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fsusieR

License

The fsusieR package implements the Sum of Single Functions (fSuSiE) method for fine-mapping molecular QTLs from spatially structured traits like DNA methylation and histone modifications. fSuSiE extends the Sum of Single Effects (SuSiE) framework using wavelet-based functional regression to capture spatial correlations in molecular traits along the genome.

System Requirements

Software Dependencies

  • R (≥ 3.5.0)
  • Required R packages: wavethresh (≥ 4.6.8), ashr (≥ 2.2-47), mixsqp (≥ 0.3-43), matrixStats (≥ 0.62.0), Rfast (≥ 2.0.5), smashr
  • Optional: susieR and mvsusieR for comparation with fSuSiE

Operating Systems

  • macOS 12.0+
  • Ubuntu 20.04+
  • Windows 10+

Hardware

No special hardware required. Standard desktop computer with 8GB RAM sufficient for typical analyses.

Installation

Install the latest version from GitHub (typical install time: < 1 minute):

# install.packages("remotes")
remotes::install_github("stephenslab/smashr")
remotes::install_github("stephenslab/fsusieR")

Demo

Here is a quick example with simulated methylation data.

Expected output: 3 credible sets identifying causal SNPs, effect plots showing methylation changes

Usage

Basic fine-mapping analysis:

# Y: n x p matrix of molecular traits (n samples, p locations)
# X: n x J matrix of genotypes (n samples, J SNPs)
# L: maximum number of causal SNPs (default = 10)

fit <- susiF(X, Y, L = 10)

# Extract key results
fit$cs        # Credible sets
fit$pip       # Posterior inclusion probabilities  
fit$effects   # Estimated SNP effects

For genome-wide analyses, process by genomic regions (e.g., TADs):

# Define genomic regions
regions <- define_regions(positions, window = 2e6)

# Run fSuSiE per region
results <- lapply(regions, function(r) {
  susiF(X[, r$snps], Y[, r$traits], L = 20)
})

See the package website for detailed tutorials and examples.

Citing this work

If you use fsusieR in your work, please cite:

Denault, W.R.P., Sun, H., Carbonetto, P., Li, A., De Jager, L.P., Bennett, D, The Alzheimer’s Disease Functional Genomics Consortium, Wang, G. & Stephens, M. (2025). fSuSiE enables fine-mapping of QTLs from genome-scale molecular profiles. bioRxiv DOI: 10.1101/2025.08.17.670732

License

This project is licensed under the BSD-3-Clause License - see the LICENSE file for details.

Support

Please post issues for questions or bug reports.