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[![Build Status](]( # *TitanCNA* TitanCNA a R/Bioconductor package for analyzing subclonal copy number alterations (CNA) and loss of heterozygosity (LOH) in whole genome and exome sequencing of tumours. Ha, G., et al. (2014). [TITAN: Inference of copy number architectures in clonal cell populations from tumour whole genome sequence data. Genome Research, 24: 1881-1893.]( (PMID: 25060187) ## Contact Gavin Ha Fred Hutchinson Cancer Research Center contact: <> or <> Date: January 2, 2019 Website: []( ## Table of Contents * [Links](#links) * [News](#news) * [Installation](#installation) * [Usage](#usage) * [Vignette in TitanCNA R package](#vignette-in-titancna-r-package) * [Acknowledgements](#acknowledgements) * [License](#software-license) ## Links Snakemake Workflow: **10X Snakemake Workflow:** Google Groups:!forum/titancna TitanCNA website: KRONOS TITAN Workflow: Publication in Genome Research: ## News (See [NEWS](NEWS) for previous version notes) ### August 9, 2018 Improved parameter inference by handling errors and allowing EM to continue until convergence. This fixes runs that previously would fail because samples had very low tumor content. ### July 26, 2018 Snakemake workflow for 10X Genomics whole genome sequencing data is now included in another Git repo. ### TitanCNA version 1.17.1 changes 1) New functions: - `correctIntegerCN()`: recomputes high-level copy number that is capped by the maximum CN state. Performs two tasks - (1) correct log ratio based on purity and ploidy, and then convert to decimal CN value; (2) Correct bins and segments in which the original predicted integer copy number was assigned the maximum CN state; bins and segments for all of chromosome X are also corrected, if provided in the input. 2) Modified functions: - `plotSegmentMedians()` and `plotCNlogRByChr()`: includes argument to show color-coding for corrected copy number; defaults to TRUE for this argument. 3) Removed functions/manual/dependencies: - `extractAlleleReadCounts()` - `Rsamtools` dependency ### TitanCNA version 1.15.0 changes 1) 10X Genomics analysis - Please see [scripts](scripts/) for instructions on running the 10X Genomics analysis. 2) New script to help **select optimal solutions**. Please see [scripts/R_scripts]( 3) Added snakemake pipeline for entire TITAN workflow Please see [scripts/snakemake](scripts/snakemake). 4) New function: - `plotSegmentMedians()` - `loadHaplotypeAlleleCounts()`: loads input allele counts with phasing information - `plotHaplotypeFraction()`: results from 10X Genomics WGS data with phasing of haplotype blocks 5) Modified features (no changes for user-accessible functions): - updateParameters: coordinate descent estimate of ploidy update uses previously estimated normal parameter from the same corodinate descent iteration ; leads to faster convergence ## Installation ### Install TitanCNA R package from github From within R-3.3.2 or higher, ``` install.packages("devtools") library(devtools) install_github("gavinha/TitanCNA") ``` ### Install TitanCNA from Bioconductor From within R-3.3.2 or higher, ``` if (!requireNamespace("BiocManager", quietly=TRUE)) install.packages("BiocManager") BiocManager::install("TitanCNA") ``` ### Install other dependencies 1. Install the HMMcopy suite Please follow instructions on the HMMcopy GitHub <>. 2. Install ichorCNA Please follow instructions on the ichorCNA GitHub Wiki <>. ## Usage R scripts are provided to run the R component of the TITAN analysis using the TitanCNA R/Bioconductor package. Please go to the [scripts](scripts/) directory and look at the README there for more details. ### Snakemake workflow A [snakemake](scripts/snakemake) is also provided in this repo. This workflow will run the TITAN a set of tumour-normal pairs, starting from the BAM files and generating TitanCNA outputs. It will also perform model selection at the end of the workflow to choose the optimal ploidy and clonal cluster solutions. ## Vignette in TitanCNA R package The PDF of the vignette can be accessed from R ``` library(TitanCNA) browseVignettes(package = "TitanCNA") ``` The path of the file can also be located using ``` pathToInstall <- system.file(package = "TitanCNA") pathToPdf <- paste0(pathToInstall, "/int/doc/TitanCNA.pdf) ``` The example provided will reproduce Figure 1 in the manuscript. However, it will be slightly different because the example is only based on the analysis of chr2, not genome-wide. ## Acknowledgements TitanCNA was developed by Gavin Ha while in the laboratories of Sohrab Shah ( and Sam Aparicio ( at the Dept of Molecular Oncology, BC Cancer Agency, Vancouver, Canada. Yikan Wang and Daniel Lai have contributed code and discussions to this project. The KRONOS TITAN workflow was developed by Diljot Grewal (<>) and Jafar Taghiyar (<>). HMMcopy was co-developed by Daniel Lai and Gavin Ha. TitanCNA was inspired by existing methods including [OncoSNP]( and [PyClone]( ## Software License License: [GPLv3](LICENSE) TitanCNA R code is open source and R/Bioconductor package is under [GPLv3](LICENSE). This applies to the v1.9.0 and all subsequent versions within and obtained from Bioconductor. Users who are using TitanCNA earlier than v1.9.0 not for the purpose of academic research should contact,, and to inquire about previous licensing.