1. Roland Schwarz
  2. MEDICC

Overview

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MEDICC - Minimum Event Distance for Intra-tumour Copy number Comparisons

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Other requirements:

  • Unix style operating system or Cygwin on Windows
  • Python 2.7x with Biopython 1.62, Numpy/Scipy, weblogolib 3.3 (the latter should be available via "easy_install weblogo==3.3")
  • OpenFST 1.3.2 (http://www.openfst.org) compiled and in your PATH. You must ./configure OpenFST with at least the --enable-pdt and --enable-far flags. Use this exact version of OpenFST, in particular the new OpenFST versions do not seem to compile on cygwin anymore.
  • Phylip (http://evolution.genetics.washington.edu/phylip.html) compiled and in your PATH.

Installation:

  • Navigate to the "medicc_binaries" subfolder, create binary folder using "mkdir bin" if it does not exist, then compile using "make" under Cygwin or Unix
  • Navigate to the FST Framework/cExtensions subfolder (e.g lib/fstframework/cExtensions), compile using "make" under Cygwin or Unix

Running & Testing:

  • Main executable "medicc.py" takes two arguments (+options): 1) Description file indicating the position of the major and minor CNV sequences 2) Output directory

  • To check the installation run from the medicc folder: ./medicc.py --help

  • If that succeeds, run the test examples using:

./medicc.py examples/example1/desc.txt examples/example1.out -v

Troubleshooting:

  • OpenFST: The OpenFST make files install parts of the OpenFST shared libraries in a "fst" subfolder under the chosen install prefix, by default /usr/local/lib/fst You need to make sure this folder is part of both the runtime link search path (e.g. add it to ldconfig) as well as the compile time link search path. For the latter there is a variable in the cExtensions makefile that sets the -L flag that is passed to the linker. It is by default set to /usr/local/lib/fst. If you install the OpenFST libraries to a custom location the cExtensions makefile needs to be edited to match that.
  • Weblogolib: Make sure you use weblogolib 3.3 for now, not the new 3.4 version in which function calls have changed without it being mentioned in the changelog.
  • Weblogolib + Ghostscript: There is apparently an incompatibility between weblogolib 3.3 and Ghostscript 9.10 as included in the latest Ubuntu release. Before weblogolib 3.4 is the default version on all platforms (Windows easy_install still pulls 3.3 by default and doesn't find 3.4), there is little we can do. Should you encounter runtime errors that result from the weblogolib, please run medicc with the --disable-logo flag to prevent import and execution of weblogolib related code. As a result no weblogos will be created for the ancestral state reconstruction.
  • Biopython: Make sure you use Biopython 1.62 for now, as there seems to be a backcompatibility issue with the new version and the tree IO routines. According to reports from users MEDICC doesn't work with the 1.64 version. I'll fix that as soon as possible.
  • Phylip: There seems to be an installation of PHYLIP that does not contain separate "fitch", "kitsch" and "neighbor" executables, which MEDICC will look for. Instead in these installations the programs are called using "phylip fitch" commands and similar. This will lead to MEDICC not finding the executables. As a workaround, put shell scripts in your path called "fitch", "kitsch" and "neighbor" which call "phylip fitch", "phylip kitsch" and "phylip neighbor" respectively.

Contact:

Email questions, feature requests and bug reports to Roland Schwarz, roland.schwarz@mdc-berlin.de.

Please cite:

PLoS Comput Biol. 2014 Apr 17;10(4):e1003535. doi: 10.1371/journal.pcbi.1003535.
Phylogenetic quantification of intra-tumour heterogeneity.
Schwarz RF, Trinh A, Sipos B, Brenton JD, Goldman N, Markowetz F.

PLoS Med. 2015 Feb 24;12(2):e1001789. doi: 10.1371/journal.pmed.1001789.
Spatial and temporal heterogeneity in high-grade serous ovarian cancer: a phylogenetic analysis.
Schwarz RF, Ng CK, Cooke SL, Newman S, Temple J, Piskorz AM, Gale D, Sayal K, Murtaza M, Baldwin PJ, Rosenfeld N, Earl HM, Sala E, Jimenez-Linan M, Parkinson CA, Markowetz F, Brenton JD.

May 2015, Roland Schwarz