Drug repurposing for non-small cell lung cancer by predicting drug response using pathway-level graph convolutional network.

I T Anjusha, K A Abdul Nazeer, N Saleena
Author Information
  1. I T Anjusha: Department of Computer Science and Engineering, National Institute of Technology Calicut, Kozhikode, India. ORCID
  2. K A Abdul Nazeer: Department of Computer Science and Engineering, National Institute of Technology Calicut, Kozhikode, India. ORCID
  3. N Saleena: Department of Computer Science and Engineering, National Institute of Technology Calicut, Kozhikode, India. ORCID

Abstract

Drug repurposing is the process of identifying new clinical indications for an existing drug. Some of the recent studies utilized drug response prediction models to identify drugs that can be repurposed. By representing cell-line features as a pathway-pathway interaction network, we can better understand the connections between cellular processes and drug response mechanisms. Existing deep learning models for drug response prediction do not integrate known biological pathway-pathway interactions into the model. This paper presents a drug response prediction model that applies a graph convolution operation on a pathway-pathway interaction network to represent features of cancer cell-lines effectively. The model is used to identify potential drug repurposing candidates for Non-Small Cell Lung Cancer (NSCLC). Experiment results show that the inclusion of graph convolutional model applied on a pathway-pathway interaction network makes the proposed model more effective in predicting drug response than the state-of-the-art methods. Specifically, the model has shown better performance in terms of Root Mean Squared Error, Coefficient of Determination, and Pearson's Correlation Coefficient when applied to the GDSC1000 dataset. Also, most of the drugs that the model predicted as top candidates for NSCLC treatment are either undergoing clinical studies or have some evidence in the PubMed literature database.

Keywords

MeSH Term

Carcinoma, Non-Small-Cell Lung
Drug Repositioning
Humans
Lung Neoplasms
Computational Biology
Antineoplastic Agents
Cell Line, Tumor
Deep Learning
Neural Networks, Computer

Chemicals

Antineoplastic Agents

Word Cloud

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