This work is published in Protein Engineering Design & Selection (https://doi.org/10.1093/protein/gzz031).

These instructions will get you a copy of the project up and running on your local machine for development and testing purposes.

The tool was developped based on the following dependencies:

1. PyTorch (1.1 or greater).
2. NumPy (1.16 or greater).
3. tqdm (4.31 or greater).

Please note that the dependencies may require Python 3.6 or greater. It is recommended to install and maintain all packages using conda or pip. For installation of GPU accelerated PyTorch, additional effort may be required. Please check the official websites of PyTorch and CUDA for detailed instructions.

This is a lightweight project targeting the problem related to quantifying the nativeness of antibody sequences and therefore, no sophisticated installation routine is required. All you need is to place it into your project repository and import at need. If you want to put it somewhere else, please check out importlib.util module for more flexible import capability.

These instructions will help you to properly configure and use the tool either through function-call or command-line. For detailed usage of the parameters, you may refer to Documentation section.

All antibody protein sequences must be stored in plain-text format. A sequence consists of 20 amino acid symbol letters along with "-" to indicate gap, and sequences are delimited by one single line-break. Please do not include spaces or extra line-breaks. You can find sample data files under <project_root>/data/sample/

Here we provide an example:

-QVQLVQS-GAEVKKPGSSVKVSCTTSG-GTFSS-----FVINWMRQAPGQGLGWRGGIMPV---
-EVQLLES-GGGLVQPGGSLRLSCAGSG-FTFSS-----YAMSWVRQTPGKGLEWVSVISGS---
-QVQLVES-GGGVVQSGRSLRLSCAASG-FTFRS-----HAIHWVGQAPGKGLEGVGVMSHD---
-QVHLVQS-GAEVHKPGASLRISCKASG-YTFPN-----FFLHWVRQAPGQGLEWMGIINPI---
-QVQLQES-GPGLMKPSGTLSLTCDVSG-ASISN----TNWWGWVRQPPGLGLEWIGEIHH----

To initialize model:

from ablstm import ModelLSTM
model = ModelLSTM(embedding_dim=64, hidden_dim=64, device='cpu', gapped=True, fixed_len=True)

To fit model (without saving):

trn_fn = './data/sample/human_train.txt'
vld_fn = './data/sample/human_val.txt'
model.fit(trn_fn=trn_fn, vld_fn=vld_fn, n_epoch=10, trn_batch_size=128, vld_batch_size=512, lr=.002, save_fp=None)

To score sequences:

tst_fn = './data/sample/human_test.txt'
tst_scores = model.eval(fn=tst_fn, batch_size=512)

To save and load model:

model.save(fn='./saved_models/tmp/model_tmp.npy')
model_loaded = ModelLSTM()
model_loaded.load(fn='./saved_models/tmp/model_tmp.npy')

Since the neural network may have numerous parameters to configure, it may appear excessively verbose if we pass all of them by commands. Most of the model parameters, therefore, are stored within <project_root>/ablstm.config in XML format. The structure and the tag names exactly follow their corresponding Python class definition.

Here is the default configuration XML file.

<?xml version="1.0"?>
<ablstm>
    <__init__>
        <embedding_dim>64</embedding_dim>
        <hidden_dim>64</hidden_dim>
        <gapped>True</gapped>
        <fixed_len>True</fixed_len>
    </__init__>
    <fit>
        <n_epoch>8</n_epoch>
        <trn_batch_size>128</trn_batch_size>
        <vld_batch_size>512</vld_batch_size>
        <lr>0.002</lr>
    </fit>
    <eval>
        <batch_size>512</batch_size>
    </eval>
</ablstm>

To start fresh training:

python ablstm.py fit ./data/sample/human_train.txt ./data/sample/human_val.txt ./saved_models/tmp

To load a saved model and resume training:

python ablstm.py fit ./data/sample/human_train.txt ./data/sample/human_val.txt ./saved_models/tmp -l ./saved_models/tmp/model_tmp.npy

To use a configuration file other than <project_root>/ablstm.config:

python ablstm.py fit ./data/sample/human_train.txt ./data/sample/human_val.txt ./saved_models/tmp -c ./ablstm_new.config

To evaluate sequence scores using a saved model:

python ablstm.py eval ./data/sample/human_test.txt ./saved_models/tmp/model_tmp.npy ./results/result_human_test.txt

Initializes an LSTM model with the given parameters.

Parameters:

1. embedding_dim: int, default is 64

Embedding layer dimensions.

2. hidden_dim: int, default is 64

Hiddden layer dimensions.

3. device: str, default is 'cpu'

Device that the model will be mounted on. If GPU is available and CUDA is properly installed, you can assign "cuda:0" (or "cuda:<DEVICE_INDEX>" if you have more GPUs) that will greatly accelerate training and evaluation process.

4. gapped: bool, default is True

Indicate whether the input sequences contain gaps. A gap is always denoted as "-".

5. fixed_len: bool, default is True

Indicate whether the input sequences share equal length. It can be set False without any issue in all circumstances, but when the sequence lengths are assured to be the same, setting it True will help speed up the computation significantly.

Fit the model using the given training and validation data.

Parameters:

1. trn_fn: str

Data file for training.

2. vld_fn: str

Data file for validation.

3. n_epoch: int, default is 10

Number of epochs.

4. trn_batch_size: str, default is 128

Batch size during training. -1 means whole batch.

5. vld_batch_size: str, default is 512

Batch size during validation. -1 means whole batch.

6. lr: float, default is 0.002

Learning rate. The fitting process uses Adam algorithm for optimization.

7. save_fp: str, optional, default is None

Path to save models. None or "" means training without saving. If a valid path is given, model will be saved under the path after each epoch as long as the validation performance is better than the past.

Scores the given sequences.

Parameters:

1. fn: str

Data file for evaluation.

2. batch_size: int, default is 512

Batch size. -1 means whole batch.

Returns:

1. scores: NumPy ndarray

1-D NumPy array consists of all sequences' scores. Order is preserved.

Assign device.

Parameters:

1. device: str, default is "cpu"

Device to mount.

Save model.

Parameters:

1. fn: str

Save file name.

Load model from the given file. Please note that when load() method is invoked, all parameters will be overloaded except device. You may call ablstm.ModelLSTM.to() method to switch among different devices.

Parameters:

1. fn: str

Model file name.

Returns:

1. model: ablstm.ModelLSTM

Loaded model.

usage: ablstm.py fit [-h] [-l L] [-c C] [-d D] TRN_FN VLD_FN SAVE_FP

positional arguments:
  TRN_FN      training data file
  VLD_FN      validation data file
  SAVE_FP     model save path

optional arguments:
  -h, --help  show this help message and exit
  -l L        model file to load (default: "")
  -c C        configuration XML file (default: "./ablstm.config")
  -d D        device (default: "cpu")

usage: ablstm.py eval [-h] [-c C] [-d D] TST_FN MDL_FN SCR_FN

positional arguments:
  TST_FN      evaluation data file
  MDL_FN      model file to load
  SCR_FN      file to save scores

optional arguments:
  -h, --help  show this help message and exit
  -c C        configuration XML file (default: "./ablstm.config")
  -d D        device (default: "cpu")

• Chonghua Xue, [email protected] - Kolachalama laboratory, Boston University School of Medicine

• Visterra Inc., Waltham, MA, USA