Title

Graph Regularized Dual Lasso for Robust eQTL Mapping

Abstract

Motivation: As a promising tool for dissecting the genetic basis of complex traits, expression quantitative trait loci (eQTL) mapping has attracted increasing research interest. An important issue in eQTL mapping is how to effectively integrate networks representing interactions among genetic markers and genes. Recently, several Lasso-based methods have been proposed to leverage such network information. Despite their success, existing methods have three common limitations: (i) a preprocessing step is usually needed to cluster the networks; (ii) the incompleteness of the networks and the noise in them are not considered; (iii) other available information, such as location of genetic markers and pathway information are not integrated.

Results: To address the limitations of the existing methods, we propose Graph-regularized Dual Lasso (GDL), a robust approach for eQTL mapping. GDL integrates the correlation structures among genetic markers and traits simultaneously. It also takes into account the incompleteness of the networks and is robust to the noise. GDL utilizes graph-based regularizers to model the prior networks and does not require an explicit clustering step. Moreover, it enables further refinement of the partial and noisy networks. We further generalize GDL to incorporate the location of genetic makers and gene-pathway information. We perform extensive experimental evaluations using both simulated and real datasets. Experimental results demonstrate that the proposed methods can effectively integrate various available priori knowledge and significantly outperform the state-of-the-art eQTL mapping methods.

Meeting Name

22nd Annual International Conference on Intelligent Systems for Molecular Biology, ISMB (2014: Jul. 11-15, Boston)

Department(s)

Computer Science

Document Type

Article - Conference proceedings

Document Version

Citation

File Type

text

Language(s)

English

Rights

© 2014 International Society for Computational Biology (ISCB), All rights reserved.

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