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Dose-Response Analysis of RNA-Seq Profiles in Archival Formalin-Fixed Paraffin-Embedded Samples.

Metadata Updated: November 12, 2020

se of archival resources has been limited to date by inconsistent methods for genomic profiling of degraded RNA from formalin-fixed paraffin-embedded (FFPE) samples. RNA-seq offers a novel way to address this problem. In this study we evaluated transcriptomic dose responses using RNA-seq in paired FFPE and frozen (FROZ) samples from two archival studies in mice, one recent (20 years old). Experimental treatments included di(2-ethylhexyl)phthalate (DEHP) and dichloroacetic acid (DCA) for the 20 year-old studies, respectively. Total RNA was ribodepleted and sequenced using the Illumina HiSeq platform. In the recent study, FFPE samples showed high concordance in total reads (98% vs FROZ), fold-change values of differentially expressed genes (DEGs) (R2 = 0.99), highly enriched target pathways (90% overlap with FROZ), and benchmark dose estimates for preselected target genes (-2% overall vs FROZ). In contrast, RNA-seq data from older FFPE samples had lower total reads (70% vs FROZ) and poor concordance in global DEGs and pathways. Despite a 99% loss of counts, dose responses were still evident for target genes in FFPE samples and positively correlated with paired FROZ samples. These findings highlight potential variability in the quality of RNA-seq data from FFPE samples. More recent FFPE samples were highly similar to FROZ samples in sequencing quality metrics, DEG profiles, and dose-response parameters, while further methods development is needed for older or lower-quality FFPE samples. This work should help broaden the use of archival resources in both chemical safety and translational science.

This dataset is associated with the following publication: Hester, S., V. Bhat, B. Chorley, G. Carswell, W. Jones, L. Wehmas, and C. Wood. Dose-Response Analysis of RNA-Seq Profiles in Archival Formalin-Fixed Paraffin-Embedded (FFPE) Samples.. TOXICOLOGICAL SCIENCES. Society of Toxicology, 154(2): 202-213, (2016).

Access & Use Information

Public: This dataset is intended for public access and use. License: See this page for license information.

Downloads & Resources

References

https://doi.org/10.1093/toxsci/kfw161

Dates

Metadata Created Date November 12, 2020
Metadata Updated Date November 12, 2020

Metadata Source

Harvested from EPA ScienceHub

Additional Metadata

Resource Type Dataset
Metadata Created Date November 12, 2020
Metadata Updated Date November 12, 2020
Publisher U.S. EPA Office of Research and Development (ORD)
Maintainer
Identifier https://doi.org/10.23719/1503172
Data Last Modified 2016-12-01
Public Access Level public
Bureau Code 020:00
Schema Version https://project-open-data.cio.gov/v1.1/schema
Data Dictionary https://pasteur.epa.gov/uploads/10.23719/1503172/documents/Hester%20et%20al%20FFPE%20-%20Manuscript_v9f%20clean%20for%20clearance.docx
Data Dictionary Type application/vnd.openxmlformats-officedocument.wordprocessingml.document
Harvest Object Id 1a130296-8417-4b1f-9306-413a0608a550
Harvest Source Id 04b59eaf-ae53-4066-93db-80f2ed0df446
Harvest Source Title EPA ScienceHub
License https://pasteur.epa.gov/license/sciencehub-license.html
Program Code 020:095
Publisher Hierarchy U.S. Government > U.S. Environmental Protection Agency > U.S. EPA Office of Research and Development (ORD)
Related Documents https://doi.org/10.1093/toxsci/kfw161
Source Datajson Identifier True
Source Hash 8fe5ac3fc211b65627f4d4f495922f26f377defd
Source Schema Version 1.1

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