A spectral framework to map QTLs affecting joint differential networks of gene co-expression.

Studying the mechanisms underlying the genotype-phenotype association is crucial in genetics. Gene expression studies have deepened our understanding of the genotype  →  expression  →  phenotype mechanisms. However, traditional expression quantitative trait loci (eQTL) methods often overlook the cri...

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Main Authors: Jiaxin Hu, Jesse N Weber, Lauren E Fuess, Natalie C Steinel, Daniel I Bolnick, Miaoyan Wang
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-04-01
Series:PLoS Computational Biology
Online Access:https://doi.org/10.1371/journal.pcbi.1012953
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author Jiaxin Hu
Jesse N Weber
Lauren E Fuess
Natalie C Steinel
Daniel I Bolnick
Miaoyan Wang
author_facet Jiaxin Hu
Jesse N Weber
Lauren E Fuess
Natalie C Steinel
Daniel I Bolnick
Miaoyan Wang
author_sort Jiaxin Hu
collection DOAJ
description Studying the mechanisms underlying the genotype-phenotype association is crucial in genetics. Gene expression studies have deepened our understanding of the genotype  →  expression  →  phenotype mechanisms. However, traditional expression quantitative trait loci (eQTL) methods often overlook the critical role of gene co-expression networks in translating genotype into phenotype. This gap highlights the need for more powerful statistical methods to analyze genotype  →  network  →  phenotype mechanism. Here, we develop a network-based method, called spectral network quantitative trait loci analysis (snQTL), to map quantitative trait loci affecting gene co-expression networks. Our approach tests the association between genotypes and joint differential networks of gene co-expression via a tensor-based spectral statistics, thereby overcoming the ubiquitous multiple testing challenges in existing methods. We demonstrate the effectiveness of snQTL in the analysis of three-spined stickleback (Gasterosteus aculeatus) data. Compared to conventional methods, our method snQTL uncovers chromosomal regions affecting gene co-expression networks, including one strong candidate gene that would have been missed by traditional eQTL analyses. Our framework suggests the limitation of current approaches and offers a powerful network-based tool for functional loci discoveries.
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institution Kabale University
issn 1553-734X
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language English
publishDate 2025-04-01
publisher Public Library of Science (PLoS)
record_format Article
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spelling doaj-art-07e297762d314f608eb8973f0052e54e2025-08-20T03:52:04ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582025-04-01214e101295310.1371/journal.pcbi.1012953A spectral framework to map QTLs affecting joint differential networks of gene co-expression.Jiaxin HuJesse N WeberLauren E FuessNatalie C SteinelDaniel I BolnickMiaoyan WangStudying the mechanisms underlying the genotype-phenotype association is crucial in genetics. Gene expression studies have deepened our understanding of the genotype  →  expression  →  phenotype mechanisms. However, traditional expression quantitative trait loci (eQTL) methods often overlook the critical role of gene co-expression networks in translating genotype into phenotype. This gap highlights the need for more powerful statistical methods to analyze genotype  →  network  →  phenotype mechanism. Here, we develop a network-based method, called spectral network quantitative trait loci analysis (snQTL), to map quantitative trait loci affecting gene co-expression networks. Our approach tests the association between genotypes and joint differential networks of gene co-expression via a tensor-based spectral statistics, thereby overcoming the ubiquitous multiple testing challenges in existing methods. We demonstrate the effectiveness of snQTL in the analysis of three-spined stickleback (Gasterosteus aculeatus) data. Compared to conventional methods, our method snQTL uncovers chromosomal regions affecting gene co-expression networks, including one strong candidate gene that would have been missed by traditional eQTL analyses. Our framework suggests the limitation of current approaches and offers a powerful network-based tool for functional loci discoveries.https://doi.org/10.1371/journal.pcbi.1012953
spellingShingle Jiaxin Hu
Jesse N Weber
Lauren E Fuess
Natalie C Steinel
Daniel I Bolnick
Miaoyan Wang
A spectral framework to map QTLs affecting joint differential networks of gene co-expression.
PLoS Computational Biology
title A spectral framework to map QTLs affecting joint differential networks of gene co-expression.
title_full A spectral framework to map QTLs affecting joint differential networks of gene co-expression.
title_fullStr A spectral framework to map QTLs affecting joint differential networks of gene co-expression.
title_full_unstemmed A spectral framework to map QTLs affecting joint differential networks of gene co-expression.
title_short A spectral framework to map QTLs affecting joint differential networks of gene co-expression.
title_sort spectral framework to map qtls affecting joint differential networks of gene co expression
url https://doi.org/10.1371/journal.pcbi.1012953
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