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Gene set enrichment analysis of microarray data from Pimephales promelas (Rafinesque), a non-mammalian model organism.

ABSTRACT: Methods for gene-class testing, such as Gene Set Enrichment Analysis (GSEA), incorporate biological knowledge into the analysis and interpretation of microarray data by comparing gene expression patterns to pathways, systems and emergent phenotypes. However, to use GSEA to its full capability with non-mammalian model organisms, a microarray platform must be annotated with human gene symbols. Doing so enables the ability to relate a model organism's gene expression, in response to a given treatment, to potential human health consequences of that treatment. We enhanced the annotation of a microarray platform from a non-mammalian model organism, and then used the GSEA approach in a reanalysis of a study examining the biological significance of acute and chronic methylmercury exposure on liver tissue of fathead minnow (Pimephales promelas). Using GSEA, we tested the hypothesis that fathead livers, in response to methylmercury exposure, would exhibit gene expression patterns similar to diseased human livers.We describe an enhanced annotation of the fathead minnow microarray platform with human gene symbols. This resource is now compatible with the GSEA approach for gene-class testing. We confirmed that GSEA, using this enhanced microarray platform, is able to recover results consistent with a previous analysis of fathead minnow exposure to methylmercury using standard analytical approaches. Using GSEA to compare fathead gene expression profiles to human phenotypes, we also found that fathead methylmercury-treated livers exhibited expression profiles that are homologous to human systems & pathways and results in damage that is similar to those of human liver damage associated with hepatocellular carcinoma and hepatitis B.This study describes a powerful resource for enabling the use of non-mammalian model organisms in the study of human health significance. Results of microarray gene expression studies involving fathead minnow, typically used for aquatic ecological toxicology studies, can now be used to generate hypotheses regarding consequences of contaminants and other stressors on humans. The same approach can be used with other model organisms with microarray platforms annotated in a similar manner.

SUBMITTER: Thomas MA

PROVIDER: S-EPMC3037904 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Gene set enrichment analysis of microarray data from Pimephales promelas (Rafinesque), a non-mammalian model organism.

Thomas Michael A MA Yang Luobin L Carter Barbara J BJ Klaper Rebecca D RD

BMC genomics 20110126

<h4>Background</h4>Methods for gene-class testing, such as Gene Set Enrichment Analysis (GSEA), incorporate biological knowledge into the analysis and interpretation of microarray data by comparing gene expression patterns to pathways, systems and emergent phenotypes. However, to use GSEA to its full capability with non-mammalian model organisms, a microarray platform must be annotated with human gene symbols. Doing so enables the ability to relate a model organism's gene expression, in response ...[more]

PMID: 21269471

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Project description:Mosquitoes function as important vectors for many diseases globally and can have substantial negative economic, environmental, and health impacts. Specifically, West Nile virus (WNv) is a significant and increasing threat to wildlife populations and human health throughout North America. Mosquito control is an important means of controlling the spread of WNv, as the virus is primarily spread between avian and mosquito vectors. This is of particular concern for avian host species such as the Greater sage-grouse (Centrocercus urophasianus), in which WNv negatively impacts fitness parameters. Most mosquito control methods focus on the larval stages. In North America, control efforts are largely limited to larvicides, which require repeated application and have potentially negative ecological impacts. There are multiple potential advantages to using indigenous fish species as an alternative for larval control including lowered environmental impact, decreased costs in terms of time and financial inputs, and the potential for the establishment of self-sustaining fish populations. We tested the efficacy of using fathead minnows (Pimephales promelas) as biological control for mosquito populations in livestock reservoirs of semiarid rangelands. We introduced minnows into 10 treatment reservoirs and monitored an additional 6 non-treated reservoirs as controls over 3 years. Adult mosquitoes of species known to transmit WNv (e.g., Culex tarsalis) were captured at each site and mosquito larvae were also present at all sites. Stable isotope analysis confirmed that introduced fathead minnows were feeding at the mosquito larvae trophic level in all but one treatment pond. Treatment ponds demonstrated suppressed levels of mosquito larva over each season compared to controls with a model-predicted 114% decrease in larva density within treatment ponds. Minnows established self-sustaining populations throughout the study in all reservoirs that maintained sufficient water levels. Minnow survival was not influenced by water quality. Though minnows did not completely eradicate mosquito larvae, minnows are a promising alternative to controlling mosquito larvae density within reservoirs. We caution that careful site selection is critical to avoid potential negative impacts, but suggest the introduction of fathead minnows in reservoirs can dramatically reduce mosquito larva abundance and potentially help mitigate vector-borne disease transmission.

Project description:Omics approaches are broadly used to explore endocrine and toxicity-related pathways and functions. Nevertheless, there is still a significant gap in knowledge in terms of understanding the endocrine system and its numerous connections and intricate feedback loops, especially in non-model organisms. The fathead minnow (Pimephales promelas) is a widely used small fish model for aquatic toxicology and regulatory testing, particularly in North America. A draft genome has been published, but the amount of available genomic or transcriptomic information is still far behind that of other more broadly studied species, such as the zebrafish. Here, we used a proteogenomics approach to survey the tissue-specific proteome and transcriptome profiles in adult male fathead minnow. To do so, we generated a draft transcriptome using short and long sequencing reads from liver, testis, brain, heart, gill, head kidney, trunk kidney, and gastrointestinal tract. We identified 30,378 different putative transcripts overall, with the assembled contigs ranging in size from 264 to over 9,720 nts. Over 17,000 transcripts were >1,000 nts, suggesting a robust transcriptome that can be used to interpret RNA sequencing data in the future. We also performed RNA sequencing and proteomics analysis on four tissues, including the telencephalon, hypothalamus, liver, and gastrointestinal tract of male fish. Transcripts ranged from 0 to 600,000 copies per gene and a large portion were expressed in a tissue-specific manner. Specifically, the telencephalon and hypothalamus shared the most expressed genes, while the gastrointestinal tract and the liver were quite distinct. Using protein profiling techniques, we identified a total of 4,045 proteins in the four tissues investigated, and their tissue-specific expression pattern correlated with the transcripts at the pathway level. Similarly to the findings with the transcriptomic data, the hypothalamus and telencephalon had the highest degree of similarity in the proteins detected. The main purpose of this analysis was to generate tissue-specific omics data in order to support future aquatic ecotoxicogenomic and endocrine-related studies as well as to improve our understanding of the fathead minnow as an ecological model.

Dataset Information

Gene set enrichment analysis of microarray data from Pimephales promelas (Rafinesque), a non-mammalian model organism.

Publications

Gene set enrichment analysis of microarray data from Pimephales promelas (Rafinesque), a non-mammalian model organism.

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