# MVGAE: A Multi-View Graph Auto-Encoder Model for Drug Prediction of Non-Small Cell Lung Cancer Based on Synthetic Lethality

**Authors:** Shaobo Hu, Runsheng Jiang, Ning Zhao

PMC · DOI: 10.3390/cimb48030269 · 2026-03-03

## TL;DR

This study uses a new computational model to predict key genes and drugs for treating non-small cell lung cancer.

## Contribution

The study introduces MVGAE, a novel multi-view graph auto-encoder model for drug prediction based on synthetic lethality in NSCLC.

## Key findings

- Predicted seven potential driver genes associated with NSCLC using the NIAPU model.
- Identified nine genes with synthetic lethality interactions as candidate therapeutic targets.
- Predicted corresponding targeted drugs using the MVGAE model, including PAZOPANIB.

## Abstract

What are the main findings?
This study predicts nine key therapeutic target genes in non-small cell lung cancer (NSCLC) and identified their corresponding potential targeted drugs.

This study predicts nine key therapeutic target genes in non-small cell lung cancer (NSCLC) and identified their corresponding potential targeted drugs.

What are the implications of the main findings?
2.Provides experimentally testable target and drug candidates for NSCLC therapy.3.Establishes an extensible computational pipeline for multi-omics target discovery.

Provides experimentally testable target and drug candidates for NSCLC therapy.

Establishes an extensible computational pipeline for multi-omics target discovery.

Identifying therapeutic target genes and their corresponding targeted drugs is of significant importance for the treatment of non-small cell lung cancer (NSCLC). This study proposes a multi-view graph auto-encoder model (MVGAE), which, together with the network-informed adaptive positive-unlabeled (NIAPU) and synthetic lethality multi-view graph auto-encoder (SLMGAE) model, constitutes an integrated computational framework. The framework integrates multi-source biological network data, including protein–protein interaction networks, disease-gene association information, and gene-drug bipartite graphs, for data mining. Through systematic analysis and computational screening, we ultimately predicted seven potential driver genes associated with NSCLC using the NIAPU model. The SLMGAE model predicted nine genes with synthetic lethality (SL) interactions to these driver genes as candidate therapeutic targets. Based on these SL targets, the MVGAE model further predicted corresponding targeted drugs. Notably, among the prioritized targets, existing studies indicate that ATR and RAD51 exhibit conditional SL effects in the context of functional impairment. Furthermore, several of the predicted candidate drugs (such as PAZOPANIB) have been previously reported to play a positive role in NSCLC treatment. This study highlights MVGAE as a novel computational framework for drug repurposing and demonstrates how its integration with complementary models can effectively prioritize potential therapeutic targets and candidate drugs, providing a robust computational basis for precision treatment strategies.

## Linked entities

- **Genes:** ATR (ATR checkpoint kinase) [NCBI Gene 545], RAD51 (RAD51 recombinase) [NCBI Gene 5888]
- **Chemicals:** PAZOPANIB (PubChem CID 10113978)
- **Diseases:** non-small cell lung cancer (MONDO:0005233), NSCLC (MONDO:0005233)

## Full-text entities

- **Genes:** PTPMT1 (protein tyrosine phosphatase mitochondrial 1) [NCBI Gene 114971] {aka DUSP23, MOSP, NEDAXBA, PLIP, PNAS-129}, CFLAR (CASP8 and FADD like apoptosis regulator) [NCBI Gene 8837] {aka CASH, CASP8AP1, CLARP, Casper, FLAME, FLAME-1}, CCND1 (cyclin D1) [NCBI Gene 595] {aka BCL1, D11S287E, PRAD1, U21B31}, RAD50 (RAD50 double strand break repair protein) [NCBI Gene 10111] {aka NBSLD, RAD502, hRad50}, SMARCA4 (SWI/SNF related BAF chromatin remodeling complex subunit ATPase 4) [NCBI Gene 6597] {aka BAF190, BAF190A, BRG1, CSS4, MRD16, OTSC12}, PGR (progesterone receptor) [NCBI Gene 5241] {aka NR3C3, PR}, DDB1 (damage specific DNA binding protein 1) [NCBI Gene 1642] {aka DDBA, UV-DDB1, WHIKERS, XAP1, XPCE, XPE}, FBXW7 (F-box and WD repeat domain containing 7) [NCBI Gene 55294] {aka AGO, CDC4, DEDHIL, FBW6, FBW7, FBX30}, RAD51 (RAD51 recombinase) [NCBI Gene 5888] {aka BRCC5, FANCR, HRAD51, HsRad51, HsT16930, MRMV2}, CYCS (cytochrome c, somatic) [NCBI Gene 54205] {aka CYC, HCS, THC4}, IL6ST (interleukin 6 cytokine family signal transducer) [NCBI Gene 3572] {aka CD130, CDW130, GP130, HIES4, HIES4A, HIES4B}, TSC1 (TSC complex subunit 1) [NCBI Gene 7248] {aka LAM, TSC}, TTN (titin) [NCBI Gene 7273] {aka CMD1G, CMH9, CMPD4, CMYO5, CMYP5, EOMFC}, BRCA1 (BRCA1 DNA repair associated) [NCBI Gene 672] {aka BRCAI, BRCC1, BROVCA1, FANCS, IRIS, PNCA4}, CDK1 (cyclin dependent kinase 1) [NCBI Gene 983] {aka CDC2, CDC28A, P34CDC2}, CHEK1 (checkpoint kinase 1) [NCBI Gene 1111] {aka CHK1, OZEMA21}, JUN (Jun proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 3725] {aka AP-1, AP1, c-Jun, cJUN, p39}, ATR (ATR checkpoint kinase) [NCBI Gene 545] {aka FCTCS, FRP1, MEC1, SCKL, SCKL1}, C1QTNF2 (C1q and TNF related 2) [NCBI Gene 114898] {aka CTRP2, zacrp2}, BRCA2 (BRCA2 DNA repair associated) [NCBI Gene 675] {aka BRCC2, BROVCA2, FACD, FAD, FAD1, FANCD}, PCNA (proliferating cell nuclear antigen) [NCBI Gene 5111] {aka ATLD2}, TTC41P (tetratricopeptide repeat domain 41, pseudogene) [NCBI Gene 253724] {aka GNN, GNNP}, PARP1 (poly(ADP-ribose) polymerase 1) [NCBI Gene 142] {aka ADPRT, ADPRT 1, ADPRT1, ARTD1, PARP, PARP-1}, CDC20 (cell division cycle 20) [NCBI Gene 991] {aka CDC20A, OOMD14, OZEMA14, bA276H19.3, p55CDC}
- **Diseases:** breast or colorectal cancer (MESH:D001943), erythema nodosum leprosum (MESH:D004893), LUSC (MESH:D002294), SL (OMIM:146820), LUAD (MESH:D000077192), Cancer (MESH:D009369), NSCLC (MESH:D002289), cytotoxicity (MESH:D064420), ovarian and breast cancers (MESH:D061325), injury to (MESH:D014947), Lung cancer (MESH:D008175)
- **Chemicals:** TANDUTINIB (MESH:C464670), PHA-793887 (MESH:C549971), BORTEZOMIB (MESH:D000069286), PI-103 (MESH:C522973), PAZOPANIB (MESH:C516667), DINACICLIB (MESH:C553669), thalidomide (MESH:D013792), MVGAE (-), hydrogen (MESH:D006859)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

10 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13025638/full.md

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Source: https://tomesphere.com/paper/PMC13025638