nnn_paper

Code for the paper "High-Throughput DNA melt measurements enable improved models of DNA folding thermodynamics" https://doi.org/10.1101/2024.01.08.574731. "NNN" stands for "Not-Nearest-Neighbor"

Figures

Jupyter notebooks 01.1 to 01.5 correspond to the 5 main figures. Notebook 01.0_DataPrep.ipynb performs data cleaning and train-val-test split from the output of the preprocessing pipeline.

nnn

Functions used for generation of figures are defined in nnn/.

Setting up environments

Conda environments

Three major conda environments were used:

- `nnn.yml` most analysis in the repository

- `torch.yml` for training and running graph neural networks

- `nn_train.yml` for fitting and running linear regression models.
  Also available as a singularity container as defined in `nn_train.def`.

To install, make sure conda is already installed, then run conda create -f {path/to/yml/file/name}. For example, conda create -f envs/nnn.yml.

The local conda environment nnn is also directly exported to envs/nnn_environment.yml. It is provide for record keeping, and envs/nnn.yml is still recommended for installing from scratch.

RiboGraphViz

Package RiboGraphViz needs to be installed from cloned github repository, as directed at https://github.com/DasLab/RiboGraphViz.

Installing NUPACK4

NUPACK4 (v4.0.0.27) was manually installed from file as it requires a free liscence for download (https://docs.nupack.org/). As of Oct. 2024, NUPACK is temporarily free for academic personal users but may need paid subscription in the future.

1. Register a new account to get an academic liscence. Verify your email.
2. After logging in and acknowledging the liscence, you will find download links at https://www.nupack.org/download/software. Click NUPACK 4.0.0.28 to download the zip file.
3. Unzip the zip file. Go to the directory nupack-4.0.0.28/package.
4. Choose one of the four cp38 wheel files depending on your operating system. For example, nupack-4.0.0.28-cp38-cp38-macosx_10_13_x86_64.whl on macos.
5. Run conda activate nnn to activate the nnn environment.
6. Run pip install {path/to/your/nupack/whl/file} to install the NUPACK python module.

Scripts for Library design

Python scripts in scripts/ generates the sequences in the variant library and are helpful to understand library design logics.

Graph Neural Networks

Run gnn_run.py in torch envoronment, pointing to the path of the saved model state dict file.

For any questions, contact Yuxi Ke (kyx@stanford.edu).

Jan. 2024, updated Oct. 2024