Gene-CluEDO: Most likely order of genes in a gene cluster

Certain gene clusters, like the Hox cluster, are likely to have evolved from a single ancestral gene. This software aims at determining the most likely order in this evolution.

README

(included from project) Christian Höner zu Siederdissen - Gene-CluEDO

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generalized Algebraic Dynamic Programming Homepage

Gene-CluEDO: Gene Cluster Evolution Determined Order

The first paper describes the biological problem. The 2nd and 3rd paper provide algorithmic background.

  1. Prohaska, Sonja J. and Berkemer, Sarah and Externbrink, Fabian and Gatter, Thomas
    and Retzlaff, Nancy and The Students of the Graphs and Biological Networks Lab 2017
    and Hoener zu Siederdissen, Christian and Stadler, Peter F.
    Expansion of Gene Clusters and the Shortest Hamiltonian Path Problem
    2017
    preprint: http://www.bioinf.uni-leipzig.de/~choener/pdfs/pro-ber-2017.pdf

  2. Hoener zu Siederdissen, Christian and Prohaska, Sonja J. and Stadler, Peter F.
    Algebraic Dynamic Programming over General Data Structures
    2015, BMC Bioinformatics
    oa: https://doi.org/10.1186/1471-2105-16-S19-S2

  3. Hoener zu Siederdissen, Christian and Prohaska, Sonja J. and Stadler, Peter F.
    Dynamic Programming for Set Data Types
    2014, Lecture Notes in Bioinformatics, 8826,
    preprint: http://www.bioinf.uni-leipzig.de/~choener/pdfs/hoe-pro-2014.pdf

This program accepts a matrix with distances between nodes (see below for an example). It then proceeds to calculate the Hamiltonian path with the shortest distance between each pair of nodes, where the path has to travel from the start, then to all other nodes, finally stopping at the last node.

We further calculate all neighbour probabilities via Inside/Outside. This means that for any two nodes we calculate the weight of the edge between these two nodes. The weight is between [0, ... ,1] where 0 denotes the the nodes are almost surely not direct neighbours on a weighted-randomly drawn path, while 1 denotes that they almost surely are.

Finally, we calculate the probability that a node is one of the terminal nodes in the Hamiltonian path, i.e. either the first or the last node.

Installation / Pre-compiled Binaries

Input data used for the Expansion of Gene Clusters paper

The data sets are available together with the sources or the binary release. Check the data folder. The run-all.sh script runs the four examples.

The Biological Problem We Solve

Wikipedia on Hox clusters.

Hox clusters are a set of genes that are linearly ordered. The genes are (assumed) to have a single originating gene, and repeated duplication has led to the cluster with unknown duplication tree.

The long time scales involved make it hard to produce a tree that can be trusted. This program therefore produces summary information in the form of edge path probabilities.

Example matrix:

In this artificial distance matrix, we have prime numbers as distances between nodes. Store the matrix in a file, say mat.dat.

#   A   B   C   D   E
A   0   2   3   5   7
B   2   0  11  13  17
C   3  11   0  19  23
D   5  13  19   0  27
E   7  17  23  27   0

Now, run the algorithm ./GeneCluEDO -o output.run ./mat.dat. After the program has run, output.run contains the a wealth of information about the input. The maximum likelihood path, the edge weights, end probabilities, and maximum expected accuracy path are calculated. Two additional files, here output.boundary.svg, and output.edge.svg are produced. The boundary plot provides graphical output of the probability that a node (or gene) is the start or end node. The edge probability plot provides probabilities for each edge (i,j) between nodes. This shows the most likely neighbors, and therefore genetic relationship, over all possible gene orders.

Contact

Christian Hoener zu Siederdissen
Leipzig University, Leipzig, Germany
choener@bioinf.uni-leipzig.de
http://www.bioinf.uni-leipzig.de/~choener/

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Installation from sources via stack:

This software can be compiled and installed using stack in a small number of steps. Note that some packages only provide a library and no executable.
  1. Prepare a directory for the software:
    mkdir ~/haskell/
    cd ~/haskell
    (If you choose another name, replace accordingly below)
  2. Install stack itself. Binaries are available here. Copy the binaries into the ~/haskell directory.
  3. Download the Gene-CluEDO software:
    ~/haskell/stack unpack Gene-CluEDO
    ls
    This unpacks the newest version of Gene-CluEDO, the version itself being referred to as -VERSION, which you should see via ls.
  4. Compile:
    cd ~/haskell/Gene-CluEDO-VERSION
    ~/haskell/stack build
  5. Execute (you can find the executable names, if any, in the cabal as executable build targets):
    ~/haskell/stack exec EXECUTABLE
  6. Optionally, install any executables into ~/haskell/bin/
    . This simplifies actually running the programs later on. mkdir -p ~/haskell/bin
    ~/haskell/stack install --local-bin-path ~/haskell/bin