Lead Modulates trans- and cis-Expression Quantitative Trait Loci (eQTLs) in Drosophila melanogaster Heads

Wen, Qian; Gurdziel, Katherine; Piqué-Regi, Roger; Ruden, Douglas M.

doi:10.3389/fgene.2018.00395

Cited by 14 publications

(13 citation statements)

References 58 publications

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“…Last year, in 2020, the Associate Editors, Editorial Managers, and I decided to start a new Frontiers Media journal, Frontiers in Toxicology, to expand the type of toxicology articles that are submitted. Currently, my laboratory, while still focused on toxicology studies, moved from toxicogenomics analyses to more transcriptomic level and epigenomics analyses ( Senut et al, 2012 ; Senut et al, 2014 ; Sen et al, 2015a ; Sen et al, 2015b ; Sen et al, 2015c ; Qu et al, 2017a ; Qu et al, 2017b ; Ruden et al, 2017 ; Sen et al, 2017 ; Qu et al, 2018 ; Shah et al, 2019 ; Shah et al, 2020 ). In this article, I give a short overview of past discoveries, current challenges, and future perspectives for the revitalization of the Frontiers in Toxicogenomics journal.…”

Section: Introductionmentioning

confidence: 99%

10 Years of Toxicogenomics section in Frontiers in Genetics: Past discoveries and Future Perspectives

Ruden

2022

Front. Genet.

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The Frontiers Media family has over 200 journals, which are each headed by usually one Field Chief Editor, and several thousand specialty sections, which are each headed by one or more Specialty Chief Editors. The year 2021 was the 10th anniversary of the founding of the Frontiers in Genetics journal and the Frontiers in Toxicogenomics specialty section of this journal. In 2021, we also announce one of the newest of the Frontiers journals–Frontiers in Toxicology which is part of the Frontiers Media family of journals but independent of Frontiers in Genetics. Dr. Ruden is the founding, and currently sole, Specialty Chief Editor of Frontiers in Toxicogenomics and one of 9 Specialty Chief Editors of Frontiers in Toxicology. The new Field Chief editor of Frontiers in Toxicology will be Dr. Bengt Fadeel of the Karolinska Institute in Sweden. As of 2021, Frontiers in Toxicogenomics has published over 138 articles and has over 370 Editors including 90 Associate Editors and 280 Review Editors. The Frontiers in Genetics impact factor was initially approximately 2.5 when it was first listed in PubMed in 2015 and has risen steadily to its current value of 4.8, which is typical for the majority of the over 200 Frontiers journals that have established impact factors. In this overview of the first decade of Frontiers in Toxicogenomics, we discuss the top 5 articles with the highest Scopus citations, which were all written in the first few years of the journal. The article with the highest number of citations, with 353 Scopus over 600 Google Scholar citations, and the highest average number of citations (67) that steadily increased from 10 citations in 2013 to 119 citations in 2021, was written in 2012 by Dr. Ruden’s laboratory and titled, “Using Drosophila melanogaster as a model for genotoxic chemical mutational studies with a new program, SnpSift.” The five most influential authors who published in the journal in the past 10 years based on Scopus citations of a particular paper are Dr. Ruden’s laboratory, with 353 Scopus citations for the SnpSift paper mentioned above; Drs. Brock Christensen and Carmen J. Marsit, with 86 Scopus citations for their review, “Epigenomics in environmental health”; Dr. Michael Aschner and colleagues, with 61 Scopus citations for their paper “Genetic factors and manganese-induced neurotoxicity”; and Dr. Sandra C. dos Santos and colleagues, with 59 Scopus citations for their paper, “Yeast toxicogenomics: genome-wide responses to chemical stresses with impact in environmental health, pharmacology, and biotechnology.” While the top 5 papers were published in the early years of the journal, we will also discuss a more recent article published in 2018 on a comparison of RNA-seq and microarray methods by Dr. Michael Liguori’s laboratory, “Comparison of RNA-Seq and Microarray Gene Expression Platforms for the Toxicogenomic Evaluation of Liver From Short-Term Rat Toxicity Studies,” that far exceeds the number of downloads and views of all the other articles published in the first 10 years of the journal and will likely be a top cited paper in the second decade highlights of this journal. Finally, we discuss where the Frontiers in Toxicogenomics specialty journal and the Frontiers in Toxicology journal will go to advance the field of toxicogenomics, and more generally, toxicology, in the future.

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Section: Introductionmentioning

confidence: 99%

10 Years of Toxicogenomics section in Frontiers in Genetics: Past discoveries and Future Perspectives

Ruden

2022

Front. Genet.

