{"id":39554391,"url":"https://github.com/jackhump/two_tdp-43_mutant_mice","last_synced_at":"2026-01-18T07:00:45.272Z","repository":{"id":185141781,"uuid":"93189427","full_name":"jackhump/Two_TDP-43_Mutant_Mice","owner":"jackhump","description":"scripts written for Fratta et al \"Endogenous TDP-43 mutant mice have novel gain of splicing function and ALS characteristics in vivo\"","archived":false,"fork":false,"pushed_at":"2019-02-15T13:04:40.000Z","size":35756,"stargazers_count":0,"open_issues_count":0,"forks_count":0,"subscribers_count":2,"default_branch":"master","last_synced_at":"2023-07-31T21:25:28.332Z","etag":null,"topics":[],"latest_commit_sha":null,"homepage":"","language":"R","has_issues":true,"has_wiki":null,"has_pages":null,"mirror_url":null,"source_name":null,"license":null,"status":null,"scm":"git","pull_requests_enabled":true,"icon_url":"https://github.com/jackhump.png","metadata":{"files":{"readme":"README.md","changelog":null,"contributing":null,"funding":null,"license":null,"code_of_conduct":null,"threat_model":null,"audit":null,"citation":null,"codeowners":null,"security":null,"support":null,"governance":null}},"created_at":"2017-06-02T17:35:35.000Z","updated_at":"2023-07-31T21:25:29.302Z","dependencies_parsed_at":null,"dependency_job_id":"cae7b95d-6567-46dc-ac21-3c77442b0303","html_url":"https://github.com/jackhump/Two_TDP-43_Mutant_Mice","commit_stats":null,"previous_names":["jackhump/two_tdp-43_mutant_mice"],"tags_count":null,"template":null,"template_full_name":null,"purl":"pkg:github/jackhump/Two_TDP-43_Mutant_Mice","repository_url":"https://repos.ecosyste.ms/api/v1/hosts/GitHub/repositories/jackhump%2FTwo_TDP-43_Mutant_Mice","tags_url":"https://repos.ecosyste.ms/api/v1/hosts/GitHub/repositories/jackhump%2FTwo_TDP-43_Mutant_Mice/tags","releases_url":"https://repos.ecosyste.ms/api/v1/hosts/GitHub/repositories/jackhump%2FTwo_TDP-43_Mutant_Mice/releases","manifests_url":"https://repos.ecosyste.ms/api/v1/hosts/GitHub/repositories/jackhump%2FTwo_TDP-43_Mutant_Mice/manifests","owner_url":"https://repos.ecosyste.ms/api/v1/hosts/GitHub/owners/jackhump","download_url":"https://codeload.github.com/jackhump/Two_TDP-43_Mutant_Mice/tar.gz/refs/heads/master","sbom_url":"https://repos.ecosyste.ms/api/v1/hosts/GitHub/repositories/jackhump%2FTwo_TDP-43_Mutant_Mice/sbom","scorecard":null,"host":{"name":"GitHub","url":"https://github.com","kind":"github","repositories_count":286080680,"owners_count":28532579,"icon_url":"https://github.com/github.png","version":null,"created_at":"2022-05-30T11:31:42.601Z","updated_at":"2026-01-18T00:39:45.795Z","status":"online","status_checked_at":"2026-01-18T02:00:07.578Z","response_time":98,"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":"2026-01-18T07:00:25.246Z","updated_at":"2026-01-18T07:00:45.247Z","avatar_url":"https://github.com/jackhump.png","language":"R","funding_links":[],"categories":[],"sub_categories":[],"readme":"#### Fratta, Sivakumar, Humphrey, Lo, Ricketts, et al, 2018\n#### *Endogenous TDP-43 mutant mice have novel gain of splicing function and ALS characteristics in vivo*\n#### in press at EMBO Journal\n#### 2018\n\nThis GitHub repository contains all scripts to recreate the key bioinformatic analyses of the paper.