Clone the current repo

git clone https://github.com/ZhonghuiGu/HEAL.git
conda env create -f environment.yml
conda install pytorch==1.7.0 cudatoolkit=10.2 -c pytorch
wget https://data.pyg.org/whl/torch-1.7.0%2Bcu102/torch_cluster-1.5.9-cp37-cp37m-linux_x86_64.whl
wget https://data.pyg.org/whl/torch-1.7.0%2Bcu102/torch_scatter-2.0.7-cp37-cp37m-linux_x86_64.whl
wget https://data.pyg.org/whl/torch-1.7.0%2Bcu102/torch_sparse-0.6.9-cp37-cp37m-linux_x86_64.whl
wget https://data.pyg.org/whl/torch-1.7.0%2Bcu102/torch_spline_conv-1.2.1-cp37-cp37m-linux_x86_64.whl
pip install *.whl
pip install torch_geometric==1.6.3

You also need to install the relative packages to run ESM-1b protein language model.
Please see facebookresearch/esm for details.
And the ESM-1b model weight we use can be downloaded here.

python predictor.py --task mf
                    --device 0 
                    --pdb case_study/4RQ2-A.pdb 
                    --esm1b_model $esm1b_model
                    --only_pdbch false
                    --prob 0.5

$task can be among the three GO-term task -- [bp, mf, cc].
$pdb is the path of the pdb file.
$esm1b_model is the path of the ESM-1b model weight.
$prob means outputing the functions with predicted probability larger than 0.5.
$only_pdbch means using the model parameters trained on the PDBch training set solely.

The default model parameters are trained on the combination of PDBch and AFch training set, e.g., model_bpCLaf.pt, model_ccCLaf.pt and model_mfCLaf.pt.
You can also use the model parameters which are only trained on the PDBch training by setting $only_pdbch true, e.g., model_bpCL.pt, model_ccCL.pt and model_mfCL.pt.

The protein may hold the following functions of MF:
Possibility: 0.99 ||| Functions: GO:0034061, DNA polymerase activity
Possibility: 0.98 ||| Functions: GO:0140097, catalytic activity, acting on DNA
Possibility: 0.96 ||| Functions: GO:0003887, DNA-directed DNA polymerase activity
Possibility: 0.79 ||| Functions: GO:0003677, DNA binding
Possibility: 0.95 ||| Functions: GO:0016772, transferase activity, transferring phosphorus-containing groups
Possibility: 0.97 ||| Functions: GO:0016779, nucleotidyltransferase activity

For exploring functions of understudied protein, we recommend to consider the predicted results from both _CLaf.pt and _CL.pt parameters.
When there are no functions predicted under the probability threshold 0.5, you can set $prob lower to 0.4, 0.3 or even 0.2, and the predicted results still have reference value.

cd data

Our data set can be downloaded from here.

unzip processed.zip

The dataset related files will be under data/processed. Files with prefix of AF2 belong to AFch dataset, others belong to PDBch dataset. Files with suffix of pdbch record the PDBid or uniprot accession of each protein, and files with suffix of graph contain the graph we constructed for each protein.

AF2test_graph.pt  AF2train_graph.pt  AF2val_graph.pt  test_graph.pt  train_graph.pt  val_graph.pt
AF2test_pdbch.pt  AF2train_pdbch.pt  AF2val_pdbch.pt  test_pdbch.pt  train_pdbch.pt  val_pdbch.pt

python train.py --device 0
                --task bp 
                --batch_size 64 
                --suffix CLaf
                --contrast True
                --AF2model True   

$task can be among the three GO-term task -- [bp, mf, cc].
$suffix is the suffix of the model weight file that will be saved.
$contrast is whether to use contrastive learning.
$AF2model is whether to add AFch training set for training.

The *graph.pt file contain the list of protein graphs, the way to build the graph can be seen from predictor.py.
Each graph is built by Pytorch Geometric, and each graph has three attributes.
graph.edge_index \in [2, protein_len] is edge index of residue pairs whose Ca are within 10 angstroms.
graph.native_x is the one-hot embedding for each residue type.
graph.x is the ESM-1b language embedding for each sequences.

graph_data.py is the script to load the data. If you want to train a new model, you can change the self.graph_list and self.y_true variable.