https://github.com/mschubert/toxicgenes

https://github.com/mschubert/toxicgenes

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• Host: GitHub
• URL: https://github.com/mschubert/toxicgenes
• Owner: mschubert
• License: gpl-3.0
• Created: 2019-06-17T11:40:57.000Z (over 5 years ago)
• Default Branch: master
• Last Pushed: 2024-12-14T15:23:35.000Z (about 1 month ago)
• Last Synced: 2024-12-14T16:28:32.597Z (about 1 month ago)
• Language: R
• Size: 922 KB
• Stars: 0
• Watchers: 1
• Forks: 0
• Open Issues: 7
• Metadata Files:
  • Readme: README.md
  • License: LICENSE

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README

        
# Analysis code for "A compendium of Amplification-Related Gain Of Sensitivity (ARGOS) genes in human cancer"

> Chromosomal gains are among the most frequent somatic genetic alterations

> occurring in cancer. While the effect of sustained oncogene expression has

> been characterized, the impact of copy-number gains affecting

> collaterally-amplified “bystander” genes on cellular fitness remains less

> understood. To investigate this, we built a comprehensive map of dosage

> compensations across human cancers by integrating expression and copy number

> profiles from over 8,000 TCGA tumors and CCLE cell lines. Further, we

> analyzed the effect of gene overexpression across 17 human cancer ORF screens

> to provide an overview of genes that prove toxic to cancer cells when

> overexpressed. Combining these two independent approaches we propose a class

> of ‘Amplification-Related Gain Of Sensitivity’ (ARGOS) genes. These genes are

> located in commonly amplified regions of the genome, have lower expression

> levels than expected by their copy-number status, and are toxic to cancer

> cells when overexpressed. We experimentally validated CDKN1A and RBM14 as

> high-confidence pan-cancer ARGOS genes in lung and breast cancer cell line

> models. We additionally suggest that RBM14’s mechanism of toxicity involves

> altered DNA damage response and innate immune signaling processes following

> gene overexpression. Finally, we provide a comprehensive catalog of

> compensated, toxic, and ARGOS genes as a community resource.

## Analysis directories

The main Analysis steps are performed in the following directories:

* `data` - Creating the analytical data sets

* `model_compensation` - The compensation analysis

* `model_orf` - The ORF toxicity analysis

* `misc` - Specific questions and reviewer requests

* `report` - The scripts to create all figures in the manuscript

Those can be run via the `snakemake` workflow manager once all dependencies are

met.

All other directories contain analyses that are not part of the publication.

## Dependencies

* All required R packages and their versions are listed in `renv.lock`.

* The `ebits` toolkit and setup according to the project README

* The ORF and TCGA data sets from their respective publications