README.md

In ISAnalytics: Analyze gene therapy vector insertion sites data identified from genomics next generation sequencing reads for clonal tracking studies

ISAnalytics

ISAnalytics is an R package developed to analyze gene therapy vector insertion sites data identified from genomics next generation sequencing reads for clonal tracking studies.

In gene therapy, stem cells are modified using viral vectors to deliver the therapeutic transgene and replace functional properties since the genetic modification is stable and inherited in all cell progeny. The retrieval and mapping of the sequences flanking the virus-host DNA junctions allows the identification of insertion sites (IS), essential for monitoring the evolution of genetically modified cells in vivo. A comprehensive toolkit for the analysis of IS is required to foster clonal trackign studies and supporting the assessment of safety and long term efficacy in vivo. This package is aimed at (1) supporting automation of IS workflow, (2) performing base and advance analysis for IS tracking (clonal abundance, clonal expansions and statistics for insertional mutagenesis, etc.), (3) providing basic biology insights of transduced stem cells in vivo.

Visit the package website

You can visit the package website to view documentation, vignettes and more.

• For the release version: ISAnalytics Website release
• For the devel version: ISAnalytics Website dev

Installation

Installation from bioconductor

RELEASE version:

if (!requireNamespace("BiocManager", quietly = TRUE))
    install.packages("BiocManager")
BiocManager::install("ISAnalytics")

DEVEL version:

if (!requireNamespace("BiocManager", quietly = TRUE))
    install.packages("BiocManager")

# The following initializes usage of Bioc devel
BiocManager::install(version='devel')

BiocManager::install("ISAnalytics")

Installation from GitHub

RELEASE:

if (!require(devtools)) {
  install.packages("devtools")
}
devtools::install_github("calabrialab/ISAnalytics",
                         ref = "RELEASE_3_12",
                         dependencies = TRUE,
                         build_vignettes = TRUE)

## Safer option for vignette building issue
devtools::install_github("calabrialab/ISAnalytics",
                         ref = "RELEASE_3_12")

DEVEL:

if (!require(devtools)) {
  install.packages("devtools")
}
devtools::install_github("calabrialab/ISAnalytics",
                         ref = "master",
                         dependencies = TRUE,
                         build_vignettes = TRUE)

## Safer option for vignette building issue
devtools::install_github("calabrialab/ISAnalytics",
                         ref = "master")

Current functionality

• Import integration matrices from files: more info with vignette("How to use import functions", package = "ISAnalytics")
• Collision removal: more info with vignette("Collision removal functionality", package = "ISAnalytics")
• Aggregation: more info with vignette("Working with aggregate functions", package = "ISAnalytics")
• Re-calibration functions: compute_near_integrations
• Analysis functions: compute_abundance, comparison_matrix separate_quant_matrices, others
• Plotting functions: CIS_volcano_plot
• Utility functions

NEWS

ISAnalytics 1.0.11 (2021-04-08)

FIXES

• Fixed issue in compute_near_integrations: when provided recalibration map export path as a folder now the function works correctly and produces an automatically generated file name
• Fixed issue in aggregate_metadata: now paths to folder that contains Vispa2 stats is looked up correctly. Also, VISPA2 stats columns are aggregated if found in the input data frame independently from the parameter import_stats.

IMPROVEMENTS

• compute_abundance can now take as input aggregated matrices and has additional parameters to offer more flexibility to the user. Major updates and improvements also on documentation and reproducible examples.
• Major improvements in function import_single_Vispa2Matrix: import is now preferentially carried out using data.table::fread greatly speeding up the process - where not possible readr::read_delim is used instead
• Major improvements in function import_association_file: greatly improved parsing precision (each column has a dedicated type), import report now signals parsing problems and their location and signals also problems in parsing dates. Report also includes potential problems in column names and signals missing data in important columns. Added also the possibility to give various file formats in input including *.xls(x) formats.
• Function top_integrations can now take additional parameters to compute top n genes for each specified group
• Removed faceting parameters in CIS_volcano_plot due to poor precision (easier to add faceting manually) and added parameters to return the data frame that generated the plot as an additional result. Also, it is now possible to specify a vector of gene names to highlight even if they’re not above the annotation threshold.

