ABSOLUTE.review (v1)

Extracts the absolute copy number per cancer cell from a mixed DNA population. Use this module for the Review and Extract step in the workflow (after ABSOLUTE).

Author: Scott Carter, Matthew Meyerson, Gad Getz

Contact:

absolute-help@broadinstitute.org, http://www.broadinstitute.org/cancer/cga/cga_forums, gp-help@broadinstitute.org

Algorithm Version: ABSOLUTE 1.0.6

Introduction

The purpose of ABSOLUTE is to extract the absolute copy number per cancer cell from a mixed DNA population of tumor and normal cells, where the tumor cells derive from a predominant clone line and some number of subclones. ABSOLUTE uses segmented copy number data, together with pre-computed models of recurrent cancer karyotypes and, optionally, allelic fraction values for somatic point mutations, to infer the purity (proportions of cells that are derived from the predominant tumor clone, from tumor subclones, and from normal cells) and the ploidy (the quantity of DNA in each cell) of the tumor.  The output of ABSOLUTE then provides the absolute cellular copy number of local DNA segments and, for point mutations, the number of mutated alleles.

Module Summary

The ABSOLUTE.review module takes a version of the calls output file (*_summary.PP-calls_tab.txt) and the modes file (*_summary.PP-modes.data.RData) from ABSOLUTE.summarize that has been manually annotated as input, and outputs the final ABSOLUTE results for the samples grouped for the ABSOLUTE.summarize run.

An analyst must manually review and annotate the “calls” output file.  For more information on analyzing the ABSOLUTE data, see this page of information and tips.

Start the annotation by adding a column to the left side of the *_summary.PP-calls_tab.txt file from the ABSOLUTE.summarize module.  This new first column is where the analyst can override a default solution by entering the solution number that should be used for that row.  To keep the default solution, the corresponding cell should be left blank.  You can use Microsoft Excel for this purpose, but be sure to save the update as a tab-delimited text file. 

More details about ABSOLUTE, its parameters, and its use are available from the website of the Broad Institute CGA group.  When you refer to the information on that site, note that it discusses the ABSOLUTE algorithm in terms of the software function, and this GenePattern module executes the ExtractReviewedResults function. This document provides a summary of this information as it applies to GenePattern.

References

Carter SL, Cibulskis K, Helman E, McKenna A, Shen H, Zack T, Laird PW, Onofrio RC, Winckler W, Weir BA, Beroukhim R, Pellman D, Levine DA, Lander ES, Meyerson M, Getz G.  Absolute quantification of somatic DNA alterations in human cancer. Nat Biotechnol. 2012;30(5):413-21. (abstract and link to PDF)

More details about ABSOLUTE, its parameters and its use are available from the website of the Broad Institute Cancer Genome Analysis group.

Parameters

Name Description
reviewed pp calls file * The annotated calls file from a previous run of the ABSOLUTE.summarize module that has been reviewed and annotated by an analyst.
analyst id * The user ID of the analyst who called the solutions.  This is used for display/reporting purposes only.
modes file * The obj_summary.PP-modes.data.RData file produced by the previous run of the ABSOLUTE.summarize module.
collection name * A descriptive name for this collection of samples.  Use the same name as in the previous run of the ABSOLUTE.summarize module.  This is used for display and reporting purposes only.
copy number type *

The copy number type to assess.  Options include:

  • allelic (default)
  • total

* - required

Input Files

  1. Calls file (typically <collection.name>_summary.PP-calls_tab.txt)

A tab-delimited table detailing the called results from a previous run of the ABSOLUTE.summarize module that has been reviewed and annotated by an analyst.

  1. Modes file (typically <collection.name>_summary.PP-modes.data.RData)

The modes file from a previous run of the ABSOLUTE.summarize module.

Output Files

  1. <collection.name>.called.ABSOLUTE.table.txt

A final version of the purity/ploidy table reflecting the selected solution numbers.

  1. <collection.name>.called.ABSOLUTE.plots.pdf

A final version of the PDF reflecting the selected solution numbers.

  1. <sample.name>.ABSOLUTE.<analyst.id>.called.RData

A final RData version of the ABSOLUTE output reflecting the selected solution number.  The <sample.name> field corresponds to the values supplied in the original upstream sample-oriented ABSOLUTE module runs.

  1. <sample.name>.segtab.txt

A segmentation file modified from the HAPSEG output, with further annotations.

  1. <sample.name>_ABS_MAF.txt

(optional) If a MAF file was specified in the upstream sample-oriented ABSOLUTE module runs then a new version is supplied with further annotations.

Example Data

A set of HAPSEG example data from the CGA group is available at:

ftp://ftp.broadinstitute.org/pub/genepattern/example_files/HAPSEG_1.1.1/paper_example.zip

This can be run through HAPSEG and the output supplied to ABSOLUTE.  Note that there is a README file in the ZIP archive that provides the filenames and parameters you will need to run this example data through HAPSEG, ABSOLUTE, ABSOLUTE.summarize, and ABSOLUTE.review.

Requirements

ABSOLUTE can only be used on the GenePattern public server, as it requires a specialized installation process that prevents distribution via the repository.  Please contact the authors listed above if you have an interest in installing ABSOLUTE locally.

The ABSOLUTE.review module runs only on GenePattern 3.4.2 or above and requires R2.15.2 with the following packages:

  • numDeriv_2012.9-1
  • getopt_1.17
  • optparse_0.9.5

Each of these R packages will be automatically downloaded and installed when the module is installed.  R2.15.2 must be installed and configured independently.

 

Platform Dependencies

Task Type:
SNP Analysis

CPU Type:
any

Operating System:
any

Language:
R2.15.2

Version Comments

Version Release Date Description
1 2013-06-30 Initial version.