Dataset Information

A Novel Approach to Interrogating the Effects of Chemical Warfare Agent Exposure Using Organ-on-a-Chip Technology and Multiomic Analysis

ABSTRACT: Organ-on-a-chip platforms are utilized in global bioanalytical and toxicological studies as a way to reduce materials and increase throughput as compared to in vivo based experiments. These platforms bridge the infrastructure and regulatory gaps between in vivo animal work and human systems, with models that exemplify active biological pathways. In conjunction with the advent of increased capabilities associated with next generation sequencing and mass spectrometry based ‘-omic’ technologies, organ-on-a-chip platforms provide an excellent opportunity to investigate the global changes at multiple biological levels, including the transcriptome, proteome and metabolome. When investigated concurrently, a complete profile of cellular and regulatory perturbations can be characterized following treatment with specific agonists. In this study, global effects were observed and analyzed following liver chip exposure to the chemical warfare agent, VX. Even though the primary mechanism of action of VX (i.e. acetylcholinesterase inhibition) is well characterized, recent in vivo studies suggest additional protein binding partners that are implicated in metabolism and cellular energetic pathways. Also, secondary toxicity associated with peripheral organ systems, especially in human tissues, is not well defined. Our results demonstrate the efficacy of utilizing an organ-on-a-chip platform as a surrogate system to traditional in vivo studies. This is realized by specifically indicating significant dysregulation of a number of cellular processes in response to VX exposure including but not limited to amino acid synthesis, drug metabolism, and energetics pathways.

INSTRUMENT(S): Orbitrap Eclipse

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Hepatocyte, Liver

SUBMITTER: Conor Jenkins

LAB HEAD: Conor C Jenkins

PROVIDER: PXD037722 | Pride | 2023-03-11

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	20210301.pdResult	Other
	EmulateVx_1d_12pt5_1_FAIMS_01112021.raw	Raw
	EmulateVx_1d_12pt5_2_FAIMS_01112021.raw	Raw
	EmulateVx_1d_12pt5_3_FAIMS_01112021.raw	Raw
	EmulateVx_1d_25_1_FAIMS_01112021.raw	Raw

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Publications

A novel approach to interrogating the effects of chemical warfare agent exposure using organ-on-a-chip technology and multiomic analysis.

Goralski Tyler D P TDP Jenkins Conor C CC Angelini Daniel J DJ Horsmon Jennifer R JR Dhummakupt Elizabeth S ES Rizzo Gabrielle M GM Simmons Brooke L BL Liem Alvin T AT Roth Pierce A PA Karavis Mark A MA Hill Jessica M JM Sekowski Jennifer W JW Glover Kyle P KP

PloS one 20230213 2

Organ-on-a-chip platforms are utilized in global bioanalytical and toxicological studies as a way to reduce materials and increase throughput as compared to in vivo based experiments. These platforms bridge the infrastructure and regulatory gaps between in vivo animal work and human systems, with models that exemplify active biological pathways. In conjunction with the advent of increased capabilities associated with next generation sequencing and mass spectrometry based '-omic' technologies, or ...[more]

PMID: 36780485

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Project description:The most widely-used method for detecting and measuring genome-wide protein-DNA interactions is chromatin immunoprecipitation on tiling microarrays, commonly known as ChIP-chip. Many tiling array platforms, amplification methods, and analysis algorithms exist for ChIP-chip, but a rigorous assessment of the relative performance of these factors has not been reported. In a multi-lab simulation of a ChIP-chip experiment, we conducted the first objective analysis of tiling array platforms and analysis algorithms. We designed a complex mixture of human genomic DNA with a "spike-in" comprised of nearly 100 human sequences at various concentrations. Eight independent groups hybridized these mixtures to four different tiling array platforms. The groups were blind to the composition of the spike-in mix, the range of concentrations covered, or how many sequences it contained. 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