Description
This interactive web-tool contains data supplementing our manuscript A transient protein folding response targets aggregation in the early phase of TDP-43-mediated disease.
The objective of this web-tool is to provide an interactive interface for researchers to investigate relative protein/transcript abundance
of a user-defined set of input genes/proteins across mouse and human brain tissues with TDP-43 pathology. If using the app,
please be aware that the data was extracted from the papers below, which you should cite.
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San Gil et al. 2024: San Gil, R., Pascovici, D., Venturato, J., Brown-Wright, H., Mehta, P., Madrid San Martin, L., ... Walker, A. K. A transient protein folding response targets aggregation in the early phase of TDP-43-mediated neurodegeneration. Nature Communications 15, 1508. 10.1038/s41467-024-45646-9
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Hasan et al. 2022: Hasan, R., Humphrey, J., Bettencourt, C., Newcombe, J., Consortium, N.A., Lashley, T., Fratta, P., and Raj, T. (2022).
Transcriptomic analysis of frontotemporal lobar degeneration with TDP-43 pathology reveals cellular alterations across
multiple brain regions. Acta Neuropathol 143, 383-401. 10.1007/s00401-021-02399-9
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Umoh et al 2018: Umoh, M.E., Dammer, E.B., Dai, J., Duong, D.M., Lah, J.J., Levey, A.I., Gearing, M., Glass, J.D., and Seyfried, N.T. (2018).
A proteomic network approach across the ALS-FTD disease spectrum resolves clinical phenotypes and genetic
vulnerability in human brain. EMBO Mol Med 10, 48-62. 10.15252/emmm.201708202
Usage
- Select the dataset of choice:
- Mouse (cortex proteomics from San Gil et al., 2024)
- Human (datasets from Hasan et al., 2022 and Umoh et al., 2018)
- Both (compare human and mouse)
- Upload the genes/proteins of interest in the IDs text box on the left using gene symbol
- Click through the tabs to examine the data available and visualise log fold change
- Download the log fold change and p-values using the “Download all matches” link on the bottom left
Credits
This shiny app was constructed by Dana Pascovici, Insight Stats, and is hosted by The University of Queensland's Research Computing Centre.
Disclaimer
To the maximum extent permitted by law, The University of Queensland (including its employees and consultants) excludes all liability
to any person for any consequences, including but not limited to all losses, damages, costs, expenses and any other compensation, arisi
ng directly or indirectly from using, or relying on, this website (in part or in whole) and any information or material contained in it
. By using this site you are agreeing to these terms and conditions.
Table of log fold change, significance values, and WGCNA module membership for each gene/protein of the user-defined set. Use the drop-down box to select the datasets of interest, mouse, human, or both (human and mouse). The data returned in this table can be exported using the “Download all matches” link in the bottom left corner.
Log fold change of user input genes/proteins across published datasets
Visualisation of the relative log fold change for each input ID across each of the datasets. Circle colour is red for increased compared to controls, blue for decreased compared to controls, and white for unchanged, within each comparison. “-“ indicates the protein/gene was not detected in the indicated dataset. If a protein/gene was not detected in any dataset, it will not appear. Circle size is dependent on the magnitude of log fold change, the larger the change the larger the circle size.
This plot is optimal for a relatively small number of proteins. You can change the dataset to be viewed at any time using the Dataset choice drop-down menu on the top left.
Interactive volcano plot of the selected dataset and comparison
Visualisation of log fold change and p-value for all data points (blue) and user-defined set (red) of the selected dataset and comparison of interest. Change the dataset choice (i.e., mouse or human) and the subset of interest (e.g. TDPMouse.1week) at any time to explore the different datasets. The plot is interactive, hover the cursor over any point to view the ID, log fold change, and p-value. Use the ‘+’ and ‘-‘ functions to zoom in and out of the plot, the home icon to reset the axes, and the camera icon to download the plot.
Upset plot of intersecting significantly altered gene/protein sets
Visualisation of the number of intersecting gene/proteins of a user-defined set that are significantly altered (increased and decreased combined) across datasets (top 30 interactions shown).
Change the datasets to be viewed at any time using the drop-down menu on the top left.
The PresenceSummary column in the downloaded spreadsheet reports which proteins are present across the datasets considered, where “1” is detected and “0” is not detected. Using this column the data can be subset to identify the protein/gene list for a given bar on the upset plot.
Direction of change: Up, down, or unchanged in datasets
These pie charts show the percentage of the user-defined genes/proteins that are increased (up), decreased (down) or unchanged in the datasets. Definitions for significantly altered genes/proteins fold change cut-offs are outlined in each publication.
The bar chart on the right shows the number genes/proteins present in the datasets for each comparison listed.
Change the datasets to be viewed at any time using the Dataset choice drop-down menu on the top left. When “both” is selected you will be able to view all 3 Umoh et al, 2018 comparisons and a select 3 San Gil et al 2023 comparisons (4 wk, 6 wk, and recovery).
WGCNA module membership of user-defined sets
Weight gene correlation network analysis (WGCNA) clusters proteins into groups (modules) based on correlated protein abundance profiles across samples. Gene ontology of modules can reveal enrichment of biological pathways in control and disease samples.
Usage – By selecting “mouse” or “human” options from the Dataset choice dropdown box, the user can identify which modules the user-defined ID set have membership to, the log fold change in each sample, and the number of proteins that belong to each module. This tab does not work for “both” human and mouse comparison. To interpret the results, see Summary of modules and gene ontology (GO) below.
Summary of modules and gene ontology (GO):
Mouse - Modules and GO San Gil et al
- Black “myelination”– late-disease increased proteins, up in recovery
- Blue “protein transport” module – pre-onset and sustained increased proteins, down in recovery
- Brown “metabolic processes”– increased proteins in early-disease mice, sustained in recovery
- Turquoise “loss of synaptic transmission”– decreased in early-disease rNLS mice, increased in recovery
- Magenta “protein folding”– transiently increased proteins in pre-onset and onset rNLS mice, decreased in recovery
- Green “ribosome” – increased in control and rNLS mice in late disease and dox-dependent recovery. Not disease specific
- Red “mitochondria” – increased in control and rNLS mice at pre-onset and onset. Not disease specific.
- Pink “cytoskeletal organisation” – increased in control and rNLS mice at pre-onset and in dox-dependent recovery. Not disease specific.
Human - Modules and GO featured in Umoh et al
- Turquoise “synapse” – decreased in FTDvsCon (-)
- Blue “RNA splicing” – increased in FTDvsCon (+)
- Brown “mitochondrion” – decreased in FTDvsCon (-)
- Green “Extracellular matrix” – Increased FTDvsCon(+)
- Red “response to biotic stimulus” – Increased in FTDvsCon. (+)
- Pink “neuron differentiation” – Decreased in FTDvsCon (-)
- Magenta “zinc ion binding” – Increased in FTDvsCon (+)
- Purple “ homeostatic process” – Increased in FTDvsCon (+)
- Cyan “microtubule” – Slight decrease in module proteins in ALSvsCon, ALS/FTDvsCon and FTDvsCon (-)
- – Grey “antigen binding” – Increased in ALSvsCon, ALS/FTDvsCon, and FTDvsCon (+)
(+) = module protein abundance positively correlates with TDP-43 pathology levels in frontal cortex of disease cases
(-) = module protein abundance negative correlates with TDP-43 pathology levels in frontal cortex of disease cases