MINOR

• ISAnalytics website has improved graphic theme and has an additional button on the right that leads to the devel (or release) version of the website
• Updated vignettes

FOR DEVS ONLY

• Complete rework of test suite to be compliant to testthat v.3

ISAnalytics 1.0.10 (2021-02-17)

FIXES

• Fixed minor issues in internal functions with absolute file paths & corrected typos

ISAnalytics 1.0.9 (2021-02-15)

FIXES

• Fixed minor issues in internal functions to optimize file system alignment

ISAnalytics 1.0.8 (2021-02-10)

FIXES

• Fixed minor issues in import_association_file when checking parameters

ISAnalytics 1.0.7 (2021-02-06)

UPGRADES

• It is now possible to save html reports to file from import_parallel_Vispa2Matrices_auto and import_parallel_Vispa2Matrices_interactive, remove_collisions and compute_near_integrations

FIXES

• Fixed sample_statistics: now functions that have data frame output do not produce nested tables. Flat tables are ready to be saved to file or can be nested.
• Simplified association file check logic in remove_collisions: now function blocks only if the af doesn’t contain the needed columns

ISAnalytics 1.0.6 (2021-02-03)

UPGRADES

• Upgraded import_association_file function: now file alignment is not mandatory anymore and it is possible to save the html report to file
• Updated vignettes and documentation

ISAnalytics 1.0.5 (2020-11-16)

UPGRADES

• Greatly improved reports for collision removal functionality
• General improvements for all widget reports

ISAnalytics 1.0.4 (2020-11-10)

FIXES

• Further fixes for printing reports when widgets not available
• Added progress bar to collision processing in remove_collisions
• Updated vignettes

NEW

• Added vignette “Using ISAnalytics without RStudio support”

ISAnalytics 1.0.3 (2020-11-05)

FIXES

• Fixed missing restarts for non-blocking widgets

ISAnalytics 1.0.2 (2020-11-04)

FIXES

• Functions that make use of widgets do not interrupt execution anymore if errors are thrown while producing or printing the widgets
• Optimized widget printing for importing functions
• If widgets can’t be printed and verbose option is active, reports are now displayed on console instead (needed for usage in environments that do not have access to a browser)
• Other minor fixes (typos)

IMPORTANT NOTES

• Vignette building might fail due to the fact that package “knitcitations” is temporarily unavailable through CRAN

ISAnalytics 1.0.1 (2020-10-29)

• ISAnalytics is finally in release on bioconductor!
• Bug fixes: fixed a few bugs in importing and recalibration functions

ISAnalytics 0.99.15 (2020-10-22)

• Minor fix in import_association_file file function: added multiple strings to be translated as NA

ISAnalytics 0.99.14 (2020-10-21)

• Minor fixes in tests

ISAnalytics 0.99.13 (2020-10-19)

NEW FEATURES

• Added analysis functions CIS_grubbs and cumulative_count_union
• Added plotting functions CIS_volcano_plot

ISAnalytics 0.99.12 (2020-10-04)

NEW FEATURES

• Added analysis function sample_statistics

SIGNIFICANT USER-VISIBLE CHANGES

• aggregate_values_by_key has a simplified interface and supports multi-quantification matrices

MINOR CHANGES

• Updated vignettes
• import_parallel_Vispa2Matrices_interactive and import_parallel_Vispa2Matrices_auto now have an option to return a multi-quantification matrix directly after import instead of a list

ISAnalytics 0.99.11 (2020-09-21)

NEW FEATURES

• Added analysis functions threshold_filter, top_integrations
• Added support for multi-quantification matrices in compute_abundance

MINOR FIXES

• Fixed bug in comparison_matrix that ignored custom column names
• Fixed issues in some documentation pages

ISAnalytics 0.99.10 (2020-09-14)

ISanalytics is officially on bioconductor!

NEW FEATURES

• Added analysis functions comparison_matrix and separate_quant_matrices
• Added utility function as_sparse_matrix
• Added package logo

SIGNIFICANT USER-VISIBLE CHANGES

• Changed algorithm for compute_near_integrations
• Added support for multi-quantification matrices to remove_collisions
• Added usage of lifecycle badges in documentation: users can now see if a feature is experimental/maturing/stable etc

MINOR FIXES

• Added fix for import_single_Vispa2Matrix to remove non significant 0 values

ISAnalytics 0.99.9 (2020-09-01)

NEW FEATURES

• Added functionality: aggregate functions
• Added vignette on aggregate functions
• Added recalibration functions
• Added first analysis function (compute_abundance)

SIGNIFICANT USER-VISIBLE CHANGES

• Dropped structure ISADataFrame: now the package only uses standard tibbles
• Modified package documentation

ISAnalytics 0.99.8 (2020-08-12)

• Submitted to Bioconductor

TO DO in future updates

• [ ] Add further plot wrappers
• [ ] New functionality: raw reads flagging/filtering
• [ ] New functionality: HSCs population size estimate
• [ ] New functionality: genomic annotation
• [ ] Obtain a system to visualize interactive reports based on shiny (possibly replacing self-contained HTML reports)

Getting help

For help please contact the maintainer of the package or open an issue on GitHub.

ISAnalytics documentation built on April 9, 2021, 6:01 p.m.