CLLCytokineScreen2021 Home Page

Welcome to the CLLCytokineScreen2021 wiki!

In this repository, we present the complete analysis and associated datasets of the Drug-Cytokine Combinatorial Screen project and source code for the paper. The repository contains everything required to reproduce the seven figures of the paper:

Combinatorial drug-microenvironment interaction mapping reveals cell-extrinsic drug resistance mechanisms and clinically relevant patient subgroups in CLL

Peter-Martin Bruch*, Holly A. R. Giles*, Carolin Kolb, Sophie A. Herbst, Tina Becirovic, Tobias Roider, Junyan Lu, Sebastian Scheinost, Lena Wagner, Jennifer Huellein, Ivan Berest, Mark Kriegsmann, Katharina Kriegsmann, Christiane Zgorzelski, Peter Dreger, Judith B. Zaugg, Carsten Müller-Tidow, Thorsten Zenz, Wolfgang Huber*, Sascha Dietrich*

*These authors contributed equally to this work.

The data can be accessed in .RData format in /data and in .txt format in inst/extdata. The scripts can be found in vignettes/src and the associated html files (showing the analysis in full) in inst/doc. To run the entire analysis, clone the repository and run the script CLLCytokineScreen2021.Rmd. Make sure you have updated R to at least version 4.1.0 and have installed all libraries in CLLCytokineScreen2021.Rmd beforehand.

If you use this analysis in published research, please cite the paper. Please refer to the manuscript for more details on experimental methods and analysis.

The presented analysis was performed by Holly Giles and Peter-Martin Bruch, building on scripts from Sascha Dietrich, Wolfgang Huber, Junyan Lu, Malgorzata Oles, Frederik Ziebell, Sophie Herbst and Ivan Berest. This repository is maintained by Holly Giles. If you have questions, email me at holly.giles@embl.de.

The data can also be explored interactively via the online shiny app.

Further details on the contents of this repository:

Folder	Contains
R	themes_colors.R : all themes and colour schemes used in figures
data	Heatmap_clusters.RData: tibble with patient IDs and their assigned cluster
	IbrSTAT6iComb.RData: tibble containing viability data for samples treated with Ibrutinib + IL4 + STAT6 inhibitor
	LDT.RData: tibble containing lymphocyte doubling times for selected patients
	cytReceptors.RData: tibble containing EnsemblIDs for receptors of stimuli used in screen
	cyt_and_receptors.RData: tibble containing all stimuli and their associated receptors, plus KEGG and EnsemblIDs
	cytokines.RData: tibble containing meta data on all stimuli in screen
	dds_smp.RData: DeseqDataset containing RNA count data, and associated meta data for selected patient samples from screen
	dds_smp_full.RData: Larger DeseqDataset containing RNA count data, and associated meta data for all available patient samples
	df.RData : tibble containing viability data from Combinatorial Screen
	diffTF_large.RData: tibble containing diffTF weighted mean difference values for 636 TFs, calculated using 9 trisomy 12 versus 43 non-trisomy 12 CLL ATACseq samples
	diffTF_small.RData: tibble containing diffTF weighted mean difference values for 636 TFs, calculated using 2 trisomy 12 versus 2 non-trisomy 12 CLL ATACseq samples
	diffTF_ibet.RData: tibble containing diffTF weighted mean difference values, calculated using 4 control versus 4 IBET-762 treated CLL ATACseq samples
	drugs.RData: tibble containing meta data on all drugs in screen
	ihc_patient_data.RData: 596 x 7 tibble containing IHC staining intensities forpIRAK4, pSTAT6 and STAT6 staining in CLL and healthy tissue
	ihc_surv_data.RData: 200 x 15 tibble containing IHC staining intensities for pIRAK4, pSTAT6 and STAT6 staining in CLL and healthy tissue, along with meta data (including clinical outcomes) on each patient sample
	patMeta.RData: tibble containing all patient genetic data
	survT.RData: tibble containing disease progression data for patients in screen
inst/doc	Contains all HTML files generated by running .Rmd files in vignettes/src
inst/ext	Contains data files in tsv format, plus additional non RData files required for analyses
inst/images	Contains all images files used in the analysis:
	Fig1A.pdf: graphical overview of experimental process
	Fig1B.pdf: graphical overview of stimuli pathways
	CLL1_I3_STAT6.png: image of CLL infiltrated LN, stained for STAT6
	CLL1_I3_pIRAK4.png: image of CLL infiltrated LN, stained for pIRAK4
	CLL1_I3_pSTAT6.png: image of CLL infiltrated LN, stained for pSTAT6
	LK2_B4_STAT6.png: image of non-neoplastic LN, stained for STAT6
	LK2_B4_pIRAK4.png: image of non-neoplastic LN, stained for pIRAK4
	LK2_B4_pSTAT6.png: image of non-neoplastic LN, stained for pSTAT6
inst/shiny	Contains code for shiny app and associated data, found here
vignettes	CLLCytokineScreen2021.Rmd: script to produce vignette replicating all figures from paper
vignettes/src	figure1.Rmd etc: all individual scripts for each figure of the paper