Graph neural networks are promising for phenotypic virtual screening on cancer cell lines
File(s)
Published version
Author(s)
Vishwakarma, Sachin
Hernandez-Hernandez, Saiveth
Ballester, Pedro J
Type
Journal Article
Abstract
Artificial intelligence is increasingly driving early drug design, offering novel approaches to virtual screening. Phenotypic virtual screening (PVS) aims to predict how cancer cell lines respond to different compounds by focusing on observable characteristics rather than specific molecular targets. Some studies have suggested that deep learning may not be the best approach for PVS. However, these studies are limited by the small number of tested molecules as well as not employing suitable performance metrics and dissimilar-molecules splits better mimicking the challenging chemical diversity of real-world screening libraries. Here we prepared 60 datasets, each containing approximately 30 000–50 000 molecules tested for their growth inhibitory activities on one of the NCI-60 cancer cell lines. We conducted multiple performance evaluations of each of the five machine learning algorithms for PVS on these 60 problem instances. To provide even a more comprehensive evaluation, we used two model validation types: the random split and the dissimilar-molecules split. Overall, about 14 440 training runs aczross datasets were carried out per algorithm. The models were primarily evaluated using hit rate, a more suitable metric in VS contexts. The results show that all models are more challenged by test molecules that are substantially different from those in the training data. In both validation types, the D-MPNN algorithm, a graph-based deep neural network, was found to be the most suitable for building predictive models for this PVS problem.
Date Issued
2024
Date Acceptance
2024-09-02
Citation
Biology Methods & Protocols, 2024, 9 (1)
ISSN
2396-8923
Publisher
Oxford University Press
Journal / Book Title
Biology Methods & Protocols
Volume
9
Issue
1
Copyright Statement
© The Author(s) 2024. Published by Oxford University Press.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
License URL
Identifier
https://academic.oup.com/biomethods/article/9/1/bpae065/7748407
Publication Status
Published
Article Number
bpae065
Date Publish Online
2024-09-03