Multi-omics integration of malignant peripheral nerve sheath tumors (MPNST) identifies potential targets based on chromosome 8q (chr8q) status

Since chr8q gain is associated with high-grade transformation in MPNST and inferior overall survival, we integrate multi-omics data to understand drivers and potential targets based on chr8q status. To do this, we collected new proteomics data and ran correlations between omics expression and chr8q copy number in MPNST patient-derived xenografts (PDX) in addition to pathway analyses, network analyses, drug sensitivity predictions, fluorescent in situ hybridization, and viability studies.

Install dependencies

For this analysis there are numerous dependencies which are listed in the installDependences.R script.

Initial proteomics processing located in proteomics

These proteomics processing files are used to generate dataframes of relative protein abundance. While many of them are designed to be run internally at PNNL, they can be used to get a sense of how the mass spectrometry reads were mapped to proteins and phosphosites.

Create study design tables

0-create_study_design_tables.Rmd

Initial global proteomics processing

1-process_global_data.Rmd

Initial phospho proteomics processing

2-process_phospho_data.Rmd

Prep KSTAR input

2.5-process_KSTAR_input.Rmd Not currently used but available in case of future need.

Normalization and batch correction

3-normalize_and_batch_correction.Rmd

Upload crosstabs to Synapse

4-push_to_synapse.Rmd

Analysis located in proteomics

This directory contains the scripts for multi-omics analysis of chr8q gain in MPNST for the Garana et al. manuscript.

Multi-omics correlations and GSEA

5-panSEA_using_helper.R Uses functions available in panSEA_helper_20240913.R script.

Simulation study for GSEA adapted to shuffle tied genes/proteins

GSEA_ties_simulation_20240909_v2.R Also generates plots for figure S2

Figure generation located in figures

This directory contains the tools needed to regenerate the figures for the Garana et al. manuscript.

Figure 1: correlations

Figure1_20250410.R

Figure S1: histograms

FigureS1_20250409.R

Figure 2: enrichment analyses

• Figure2_20250429.R
• networkAnalysis.R

Figure S3: drivers of enrichment

• Transcription factor targets: FigureS3_TF_20250418.R
• Kinase substrates: FigureS3_kinase_20250418.R

Figure 3: drug sensitivity predictions

Figure3_20250513.R

Drug screen

• drugScreening.R: only used for IC50 t-tests
• fit_curve.py: calculates area under the curve values; not currently used; adapted from: https://github.com/PNNL-CompBio/coderdata/blob/main/coderbuild/utils/fit_curve.py

FAK analysis located in Chr8_FAK.R

This directory contains additional analysis studying the role of FAK in chromosome 8 mediated activity in MPNST. This analysis is not included in the multi-omics study but rather in a separate chr8 study focused on FAK.