SAIGE-QTL

SAIGE-QTL is an R package developed with Rcpp for scalable and accurate expression quantitative trait locus (eQTL) mapping in single-cell studies.

Key Features

The SAIGE-QTL method provides several advantages for single-cell eQTL analysis:

  • Complex data modeling: Handles repeated and complex data structures arising from multiple cells per individual and relatedness between individuals
  • Discrete count modeling: Specifically designed for discrete read count data typical in single-cell RNA sequencing
  • Scalability: Fast and scalable for large datasets - can analyze:
    • 20,000+ genes
    • Tens to hundreds of cell types
    • Millions of cells
    • Millions of genetic variants
  • Rare variant testing: Includes set-based tests for rare variation effects where single-variant tests are underpowered

Supported Input Formats

SAIGE-QTL accepts genotype files in multiple standard formats:

  • PLINK (bed, bim, fam)
  • BGEN
  • VCF
  • BCF
  • SAV

Quick Start

  1. Install SAIGE-QTL - Choose from multiple installation methods
  2. Review the workflow overview - Understand the analysis pipeline
  3. Run Step 1 - Fit the null Poisson mixed model
  4. Perform association tests - Execute cis-eQTL or genome-wide analyses

Important Note on Normalization

⚠️ Critical: Accounting for total read counts per cell is essential in single-cell eQTL mapping. Consider using:

  • SCTransform function from the Seurat R package, OR
  • Including log(total read counts) and percentage of mitochondrial read counts as an offset in the Step 1 null model

What’s New

**July 31, 2025:

  • Export extdata/ in the docker container so users do not need to download the git repo when using the docker image wzhou88/saigeqtl:latest on example data

Version 0.3.2 (July 28, 2025):

  • Added --offsetCol option for using log of total read counts per cell as an offset
  • Enhanced installation process using pixi
  • See Installation logs for complete bug fixes and updates

Citation

SAIGE-QTL

Preprint: https://www.medrxiv.org/content/10.1101/2024.05.15.24307317v1

License

SAIGE-QTL is distributed under an MIT license.

Support

For questions about SAIGE-QTL, please contact: wzhou@broadinstitute.org

For technical issues and bug reports, please use the GitHub repository issue tracker.