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA.

Genome Biology
|October 18, 2024
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Summary
This summary is machine-generated.

High genetic diversity in the human major histocompatibility complex (MHC) challenges DNA sequencing. MHConstructor offers a novel de novo assembly tool for accurate MHC analysis in large populations.

Keywords:
De novo assemblyHaplotypeHuman leukocyte antigen genesMajor histocompatibility complexShort-read sequencing

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Area of Science:

  • Genomics
  • Human Genetics
  • Bioinformatics

Background:

  • The human major histocompatibility complex (MHC) exhibits extreme genetic polymorphism.
  • Reference-based alignment methods are limited for MHC sequence assembly due to high variability.

Purpose of the Study:

  • To develop a novel bioinformatics pipeline for de novo assembly of the human MHC.
  • To enable high-throughput, reproducible MHC sequence analysis from short-read data.

Main Methods:

  • Incorporation of a short-read, de novo assembly algorithm into a specialized workflow.
  • Development of MHConstructor, a containerized pipeline for MHC assembly.
  • Application to both whole genome sequencing and target capture short-read data.

Main Results:

  • MHConstructor provides a self-contained tool for de novo MHC assembly from short-read data.
  • The pipeline supports high-throughput and reproducible analysis in population cohorts.
  • Enables alignment-free MHC sequence analysis.

Conclusions:

  • MHConstructor overcomes limitations of reference-based methods for MHC assembly.
  • Facilitates wider access to high-quality MHC sequence data.
  • Crucial for population genetics and personalized medicine research.