A graphSAGE discovers synergistic combinations of Gefitinib, paclitaxel, and Icotinib for Lung adenocarcinoma management by targeting human genes and proteins: the RAIN protocol

BackgroundAdenocarcinoma of the lung is the most common type of lung cancer, and it is characterized by distinct cellular and molecular features. It occurs when abnormal lung cells multiply out of control and form a tumor in the outer region of the lungs. Adenocarcinoma of the lung is a serious and life-threatening condition that requires effective and timely management to improve the survival and quality of life of the patients. One of the challenges in this cancer treatment is finding the optimal combination of drugs that can target the genes or proteins that are involved in the disease process. MethodIn this article, we propose a novel method to recommend combinations of trending drugs to target its associated proteins/genes, using a Graph Neural Network (GNN) under the RAIN protocol. The RAIN protocol is a three-step framework that consists of: 1) Applying graph neural networks to recommend drug combinations by passing messages between trending drugs for managing disease and genes that act as potential targets for disease; 2) Retrieving relevant articles with clinical trials that include those proposed drugs in previous step using Natural Language Processing (NLP). The search queries include "Adenocarcinoma of the lung", "Gefitinib", "Paclitaxel", "Icotinib" that searched context based in databases using NLP; 3) Analyzing the network meta-analysis to measure the comparative efficacy of the drug combinations. ResultWe applied our method to a dataset of nodes and edges that represent the network, where each node is a drug or a gene, and each edge is a p-value between them. We found that the graph neural network recommends combining Gefitinib, Paclitaxel, and Icotinib as the most effective drug combination to target this cancer associated proteins/genes. We reviewed the clinical trials and expert opinions on these medications and found that they support our claim. The network meta-analysis also confirmed the effectiveness of these drugs on associated genes. ConclusionOur method is a novel and promising approach to recommend trending drugs combination to target cancer associated proteins/genes, using graph neural networks under the RAIN protocol. It can help clinicians and researchers to find the best treatment options for patients, and also provide insights into the underlying mechanisms of the disease. HighlightsO_LIProposing the combination of medicinal compounds together for the treatment of lung adenocarcinoma C_LIO_LIachieved a p-value of 0.002858 between lung adenocarcinoma and targeted proteins/genes C_LIO_LI3-Leveraging GraphSAGE for Suggesting an Optimal Drug Combinations. C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=105 SRC="FIGDIR/small/24304384v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@af030borg.highwire.dtl.DTLVardef@1f0e960org.highwire.dtl.DTLVardef@169d70aorg.highwire.dtl.DTLVardef@1a4eade_HPS_FORMAT_FIGEXP M_FIG C_FIG