Motions

Motions is a MCMC simulation of chromatin movements within a cell nucleus using a variation of the "Strings and Binders Switch" model.

Installation

Stack is the easiest way to build and run the simulation. First you need to install stack. Installation depends on the platform. Most linux distributions should provide an easy way to get stack from repositories. Example installation on Debian 8 x64:

sudo apt-key adv --keyserver keyserver.ubuntu.com --recv-keys 575159689BEFB442
echo 'deb http://download.fpcomplete.com/debian jessie main'|sudo tee /etc/apt/sources.list.d/fpco.list
sudo apt-get update && sudo apt-get install stack -y

Detailed instructions can be found in the stack documentation.

When you have stack you can proceed with building the simulation. The following commands do everything for you:

git clone https://github.com/Motions/motions.git
cd motions
stack setup
stack build

Some dependencies require a fair amount of RAM when being built. Our experiences tell that at least 3 GB is necessary (use swap if needed).

Running the simulation

You can either use stack (if you used stack build):

stack exec -- motions

Or simply execute it from the directory containing the executable (the path may vary a little):

cd .stack-work/dist/x86_64-linux/Cabal-1.22.4.0/build/motions/
./motions

Motions supports simulation of multiple chains. Each chain bead has an associated energy vector which describes how strongly the chain interacts with various binders present inside the cell nucleus. The descriptions of chains are given using:

1. Files in the BED format to describe the different chain features that will later be translated to energy vectors.
2. One file containing lengths of chains given by a line of integers separated with spaces.
3. The simulation resolution given by a command line argument.

Example input containing chain descriptions:

1. File "feat0.bed":

   chr1     0       9
   chr1     20      29
   chr1     20      29
   chr1     40      49
   chr1     80      89
   

2. File "feat1.bed":

   chr1     10      19
   chr1     30      39
   

3. File "lengths":

   100
   

4. The resolution command line argument:

   10
   

For now we only use the required BED fields and we assume that chromosome names have the form "chrX" or "X", where X is a number, for example "chr5".

The example input describes one chain consisting of 100 base pairs with two different features appearing on it. The first feature (described in the "feat0.bed" file) appears on the following ranges: 0-9, 20-29 (twice, which means it's a stronger feature), 40-49, 80-89. The second feature (described in the "feat1.bed" file) appears on the following ranges: 10-19, 30-39.

The resolution describes how ranges of base pairs are mapped to beads, for example, if the resolution equals 10, that means the ranges beads 0, 1, ... correspond to base pair ranges 0-9, 10-19, ... respectively. The strength of a feature in a bead is equal to the number of feature appearances in the corresponding range.

In the example there are going to be 10 beads. The energy vectors are of length 2 because there are 2 features. The entries in these vectors are the corresponding feature strengths. Hence the resulting vectors are:

[1,0], [0,1], [2,0], [0,1], [1,0], [0,0], [0,0], [0,0], [1,0], [0,0]

The cell nucleus contains binders (floating binders and lamins) which interact with the chains. Energy vectors are used to determine how each bead interacts with binders of different types. The number of different binder types is equal to the length of an energy vector (which is equal to the number of chain features). At least one type of binder - the lamin - is always present in the simulation. That means there always has to be at least one BED file even if it's empty (which means no bead interacts with lamins).

The numbers of binders of each type (excluding lamins) are given in a file. Example file "binders":

50

describes that there are 50 binders of type 1 corresponding to the second entry of an energy vector (type 0 is the lamin type; it correspnds to the first entry of an energy vector). Following the example, the bead numbered 2 will interact with lamins with strength 2 and won't interact with the other 50 binders, but the bead numbered 1 won't interact with lamins and will interact with the other 50 binders with strength 1.

Run:

stack exec -- motions --help

To get a detailed description of the arguments.

An example run would be:

stack exec -- motions feat0.bed feat1.bed -l lengths -b binders -r 10 -x 10 -n 1000 -o out -s 100000 -i

The output of the simulation is given in the PDB (Protein Data Bank) format. How each energy vector, binder and chain is mapped to a string in the PDB format is described in a ".meta" file created together with the output file.