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Hybrid-GWAS-Modeling

Comparative modeling of SNP selection and phenotype prediction using sparse linear models (L₀-regularization) and non-linear models (Random Forests) on the QTLMAS 2010 GWAS dataset.


Overview

This project investigates and compares sparse linear and non-linear modeling strategies to identify significant SNPs associated with a quantitative trait in GWAS data. The objective is to benchmark model sparsity, generalization, and biological interpretability in high-dimensional genomic data.

Objectives

  • Apply and evaluate L₀-regularized regression and Random Forest models for SNP selection and phenotype prediction.
  • Explore hybrid modeling workflows combining sparse feature selection with non-linear model ranking.
  • Analyze the biological relevance of selected SNPs and their mapped genes.

Methods

  • Dataset: QTLMAS 2010 GWAS dataset (3,226 individuals, 9,723 SNPs).
  • Approaches:
    • L₀-Regularization: Iterative Hard Thresholding (IHT), Greedy Forward Selection, L0Learn R package (via Python rpy2).
    • Random Forest: Hyperparameter tuning, importance filtering, cumulative feature selection.
  • Tools & Libraries: Python, R, L0Learn, Scikit-learn, Random Forest, Iterative Hard Thresholding, Pandas, Seaborn, Matplotlib.

Key Results

  • L₀-regularized models: Achieved >85% SNP selection stability, identified <80 SNPs, and reduced Test MSE to 0.77.
  • Random Forest: Overfitted on the dataset (Test R² ≈ 0.30), revealing the additive nature of the trait with few dominant SNPs.
  • Biological Findings: Key SNPs mapped to genes like PRKAB2, RHOA, and SPTBN1, linked to metabolic and neuronal pathways.

Contributors

This was a collaborative project by:

  • Sanyukta Chapagain (LinkedIn)
  • Divyansh Rana
  • Vinamrata Sharma
  • Pranay Bandaru
  • Virija Nandamudi

Acknowledgments

We would like to thank our mentors and peers for their guidance and support throughout this project.


License

This project is shared for academic and learning purposes.

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Comparative analysis of sparse and non-linear modeling for SNP selection in GWAS data (QTLMAS 2010)

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