Issue 1, 2021

DeepSIBA: chemical structure-based inference of biological alterations using deep learning

Abstract

Predicting whether a chemical structure leads to a desired or adverse biological effect can have a significant impact for in silico drug discovery. In this study, we developed a deep learning model where compound structures are represented as graphs and then linked to their biological footprint. To make this complex problem computationally tractable, compound differences were mapped to biological effect alterations using Siamese Graph Convolutional Neural Networks. The proposed model was able to encode molecular graph pairs and identify structurally dissimilar compounds that affect similar biological processes with high precision. Additionally, by utilizing deep ensembles to estimate uncertainty, we were able to provide reliable and accurate predictions for chemical structures that are very different from the ones used during training. Finally, we present a novel inference approach, where the trained models are used to estimate the signaling pathway signature of a compound perturbation, using only its chemical structure as input, and subsequently identify which substructures influenced the predicted pathways. As a use case, this approach was used to infer important substructures and affected signaling pathways of FDA-approved anticancer drugs.

Graphical abstract: DeepSIBA: chemical structure-based inference of biological alterations using deep learning

Supplementary files

Article information

Article type
Research Article
Submitted
23 Sep 2020
Accepted
09 Nov 2020
First published
09 Nov 2020
This article is Open Access
Creative Commons BY license

Mol. Omics, 2021,17, 108-120

DeepSIBA: chemical structure-based inference of biological alterations using deep learning

C. Fotis, N. Meimetis, A. Sardis and L. G. Alexopoulos, Mol. Omics, 2021, 17, 108 DOI: 10.1039/D0MO00129E

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