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README.md

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Supporting repository for the publication:

"Unraveling the Glycosphingolipid Metabolism Leveraging Transcriptome-weighted Network Analysis on Neuroblastic Tumors" by

Arsenij Ustjanzew (1*), Annekathrin Silvia Nedwed (1), Federico Marini (1, 2), Roger Sandhoff (3, 4), Jörg Faber (5, 6), and Claudia Paret (5, 6)

  1. Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center of the Johannes Gutenberg-University Mainz, 55131, Mainz, Germany

  2. Research Center for Immunotherapy (FZI), Langenbeckstraße 1, 55131 Mainz, Germany

  3. Lipid Pathobiochemistry, German Cancer Research Center, 69120 Heidelberg, Germany

  4. Helmholtz-Institute for Translational Oncology Mainz (HI-TRON), 55131 Mainz, Germany

  5. Department of Pediatric Hematology/Oncology, Center for Pediatric and Adolescent Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, 55131, Mainz, Germany

  6. University Cancer Center (UCT), University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany

Overview

This repository contains following files:

  • substrate_graph.Rds - contains the used GSL network as igraph object
  • generating_network.Rmd - contains the steps of GSL network generation
  • read_xenabrowser_data.R - Code for reading the TCGA-GTEx-TARGET data, creating a SummarizedExperiment object, and subsetting it to TARGET
  • functions.R - contain functions for: 1) Assigning expression values to edges of an igraph object, 2) computing the reaction activity of a gene expression matrix, 3) computing transition probabilities with different adjustment options
  • NB_GNB_pathanalysis.Rmd - contains the full analysis with visualizations of the TARGET NB/GNB dataset
  • NB_GN_pathanalysis.Rmd - contains the full analysis with visualizations of the GSE147635 NB/GN dataset
  • NB_GN_FC_image.Rmd - Code for creating figures of the Ganglioside graph and fold-change dotplot (Neuroblastoma vs. Ganglioneuroma)
  • NB_GNB_FC_image.Rmd - Code for creating figures of the Ganglioside graph and fold-change dotplot (Neuroblastoma vs. Ganglioneuroblastoma)
  • NBmycn_GNB_FC_image.Rmd - Code for creating figures of the Ganglioside graph and fold-change dotplot (Neuroblastoma MYCN amplified vs. Ganglioneuroblastoma)
  • NBmycn_NB_FC_image.Rmd - Code for creating figures of the Ganglioside graph and fold-change dotplot (Neuroblastoma MYCN amplified vs. Neuroblastoma without MYCN amplification)

Notes

This repository does not contain the used data (input data of the Rmd scripts) nor the output images/ files generated during the analysis.

  • The TARGET NB/GNB dataset has to be downloaded and preprocessed from here ("A combined cohort of TCGA, TARGET and GTEx samples"). The used file were the "gene expression RNAseq - RSEM expected_count" ("TcgaTargetGtex_gene_expected_count") and the "phenotype - TCGA TARGET GTEX selected phenotypes" ("TcgaTargetGTEX_phenotype.txt") These data was combined to a SummarizedExperiment class object and subsetted to Neuroblastoma samples.
  • The raw fastq files of the GSE147635 dataset were downloaded from Gene Expression Omnibus and processed as described in the manuscript.

The R Markdown files are not intended to be knitted to a document and are meant to represent steps of the analysis.