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marislab / create-pptc-pdx-oncoprints

As part of an overall strategy for improving therapies for childhood cancers, the PPTC seeks to develop models for the types of tumors that will be encountered in early phase clinical testing by establishing patient derived xenografts (PDXs) from high-risk childhood cancers refractory to current standard of care treatments. Genomic profiling of these models is required to enable PPTC investigators to develop robust "responder hypotheses" when drug activity is observed. With funding provided by Alex's Lemonade Stand Foundation, we genomically characterize a major subset of 286 PDX models. We use whole exome sequencing, transcriptome sequencing, and SNPArray to characterize the tumor models. The focus on DNA and RNA sequencing data mirrors the current standard practice in most clinical diagnostics lab that use these technologies to detect the spectrum of targetable mutations, gene amplifications, and gene fusion events relevant to preclinical drug development.

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exome-sequencingrna-sequencingmutational-signaturesclassifierethnicity-analysisfusionclustering

PPTC PDX Oncoprint Generation

authors

Jo Lynne Rokita, Alvin Farrel, Khushbu Patel

contact

Jo Lynne Rokita (rokita@email.chop.edu)

organization

CHOP

status

Complete

date

Introduction

Here, we provide scripts to enable reproducible generation of Manuscript Figure 2: oncoprints by PDX histology and Figure 3: co-oncoplots for diagnosis/relapse samples in neuroblastoma, BCP-ALL, T-ALL, and osteosarcoma. This repo contains code for:

  1. Create expanded oncoprint matrices used to reproduces Figure 2 and 3

Details

  • RUN-create-full-oncoprint-revision.R
  • load-maf-maftools.R
  • cluster-scores.R
  • merge-mut-CN-fusion-matrices.R
  • co-oncoplots.R
  • merge-mut-CN-matrices.R
  • create-CN-matrices.R
  • mutation-color-function.R
  • create-complexheat-oncoprint-revision.R
  • reformat-CN-matrix-to-df.R
  • create-mut-matrices.R
  • reformat-clinical.R
  • create-mut-sigs-matrix.R
  • reformat-fusion-as-matrix.R
  • demog-color-function.R
  • reformat-fusion-for-maf-revision.R
  • install-packages.R

Software Requirements

R 3.4.3

Pipeline

# How to run:
# Download github repository in your home directory (~/)
git clone https://github.com/marislab/create-pptc-pdx-oncoprints.git

# Run script to create pie chart
Rscript ~/create-pptc-pdx-oncoprints/R/RUN-create-full-oncoprint-revision.R

Results

Results will appear in the onco-out folder

About

As part of an overall strategy for improving therapies for childhood cancers, the PPTC seeks to develop models for the types of tumors that will be encountered in early phase clinical testing by establishing patient derived xenografts (PDXs) from high-risk childhood cancers refractory to current standard of care treatments. Genomic profiling of these models is required to enable PPTC investigators to develop robust "responder hypotheses" when drug activity is observed. With funding provided by Alex's Lemonade Stand Foundation, we genomically characterize a major subset of 286 PDX models. We use whole exome sequencing, transcriptome sequencing, and SNPArray to characterize the tumor models. The focus on DNA and RNA sequencing data mirrors the current standard practice in most clinical diagnostics lab that use these technologies to detect the spectrum of targetable mutations, gene amplifications, and gene fusion events relevant to preclinical drug development.

exome-sequencingrna-sequencingmutational-signaturesclassifierethnicity-analysisfusionclustering

Languages

Language:R 100.0%