TADdyn is a Python library that allows to model and explore single or time-series 3C-based data. These datasets are constituted by interaction matrices that describe distinct stages of naturally occurring or induced cellular process such as the cell trans-differentiation, or reprogramming. With TADdyn the user can load at once the raw and normalised interaction binned matrices (Hi-C like matrices) at each of the experimental stages, build 4D models, and finally, extract structural properties from the models. The 4D models reproduce the expected interaction patterns at the experimental time-points, and also describe the structural modifications at intermediate moments (between stages) under the hypothesis that the changes occurring between consecutive experimental time-points are smooth. To do this, TADdyn is designed as a combination of restraint-based modelling, and steered Langevin dynamics of Physics-based chromatin models.

Documentation

Install LAMMPS as a shared library

1 - Download lammps

git clone -b stable https://github.com/lammps/lammps.git mylammps

2 - Download the colvar modified version

git clone https://github.com/david-castillo/colvars

3 - Update the user-defined colvars library

./colvars/update-colvars-code.sh ./mylammps/

4 - Compile colvars library

cd ./mylammps/lib/colvars

make -f Makefile.g++

5 - Install lammps as a shared library

cd ../../src/

include "-DLAMMPS_EXCEPTIONS" in the LMP_INC line in src/MAKE/Makefile.serial

make yes-user-colvars

make yes-molecule

make serial mode=shlib

make install-python

cd ../../

Install packages

conda install -y scipy # scientific computing in python

conda install -y numpy # scientific computing in python

conda install -y matplotlib # to produce plots

conda install -y jupyter # this notebook :)

conda install -y -c https://conda.anaconda.org/bcbio pysam # to deal with SAM/BAM files

conda install -y -c https://conda.anaconda.org/salilab imp # for 3D modeling

conda install -y -c bioconda mcl # for clustering

Install TADdyn

1 - Download TADdyn from the Github repository

git clone https://github.com/david-castillo/TADbit.git -b TADdyn TADdyn

2 - Install TADdyn

cd TADdyn

python setup.py install

cd ..

Try TADdyn

cd test/Sox2

python test_TADdyn_on_Sox2.py

Citation

Please, cite this article if you use TADdyn.

Marco Di Stefano, Ralph Stadhouders, Irene Farabella, David Castillo, François Serra, Thomas Graf, Marc A. Marti-Renom. Transcriptional activation during cell reprogramming correlates with the formation of 3D open chromatin hubs Nat Commun 11, 2020, 2564; https://doi.org/10.1038/s41467-020-16396-1.

Methods implemented in TADdyn

In the actual implementation, TADdyn relies on TADbit for the preparation of the 3C-based datasets from mapping to normalization, and on LAMMPS [Plimpton] for the implementation of the simulations.

Bibliography

[Plimpton]

Plimpton, S. Fast Parallel Algorithms for Short-Range Molecular Dynamics. J Comp Phys 117, 1-19 (1995) and Fiorin, G., Klein, M.L. & Hénin, J. Using collective variables to drive molecular dynamics simulations. Molecular Physics 111, 3345-3362 (2013).