morgen01/binn

Generating biologically informed neural networks

Biologically Informed Neural Network (BINN)

BINN documentation is avaiable here.

The BINN-package allows you to create a sparse neural network from a pathway and input file. The examples presented in docs use the Reactome pathway database and a proteomic dataset to generate the neural network. It also allows you to train and interpret the network using SHAP. Plotting functions are also available for generating sankey plots. The article presenting the BINN can currently be found here.

Have a look at the poster_ndpia.ipynb for an example of a complete quick and easy BINN analysis.

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Installation

BINN can be installed via pip

pip install binn

The package can also be built from source and installed with git.

git clone [email protected]:InfectionMedicineProteomics/BINN.git
pip install -e BINN/

Usage

First, a network is created. This is the network that will be used to create the sparse BINN.

from binn import BINN, Network
import pandas as pd

input_data = pd.read_csv("../data/test_qm.tsv", sep="\t")
translation = pd.read_csv("../data/translation.tsv", sep="\t")
pathways = pd.read_csv("../data/pathways.tsv", sep="\t")

network = Network(
    input_data=input_data,
    pathways=pathways,
    mapping=translation,
    verbose=True
)

The BINN can thereafter be generated using the network:

binn = BINN(
    pathways=network,
    n_layers=4,
    dropout=0.2,
    validate=False,
)

An sklearn wrapper is also available:

from binn import BINNClassifier

binn = BINNClassifier(
    pathways=network,
    n_layers=4,
    dropout=0.2,
    validate=True,
    epochs=10,
    threads=10,
)

This generates the Pytorch sequential model:

Sequential(
  (Layer_0): Linear(in_features=446, out_features=953, bias=True)
  (BatchNorm_0): BatchNorm1d(953, eps=1e-05, momentum=0.1, affine=True, track_running_stats=True)
  (Dropout_0): Dropout(p=0.2, inplace=False)
  (Tanh 0): Tanh()
  (Layer_1): Linear(in_features=953, out_features=455, bias=True)
  (BatchNorm_1): BatchNorm1d(455, eps=1e-05, momentum=0.1, affine=True, track_running_stats=True)
  (Dropout_1): Dropout(p=0.2, inplace=False)
  (Tanh 1): Tanh()
  (Layer_2): Linear(in_features=455, out_features=162, bias=True)
  (BatchNorm_2): BatchNorm1d(162, eps=1e-05, momentum=0.1, affine=True, track_running_stats=True)
  (Dropout_2): Dropout(p=0.2, inplace=False)
  (Tanh 2): Tanh()
  (Layer_3): Linear(in_features=162, out_features=28, bias=True)
  (BatchNorm_3): BatchNorm1d(28, eps=1e-05, momentum=0.1, affine=True, track_running_stats=True)
  (Dropout_3): Dropout(p=0.2, inplace=False)
  (Tanh 3): Tanh()
  (Output layer): Linear(in_features=28, out_features=2, bias=True)
)

Example input

Data - this file should contain a column with the feature names (quantmatrix or some matrix containing input column - in this case "Protein"). These need to map to the input layer of the BINN, either directly or by providing a translation file.

Protein
P00746
P00746
P04004
P27348
P02751
...

Pathways file - this file should contain the mapping used to create the connectivity in the hidden layers.

target	source
R-BTA-109581	R-BTA-109606
R-BTA-109581	R-BTA-169911
R-BTA-109581	R-BTA-5357769
R-BTA-109581	R-BTA-75153
R-BTA-109582	R-BTA-140877
...

Translation file - this file is alternative, but is useful if some translation is needed to map the input features to the pathways in the hiddenn layers. In this case, it is used to map proteins (UniProt IDs) to pathways (Reactome IDs).

input	translation
A0A075B6P5	R-HSA-166663
A0A075B6P5	R-HSA-173623
A0A075B6P5	R-HSA-198933
A0A075B6P5	R-HSA-202733
A0A075B6P5	R-HSA-2029481
...

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Plotting

Plotting a subgraph starting from a node generates the plot: A complete sankey may look like this:

Testing

The software has been tested on desktop machines running Windows 10/Linux (Ubuntu). Small networks are not RAM-intensive and all experiments have been run comfortably with 16 GB RAM.

Cite

Please cite:

Hartman, E., Scott, A.M., Karlsson, C. et al. Interpreting biologically informed neural networks for enhanced proteomic biomarker discovery and pathway analysis. Nat Commun 14, 5359 (2023). https://doi.org/10.1038/s41467-023-41146-4

if you use this package.

Contributors

Erik Hartman, infection medicine proteomics, Lund University

Aaron Scott, infection medicine proteomics, Lund University

Contact

Erik Hartman - [email protected]