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“…Power to detect eQTL with modest effects is directly related to the number of strains in which the trait is measured ( Ruden et al 2009 ; King, Macdonald et al . 2012 ; Qu et al 2018 ; Arvanitis et al 2022 ). By using 93–96 strains in our eQTL analyses, lack of power to detect modest-effect eQTL likely contributes to our estimates of tissue-specificity.…”

Section: Discussionmentioning

confidence: 99%

“…Transcriptomics studies have repeatedly demonstrated that exposure to heavy metal stressors increases expression of several gene families involved in metal detoxification, metabolism, and transport as well as oxidative stress response ( González et al 2008 ; Catalán et al 2016 ; Calap-Quintana et al 2017 ; Qu et al 2018 ; Everman et al 2021 ; Felmlee et al 2022 ; Green et al 2022 ). However, the gene expression response to metal stress is itself also subject to genetic variation in the regulation of the transcriptional response, i.e.…”

Section: Introductionmentioning

confidence: 99%

Gene expression variation underlying tissue-specific responses to copper stress in Drosophila melanogaster

Everman,

Macdonald

2024

G3: Genes, Genomes, Genetics

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Copper is one of a handful of biologically necessary heavy metals that is also a common environmental pollutant. Under normal conditions, copper ions are required for many key physiological processes. However, in excess, copper results in cell and tissue damage ranging in severity from temporary injury to permanent neurological damage. Because of its biological relevance, and because many conserved copper-responsive genes respond to non-essential heavy metal pollutants, copper resistance in Drosophila melanogaster is a useful model system with which to investigate the genetic control of the heavy metal stress response. Because heavy metal toxicity has the potential to differently impact specific tissues, we genetically characterized the control of the gene expression response to copper stress in a tissue-specific manner in this study. We assessed the copper stress response in head and gut tissue of 96 inbred strains from the Drosophila Synthetic Population Resource (DSPR) using a combination of differential expression analysis and expression quantitative trait locus (eQTL) mapping. Differential expression analysis revealed clear patterns of tissue-specific expression. Tissue and treatment specific responses to copper stress were also detected using eQTL mapping. eQTL associated with MtnA, Mdr49, Mdr50, and Sod3 exhibited both genotype-by-tissue and genotype-by-treatment effects on gene expression under copper stress, illuminating tissue- and treatment-specific patterns of gene expression control. Together, our data build a nuanced description of the roles and interactions between allelic and expression variation in copper-responsive genes, provide valuable insight into the genomic architecture of susceptibility to metal toxicity, and highlight candidate genes for future functional characterization.

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“…In this study, we therefore explored the effect of genetic variation on gene expression and organismal phenotypes in the context of in vivo enteric infection in the DGRP. Despite several valuable eQTL studies in Drosophila involving the DGRP [33][34][35][36][37] and the Drosophila Synthetic Population Resource (DSPR) [38][39][40], none have so far focused on the response to infection.…”

Section: Introductionmentioning

confidence: 99%

cis-regulatory variation modulates susceptibility to enteric infection in the Drosophila genetic reference panel

et al. 2020

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Background: Resistance to enteric pathogens is a complex trait at the crossroads of multiple biological processes. We have previously shown in the Drosophila Genetic Reference Panel (DGRP) that resistance to infection is highly heritable, but our understanding of how the effects of genetic variants affect different molecular mechanisms to determine gut immunocompetence is still limited. Results: To address this, we perform a systems genetics analysis of the gut transcriptomes from 38 DGRP lines that were orally infected with Pseudomonas entomophila. We identify a large number of condition-specific, expression quantitative trait loci (local-eQTLs) with infection-specific ones located in regions enriched for FOX transcription factor motifs. By assessing the allelic imbalance in the transcriptomes of 19 F1 hybrid lines from a large round robin design, we independently attribute a robust cis-regulatory effect to only 10% of these detected local-eQTLs. However, additional analyses indicate that many local-eQTLs may act in trans instead. Comparison of the transcriptomes of DGRP lines that were either susceptible or resistant to Pseudomonas entomophila infection reveals nutcracker as the only differentially expressed gene. Interestingly, we find that nutcracker is linked to infection-specific eQTLs that correlate with its expression level and to enteric infection susceptibility. Further regulatory analysis reveals one particular eQTL that significantly decreases the binding affinity for the repressor Broad, driving differential allele-specific nutcracker expression. Conclusions: Our collective findings point to a large number of infection-specific cis-and transacting eQTLs in the DGRP, including one common non-coding variant that lowers enteric infection susceptibility.

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Lead Modulates trans- and cis-Expression Quantitative Trait Loci (eQTLs) in Drosophila melanogaster Heads

Cited by 14 publications

References 58 publications

10 Years of Toxicogenomics section in Frontiers in Genetics: Past discoveries and Future Perspectives

10 Years of Toxicogenomics section in Frontiers in Genetics: Past discoveries and Future Perspectives

Gene expression variation underlying tissue-specific responses to copper stress in Drosophila melanogaster

cis-regulatory variation modulates susceptibility to enteric infection in the Drosophila genetic reference panel

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