{"id":24529907,"url":"https://github.com/mschubert/toxicgenes","last_synced_at":"2025-09-07T16:34:01.142Z","repository":{"id":212833622,"uuid":"192335526","full_name":"mschubert/ToxicGenes","owner":"mschubert","description":null,"archived":false,"fork":false,"pushed_at":"2025-01-28T12:08:59.000Z","size":959,"stargazers_count":1,"open_issues_count":7,"forks_count":0,"subscribers_count":1,"default_branch":"master","last_synced_at":"2025-03-15T18:22:36.041Z","etag":null,"topics":[],"latest_commit_sha":null,"homepage":null,"language":"R","has_issues":true,"has_wiki":null,"has_pages":null,"mirror_url":null,"source_name":null,"license":"gpl-3.0","status":null,"scm":"git","pull_requests_enabled":true,"icon_url":"https://github.com/mschubert.png","metadata":{"files":{"readme":"README.md","changelog":null,"contributing":null,"funding":null,"license":"LICENSE","code_of_conduct":null,"threat_model":null,"audit":null,"citation":null,"codeowners":null,"security":null,"support":null,"governance":null,"roadmap":null,"authors":null,"dei":null,"publiccode":null,"codemeta":null,"zenodo":null,"notice":null,"maintainers":null,"copyright":null,"agents":null,"dco":null,"cla":null}},"created_at":"2019-06-17T11:40:57.000Z","updated_at":"2025-01-29T06:09:37.000Z","dependencies_parsed_at":null,"dependency_job_id":"3c0c5b32-319e-46a4-ae5c-384d138a8bf5","html_url":"https://github.com/mschubert/ToxicGenes","commit_stats":null,"previous_names":["mschubert/toxicgenes"],"tags_count":1,"template":false,"template_full_name":null,"purl":"pkg:github/mschubert/ToxicGenes","repository_url":"https://repos.ecosyste.ms/api/v1/hosts/GitHub/repositories/mschubert%2FToxicGenes","tags_url":"https://repos.ecosyste.ms/api/v1/hosts/GitHub/repositories/mschubert%2FToxicGenes/tags","releases_url":"https://repos.ecosyste.ms/api/v1/hosts/GitHub/repositories/mschubert%2FToxicGenes/releases","manifests_url":"https://repos.ecosyste.ms/api/v1/hosts/GitHub/repositories/mschubert%2FToxicGenes/manifests","owner_url":"https://repos.ecosyste.ms/api/v1/hosts/GitHub/owners/mschubert","download_url":"https://codeload.github.com/mschubert/ToxicGenes/tar.gz/refs/heads/master","sbom_url":"https://repos.ecosyste.ms/api/v1/hosts/GitHub/repositories/mschubert%2FToxicGenes/sbom","scorecard":null,"host":{"name":"GitHub","url":"https://github.com","kind":"github","repositories_count":274064438,"owners_count":25216323,"icon_url":"https://github.com/github.png","version":null,"created_at":"2022-05-30T11:31:42.601Z","updated_at":"2022-07-04T15:15:14.044Z","status":"online","status_checked_at":"2025-09-07T02:00:09.463Z","response_time":67,"last_error":null,"robots_txt_status":"success","robots_txt_updated_at":"2025-07-24T06:49:26.215Z","robots_txt_url":"https://github.com/robots.txt","online":true,"can_crawl_api":true,"host_url":"https://repos.ecosyste.ms/api/v1/hosts/GitHub","repositories_url":"https://repos.ecosyste.ms/api/v1/hosts/GitHub/repositories","repository_names_url":"https://repos.ecosyste.ms/api/v1/hosts/GitHub/repository_names","owners_url":"https://repos.ecosyste.ms/api/v1/hosts/GitHub/owners"}},"keywords":[],"created_at":"2025-01-22T07:53:02.891Z","updated_at":"2025-09-07T16:34:01.052Z","avatar_url":"https://github.com/mschubert.png","language":"R","funding_links":[],"categories":[],"sub_categories":[],"readme":"# Analysis code for \"A compendium of Amplification-Related Gain Of Sensitivity (ARGOS) genes in human cancer\"\n\n\u003e Chromosomal gains are among the most frequent somatic genetic alterations\n\u003e occurring in cancer. While the effect of sustained oncogene expression has\n\u003e been characterized, the impact of copy-number gains affecting\n\u003e collaterally-amplified “bystander” genes on cellular fitness remains less\n\u003e understood. To investigate this, we built a comprehensive map of dosage\n\u003e compensations across human cancers by integrating expression and copy number\n\u003e profiles from over 8,000 TCGA tumors and CCLE cell lines. Further, we\n\u003e analyzed the effect of gene overexpression across 17 human cancer ORF screens\n\u003e to provide an overview of genes that prove toxic to cancer cells when\n\u003e overexpressed. Combining these two independent approaches we propose a class\n\u003e of ‘Amplification-Related Gain Of Sensitivity’ (ARGOS) genes. These genes are\n\u003e located in commonly amplified regions of the genome, have lower expression\n\u003e levels than expected by their copy-number status, and are toxic to cancer\n\u003e cells when overexpressed. We experimentally validated CDKN1A and RBM14 as\n\u003e high-confidence pan-cancer ARGOS genes in lung and breast cancer cell line\n\u003e models. We additionally suggest that RBM14’s mechanism of toxicity involves\n\u003e altered DNA damage response and innate immune signaling processes following\n\u003e gene overexpression. Finally, we provide a comprehensive catalog of\n\u003e compensated, toxic, and ARGOS genes as a community resource.\n\n## Analysis directories\n\nThe main Analysis steps are performed in the following directories:\n\n* `data` - Creating the analytical data sets\n* `model_compensation` - The compensation analysis\n* `model_orf` - The ORF toxicity analysis\n* `misc` - Specific questions and reviewer requests\n* `report` - The scripts to create all figures in the manuscript\n\nThose can be run via the `snakemake` workflow manager once all dependencies are\nmet.\n\nAll other directories contain analyses that are not part of the publication.\n\n## Dependencies\n\n* All required R packages and their versions are listed in `renv.lock`.\n* The `ebits` toolkit and setup according to the project README\n* The ORF and TCGA data sets from their respective publications\n","project_url":"https://awesome.ecosyste.ms/api/v1/projects/github.com%2Fmschubert%2Ftoxicgenes","html_url":"https://awesome.ecosyste.ms/projects/github.com%2Fmschubert%2Ftoxicgenes","lists_url":"https://awesome.ecosyste.ms/api/v1/projects/github.com%2Fmschubert%2Ftoxicgenes/lists"}