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# ISAnalytics <a href='https://bioconductor.org/packages/3.12/bioc/html/ISAnalytics.html'><img src='man/figures/logo.png' align="right" height="250" /></a>
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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](https://calabrialab.github.io/ISAnalytics/)
- For the devel version: [ISAnalytics Website
dev](https://calabrialab.github.io/ISAnalytics/dev)
# Installation
## Installation from bioconductor
RELEASE version:
``` r
if (!requireNamespace("BiocManager", quietly = TRUE))
install.packages("BiocManager")
BiocManager::install("ISAnalytics")
```
DEVEL version:
``` r
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:
``` r
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:
``` r
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.