The Annals of Applied Statistics

A penalized regression model for the joint estimation of eQTL associations and gene network structure

Micol Marchetti-Bowick, Yaoliang Yu, Wei Wu, and Eric P. Xing

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Abstract

In this work, we present a new approach for jointly performing eQTL mapping and gene network inference while encouraging a transfer of information between the two tasks. We address this problem by formulating it as a multiple-output regression task in which we aim to learn the regression coefficients while simultaneously estimating the conditional independence relationships among the set of response variables. The approach we develop uses structured sparsity penalties to encourage the sharing of information between the regression coefficients and the output network in a mutually beneficial way. Our model, inverse-covariance-fused lasso, is formulated as a biconvex optimization problem that we solve via alternating minimization. We derive new, efficient optimization routines to solve each convex sub-problem that are based on extensions of state-of-the-art methods. Experiments on both simulated data and a yeast eQTL dataset demonstrate that our approach outperforms a large number of existing methods on the recovery of the true sparse structure of both the eQTL associations and the gene network. We also apply our method to a human Alzheimer’s disease dataset and highlight some results that support previous discoveries about the disease.

Article information

Source
Ann. Appl. Stat., Volume 13, Number 1 (2019), 248-270.

Dates
Received: April 2017
Revised: May 2018
First available in Project Euclid: 10 April 2019

Permanent link to this document
https://projecteuclid.org/euclid.aoas/1554861648

Digital Object Identifier
doi:10.1214/18-AOAS1186

Mathematical Reviews number (MathSciNet)
MR3937428

Keywords
eQTL mapping gene network estimation structured sparsity multiple-output regression covariance selection

Citation

Marchetti-Bowick, Micol; Yu, Yaoliang; Wu, Wei; Xing, Eric P. A penalized regression model for the joint estimation of eQTL associations and gene network structure. Ann. Appl. Stat. 13 (2019), no. 1, 248--270. doi:10.1214/18-AOAS1186. https://projecteuclid.org/euclid.aoas/1554861648


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Supplemental materials

  • Supplement to “A penalized regression model for the joint estimation of eQTL associations and gene network structure.”. We provide a supplementary document [Marchetti-Bowick et al. (2019)] that contains additional details about the optimization algorithm and additional results for both the synthetic and real data experiments.