\n\nall scripts written by Jack Humphrey, Kitty Lo, Prasanth Sivakumar and Shannon Edwards\n\n## Dependencies:\n\nMac OS X or Linux\n\nbedtools v2.24.0\n\nbigWigSummary (http://hgdownload.soe.ucsc.edu/admin/exe/macOSX.x86_64/bigWigSummary)\n\n*R \u003e= 3.3.2*\n- dplyr\n- ggplot2\n- stringr\n- biostrings\n- data.table\n- gridExtra\n- optparse\n- smoother (no longer available on CRAN for R 3.4.3, have to build from tarball - sorry! )\n- TTR\n\n*python 2.7.10*\n- pybedtools\n- argparse\n\n\n## Installation\n\n1. clone github repository to your computer\n1. unzip the data:\n\n```\ntar -xzvf data.tar.gz\n```\n\n3. download the PhyloP 60way conservation scores from UCSC:\n\n```\nwget http://hgdownload.cse.ucsc.edu/goldenpath/mm10/phyloP60way/mm10.60way.phyloP60way.bw\n```\n\n\n## A note on data pre-processing\n\nAll RNA-seq data was processed using the Plagnol lab RNA-seq pipeline (github.com/plagnollab/RNASeq_pipeline). \n\nSamples were aligned to mm10 with STAR.\n\nReads that overlap exons were counted with HTSeq. \n\nDifferential gene expression was computed with DESeq2.\n\nDifferential splicing was computed with SGSeq.\n\nAll iCLIP data was downloaded from iCOUNT in low FDR clusters.\n\n## Analysis scripts used in the paper:\n\n###  - 5A,B) RNA maps \t\n\n-  `RNA_maps/whole_intron_cluster_coverage.py`\t\n-  `RNA_maps/plot_whole_intron_coverage.R`\n-  `RNA_maps/create_RNAmaps.sh`\n\n`whole_intron_cluster_coverage.py` takes a BED file of exons or introns and intersects them with a second BED file of iCLIP clusters.\n\n`plot_whole_intron_coverage` composes the RNAmaps from a set of introns and exons. Per-gene coverages are normalised by the total number of genes to create a per-nucleotide coverage.\n\nReproduce the plots in 5A) and 5B) by running: \n\n```\ncd RNAmaps/\nsh create_RNAmaps.sh\n```\n\n\n### 5C) conservation\n- `conservation/conservation.R`\n\nCalculates per-exon conservation score for groups of exons.\n\nbigWigSummary must be downloaded from http://hgdownload.soe.ucsc.edu/admin/exe/macOSX.x86_64/bigWigSummary and installed on your $PATH\n\nReproduce figure 5C):\n\n```\ncd conservation/\nRscript conservation.R\n```\n\n### 5D) Differential expression \n- `differential_expression/skiptic_cryptic_expression.R`\n\nRunning this script compares the DESeq2 differential gene expression results with the lists of genes that contain extreme splicing events.\n\n### 5E) functional prediction\n- `NMD_prediction/NMD_prediction.R`\n- `NMD_prediction/bring_everything_together.R`\n\nThis needs explaining. \n\n### Expanded View 1\nA,D) pie charts\n- `differential_splicing/makePieChartsAllEvents.R`\n\ncreates pie charts of splicing variant types. \n\n\n### Expanded View 4\nA,B) long genes\n- `differential_expression/all_mice_TDP-43_long_genes.R`\n\nTakes each DESeq2 differential expression results file and creates a signed Z-score for each gene ( Z = qnorm(1 - (P / 2)  ) with the sign of the direction of the fold change. Genes are then ranked and binned into groups of 200 genes. The mean intron length for each gene according to GENCODE annotation is then matched and compared.\n\n### Appendix S6 - MA plots \n- `ma_plots/make_MA_plots.R`\n\nTakes the SGSeq differential splicing results file and plots the mean reads that support each splice event against the log2 fold change of that splice event.\n\n\n### Appendix S7 - Permutation testing\n- permutation/permute_qq.R\n- permutation/permute_100_sgseq.sh\n- permutation/plot_permutations.R\n\nThis needs explaining.\n\n\n","project_url":"https://awesome.ecosyste.ms/api/v1/projects/github.com%2Fjackhump%2Ftwo_tdp-43_mutant_mice","html_url":"https://awesome.ecosyste.ms/projects/github.com%2Fjackhump%2Ftwo_tdp-43_mutant_mice","lists_url":"https://awesome.ecosyste.ms/api/v1/projects/github.com%2Fjackhump%2Ftwo_tdp-43_mutant_mice/lists"}