Systems toxicology of Atlantic cod

Interspecies differences in sensitivity to chemical exposures pose a great challenge in toxicological risk assessments. How an organism copes with chemicals is largely determined by the genes and proteins that collectively function to defend against, detoxify and eliminate chemical stressors. This integrative network includes receptors and transcription factors, biotransformation enzymes, transporters, antioxidants, and metal- and heat-responsive genes, and is collectively known as the chemical
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BERGEN PUBLICATION
Location: UiB
Duration: 14 days, injections at day 0 and day 7
Sampling dates: 29-30 March 2017
Compounds tested: Polycyclic aromatic hydrocarbons (PAHs)/ Per- and polyfluoroalkyl substances (PFAS)
No. of test groups: 10
No. of fish per group: 21-22
No. of dead fish:

Aim:
*To investigate biological responses in Atlantic cod ( Gadus morhua) after in vivo exposure to a mixture of PAHs and PFASs, either singly or combined, at low (1x) or high (20x) doses.
*PFAS concentrations were
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To map genome wide transcriptome responses in Atlantic cod PCLS treated with BaP and EE2. See Yadetie et al., 2018.

This study involves all data gathered from the Kollevåg study - studying environmental pollution at a capped waste disposal site in Kollevåg, Askøy.

Cod were caged in Kollevåg (Stations 1, 2 and 3 - from inner to outer parts) and at a reference location (Ref station) for a period of six weeks, from 2nd September 2016, to 17-18th October 2016.

Build the chemical defensome gene list for 5 fish: Zebrafish (Danio rerio), Atlantic cod (Gadus morhua), medaka (Oryzias latipes), Atlantic killifish (Fundulus heteroclitus) and stickleback (Gasterosteus aculeatus). Source code and relevant files can be found on GitHub: https://github.com/zhxiaokang/fishDefensome/tree/main/defensomeGenes

To study the defensome genes' expression in early developmental stages of zebrafish and stickleback. Souce code and relevant files can be found on GitHub: https://github.com/zhxiaokang/fishDefensome/tree/main/developmentalStages

Exposing zebrafish to benzo(a)pyrene (B(a)P) (gene counts from NCBI GEO: GSE64198, previously published by Fang, et al. 2015. Souce code and relevant files can be found on GitHub: https://github.com/zhxiaokang/fishDefensome/tree/main/exposureResponse

Results from lipidomics analyses performed in cod liver microsomes of cod exposed to PAH and PFAS mixtures.

Some results from proteomics analyses of cod liver exposed to PAH and PFAS

Concentration of the egg yolk precursor protein vitellogenin in cod plasma

Gene expression of cyp1a and acox1 measured by qPCR in liver of Atlantic cod exposed to PAHs and PFASs

Semi-quantitative determination of Cyp1a protein amount in cod liver, using the ELISA method.

Measurement of DNA fragmentation using the Comet Assay, in white blood cells of Atlantic cod exposed to PAHs and PFASs

Measurements of PAH metabolites in bile (1-OH-napthalene, 2-OH-naphthalene, 1-OH-phenanthrene, 1-OH-pyrene) and PFAS compounds in liver (PFOS, PFOA, PFNA, PFTrDa)
in Atlantic cod exposed to mixtures of PAHs and PFASs.

Includes physiological informations regarding the fish samples: Weight, length, gender, date sampled, comments regarding physical apperance, in addition to calculations of condition factor (K), hepatosomatic index (HSI) and gonadosomatic index (GSI).

Enzyme activity of the oxidative stress enzymes glutathione S-transferase (Gst) and catalase (Cat) measured in cod liver

RNA-seq data for In vivo 7 samples. Only 32 RNA samples from liver of male fish sequenced. Illumina poly(A)-RNA sequencing at UiB GCF, as in Yadetie et al., 2018.

Information about the fish from the Kollevåg study

Enzyme activity of glutathione-s-transferase (Gst) and catalase (Cat) in Kollevåg samples

Concentrations of steroid hormones E2 and T in female cod plasma from Kollevåg fish

Chemical analyses in Kollevåg includes sediment contaminant concentrations, concentrations of various contaminants in cod liver and concentrations of PAH metabolites in cod bile.

Western blot results for Kollevåg samples.

More information can be found on GitHub: https://github.com/zhxiaokang/fishDefensome/tree/main/developmentalStages/zebrafish

Source code and relevant files can be found on GitHub: https://github.com/zhxiaokang/fishDefensome/tree/main/developmentalStages/stickleback

There are four datasheets in the Excel file: 1. Gene pattern and the corresponding category (the gene list is then divided into the other three datasheets); 2. These gene names (patterns) can be directly followed by either a letter or a number; 3. These gene names (patterns) should be directly followed by a letter; 4. These gene names (patterns) should be directly followed by a number.

The reactions existing in the auto-generated draft model are shown in blue, and the manually filled gaps are shown in green. Comparing our draft model with the same subsystem from model iHepatocytes2322, the missing reactions are highlighted in pink. The pink dots indicate the parent toxicants.

gadMorTrinity can be found at: https://doi.org/10.6084/m9.figshare.13067354.v1

COBRA Matlab toolbox was used.

Data file containing protein ID and pre-processed proteomic data, in addition to protein groups (peptide counts etc) determined in cod liver of cod exposed to PAH and PFAS mixtures.

Results of lipid species (expressed in pmol) determined in cod liver microsomes exposed to PAH and PFAS

Concentrations of PFAS in liver and PAH metabolites in bile of cod exposed to mixtures of PAHs and PFASs

Tail intensities (%) measured by the Comet Assay as indication of DNA fragmentation in blood cells of Atlantic cod exposed to PAHs and PFASs

Measured in cod liver by the ELISA method, in Atlantic cod exposed to PAHs and PFASs

Mean normalized expression (MNE) levels of cyp1a and acox1 measured in liver of Atlantic Cod exposed to PAH and PFAS mixtures

Concentrations of the egg yolk precursor protein vitellogenin (Vtg) in cod plasma - 10 samples from each exposure group, IV1 experiment

Measured in liver of Atlantic cod exposed to PAHs and PFASs

Biometrics of IV1 fish exposed to PAH and PFAS

This is an auto-generated model with COBRA Matlab toolbox. This model was deposited in BioModels [1] and assigned the identifier MODEL2010090003.

[1] Malik-Sheriff et al. BioModels — 15 years of sharing computational models in life science. Nucleic Acids Research. 2020 Jan, 48(D1):D407–415

This is an auto-generated model with COBRA Matlab toolbox. This model was deposited in BioModels [1] and assigned the identifier MODEL2010090002.

[1] Malik-Sheriff et al. BioModels — 15 years of sharing computational models in life science. Nucleic Acids Research. 2020 Jan, 48(D1):D407–415

This is an auto-generated model with COBRA Matlab toolbox. This model was deposited in BioModels [1] and assigned the identifier MODEL2010090001.

[1] Malik-Sheriff et al. BioModels — 15 years of sharing computational models in life science. Nucleic Acids Research. 2020 Jan, 48(D1):D407–415

Supplementary Table1 and Table2 for manuscript "The chemical defensome of fish"