A kinase to cytokine explorer to identify molecular regulators and potential therapeutic opportunities

  1. Marina Chan
  2. Yuqi Kang
  3. Shannon Osborne
  4. Michael Zager
  5. Taranjit S Gujral  Is a corresponding author
  1. Human Biology Division, Fred Hutchinson Cancer Center, United States
  2. Data Visualization Core, Fred Hutchinson Cancer Center, United States
  3. Department of Pharmacology, University of Washington, United States
2 figures, 1 table and 5 additional files

Figures

Figure 1 with 1 supplement
Modeling lipopolysaccharide (LPS)-mediated changes in secreted factors in human macrophages.

(A) A schematic showing LPS-mediated activation of human macrophages. (B) A plot showing changes in the levels of 191 secreted factors in response to LPS stimulation. Significantly increased or …

Figure 1—figure supplement 1
Representative KiR models for OPN and CCL4 release.

(A) Plots showing leave-one-out cross validation (LOOCV) error using elastic net regularization fit for OPN (left) and CCL4 (right). The error bars represent cross-validation error plus 1 SD. The …

An illustration showing the steps for using KinCytE.

(A) KinCytE offers three sections for users to explore potential cytokine(s) or chemokine(s) inhibiting drugs (Identify Drugs), related kinases (Identify Kinase), and cytokine signaling network …

Tables

Key resources table
Reagent type (species) or resourceDesignationSource or referenceIdentifiersAdditional information
Biological sample
(Homo sapiens)
Human CD14+ monocytesBloodworks NorthwestCat # 4585-18
Chemical compound, drugKinase inhibitors used for KiR model screeningNational Center for Advancing Translational Science, NIHSee Supplementary file 2
Software, algorithmR 4.2.1Venables and Smith, 2003https://www.r-project.org/
Software, algorithmglmnetFriedman et al., 2021https://cran.r-project.org/web/packages/glmnet/index.html
Software, algorithmggrepelSlowikowski et al., 2018https://github.com/slowkow/ggrepel
Software, algorithmtidyverseWickham et al., 2019https://tidyverse.tidyverse.org/index.html
Software, algorithmggpubrKassambara, 2023https://rpkgs.datanovia.com/ggpubr/index.html
Software, algorithmggplot2Wickham, 2009http://ggplot2.org
Software, algorithmpheatmapKolde and Kolde, 2015https://cran.r-project.org/package=pheatmap
Software, algorithmPython 3.7.11Van Rossum and Drake, 2009https://www.python.org/downloads/release/python-3711/
Software, algorithmNumpyHarris et al., 2020https://numpy.org/
Software, algorithmPandasMcKinney, 2010https://pandas.pydata.org/
Software, algorithmScipyVirtanen et al., 2020https://scipy.org/
Software, algorithmSeabornWaskom, 2021https://seaborn.pydata.org/
Software, algorithmMatplotlibHunter, 2007https://matplotlib.org/

Additional files

MDAR checklist
https://cdn.elifesciences.org/articles/91472/elife-91472-mdarchecklist1-v1.docx
Supplementary file 1

Fold change of average cytokine level in LPS-treated macrophage compared to control.

https://cdn.elifesciences.org/articles/91472/elife-91472-supp1-v1.xlsx
Supplementary file 2

Percentage changes in cytokine level in kinase inhibitor-treated macrophages compared to control.

https://cdn.elifesciences.org/articles/91472/elife-91472-supp2-v1.xlsx
Supplementary file 3

Summary table of predicted kinases involved in cytokine models.

https://cdn.elifesciences.org/articles/91472/elife-91472-supp3-v1.zip
Supplementary file 4

Predicted cytokine levels in macrophares treated with kinase inhibitors.

https://cdn.elifesciences.org/articles/91472/elife-91472-supp4-v1.zip

Download links