18 research outputs found

    GEORAC: an RNA-seq Atlas Constructor for the Gene Expression Omnibus

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    The meteoric rise of next-generation sequencing technologies over the past 15 years has resulted in a voluminous amount of data generated by modern biological and clinical studies. RNA sequencing, colloquially referred to as RNA-Seq, is a next-generation approach capable of surveying and quantifying whole organism transcriptomes. RNA-Seq methods are valued over microarray assays for their ability to avoid cross-hybridization signal noise, to quantify gene or transcript expression without assay-specific upper limits, to natively provide single-nucleotide genomic resolution, and to allow for de novo transcriptome assemblies. Many thousands of RNA-Seq studies have been published over the past seven years, and a significant area of bioinformatics research has focused on the creation of atlases that aggregate RNA-Seq results. These atlases are crucially useful for surveying trends in gene expression across published studies, for inspecting potentially contentious claims made by novel or prior work, and for synthesizing future research directions. The Expression Atlas currently serves as the canonical example for an RNA-Seq atlas and presents results from over 3,000 studies across numerous model research organisms. An issue with the Expression Atlas is that it forcibly applies a uniform secondary re-analysis pipeline to each RNA-Seq study incorporated within its database; this approach presents a conceptual challenge to studies whose results have been generated and published using established, well-tested workflows. Thus, there exists a critical need to provide for construction of RNA-Seq atlases that precisely reflect original results presented within the literature, and the primary objective of this dissertation is to provide a workflow that allows for transparent, reproducible construction of RNA-Seq atlases from study meta- and expression data housed within the National Center for Biomedical Information’s Gene Expression Omnibus (GEO). The challenge of this goal is exacerbated by the highly flexible design of GEO, which allows researchers to define novel metadata attributes and values at will and to submit expression results in virtually any format. Following an introductory background into modern genomics and RNA-Seq, the second chapter of this work presents GEOMP, a metadata parser and relational database constructor for the Gene Expression Omnibus. The subsequent third chapter describes GEOMP2, an in-place augmentation of GEOMP that provides further atomization and loading of sample-specific characteristics tags; this chapter significantly presents results from a pilot study surveying bioinformatics methods reproducibility across the zebrafish, mouse, and human research communities using metadata parsed and output by GEOMP2. Chapter four details GEORGET, a pipeline designed to rehabilitate, translate, and load expression data pulled from GEO into the relational database store constructed by GEOMP2. Chapter five concludes with discussion of future directions needed to expand and improve upon the current GEORAC workflow and the associated methods reproducibility study

    Transcriptome signatures of wastewater effluent exposure in larval zebrafish vary with seasonal mixture composition in an effluent-dominated stream

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    Wastewater treatment plant (WWTP) effluent-dominated streams provide critical habitat for aquatic and terrestrial organisms but also continually expose them to complex mixtures of pharmaceuticals that can potentially impair growth, behavior, and reproduction. Currently, few biomarkers are available that relate to pharmaceutical-specific mechanisms of action. In the experiment reported in this paper, zebrafish (Danio rerio) embryos at two developmental stages were exposed to water samples from three sampling sites (0.1 km upstream of the outfall, at the effluent outfall, and 0.1 km below the outfall) during base-flow conditions from two months (January and May) of a temperate-region effluent-dominated stream containing a complex mixture of pharmaceuticals and other contaminants of emerging concern. RNA-sequencing identified potential biological impacts and biomarkers of WWTP effluent exposure that extend past traditional markers of endocrine disruption. Transcriptomics revealed changes to a wide range of biological functions and pathways including cardiac, neurological, visual, metabolic, and signaling pathways. These transcriptomic changes varied by developmental stage and displayed sensitivity to variable chemical composition and concentration of effluent, thus indicating a need for stage-specific biomarkers. Some transcripts are known to be associated with genes related to pharmaceuticals that were present in the collected samples. Although traditional biomarkers of endocrine disruption were not enriched in either month, a high estrogenicity signal was detected upstream in May and implicates the presence of unidentified chemical inputs not captured by the targeted chemical analysis. This work reveals associations between bioeffects of exposure, stage of development, and the composition of chemical mixtures in effluent-dominated surface water. The work underscores the importance of measuring effects beyond the endocrine system when assessing the impact of bioactive chemicals in WWTP effluent and identifies a need for non-targeted chemical analysis when bioeffects are not explained by the targeted analysis

    Oak Park Energy Efficiency & Carbon Reduction (Semester Unknown) IPRO 329: OakParkEnergyEfficiencyAndCarbonReductionIPRO329ProjectPlantF10_redacted

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    The overall purpose of the IPRO 329 team is to work with the Village of Oak Park in order to implement a strategic plan to educate Oak Park residents in making their homes more efficient and work toward a community wide reduction of energy and water usage. In doing so, we also hope to gain valuable experience in working in a team with members with varying degrees of experience and skills.Sponsorship: Oak ParkDeliverable

    Oak Park Energy Efficiency & Carbon Reduction (Semester Unknown) IPRO 329: OakParkEnergyEfficiencyAndCarbonReductionIPRO329BrochureF10

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    The overall purpose of the IPRO 329 team is to work with the Village of Oak Park in order to implement a strategic plan to educate Oak Park residents in making their homes more efficient and work toward a community wide reduction of energy and water usage. In doing so, we also hope to gain valuable experience in working in a team with members with varying degrees of experience and skills.Sponsorship: Oak ParkDeliverable

    Oak Park Energy Efficiency & Carbon Reduction (Semester Unknown) IPRO 329

    No full text
    The overall purpose of the IPRO 329 team is to work with the Village of Oak Park in order to implement a strategic plan to educate Oak Park residents in making their homes more efficient and work toward a community wide reduction of energy and water usage. In doing so, we also hope to gain valuable experience in working in a team with members with varying degrees of experience and skills.Sponsorship: Oak ParkDeliverable

    Oak Park Energy Efficiency & Carbon Reduction (Semester Unknown) IPRO 329: OakParkEnergyEfficiencyAndCarbonReductionIPRO329FinalReportF10

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    The overall purpose of the IPRO 329 team is to work with the Village of Oak Park in order to implement a strategic plan to educate Oak Park residents in making their homes more efficient and work toward a community wide reduction of energy and water usage. In doing so, we also hope to gain valuable experience in working in a team with members with varying degrees of experience and skills.Sponsorship: Oak ParkDeliverable

    Oak Park Energy Efficiency & Carbon Reduction (Semester Unknown) IPRO 329: OakParkEnergyEfficiencyAndCarbonReductionIPRO329MidTermPresentationF10

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    The overall purpose of the IPRO 329 team is to work with the Village of Oak Park in order to implement a strategic plan to educate Oak Park residents in making their homes more efficient and work toward a community wide reduction of energy and water usage. In doing so, we also hope to gain valuable experience in working in a team with members with varying degrees of experience and skills.Sponsorship: Oak ParkDeliverable

    Oak Park Energy Efficiency & Carbon Reduction (Semester Unknown) IPRO 329: OakParkEnergyEfficiencyAndCarbonReductionIPRO329PosterF10

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    The overall purpose of the IPRO 329 team is to work with the Village of Oak Park in order to implement a strategic plan to educate Oak Park residents in making their homes more efficient and work toward a community wide reduction of energy and water usage. In doing so, we also hope to gain valuable experience in working in a team with members with varying degrees of experience and skills.Sponsorship: Oak ParkDeliverable
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