Generic placeholder image

Current Gene Therapy

Editor-in-Chief

ISSN (Print): 1566-5232
ISSN (Online): 1875-5631

Research Article

Inferring Cell-type-specific Genes of Lung Cancer Based on Deep Learning

Author(s): Nitao Cheng, Chen Chen, Changsheng Li and Jingyu Huang*

Volume 22, Issue 5, 2022

Published on: 25 May, 2022

Page: [439 - 448] Pages: 10

DOI: 10.2174/1566523222666220324110914

Price: $65

conference banner
Abstract

Background: Lung cancer is cancer with the highest incidence in the world, and there is obvious heterogeneity within its tumor. The emergence of single-cell sequencing technology allows researchers to obtain cell-type-specific expression genes at the single-cell level, thereby obtaining information regarding the cell status and subpopulation distribution, as well as the communication behavior between cells. Many researchers have applied this technology to lung cancer research, but due to the shortcomings of insufficient sequencing depth, only a small part of the gene expression can be detected. Researchers can only roughly compare whether a few thousand genes are significant in different cell types.

Methods: To fully explore the expression of all genes in different cell types, we propose a method to predict cell-type-specific genes. This method infers cell-type-specific genes based on the expression levels of genes in different tissues and cells and gene interactions. At present, biological experiments have discovered a large number of cell-type-specific genes, providing a large number of available samples for the application of deep learning methods.

Results: Therefore, we fused Graph Convolutional Network (GCN) with Convolutional Neural Network( CNN) to build, model, and inferred cell-type-specific genes of lung cancer in 8 cell types.

Conclusion: This method further analyzes and processes single-cell data and provides a new basis for research on heterogeneity in lung cancer tumor, microenvironment, invasion and metastasis, treatment response, drug resistance, etc.

Keywords: Cell-type-specific genes, single-cell sequencing, lung cancer, deep learning, chemotherapy, radiotherapy.

Graphical Abstract

[1]
Peters S, Camidge DR, Shaw AT, et al. ALEX trial investigators. Alectinib versus crizotinib in untreated ALK-positive non–small-cell lung cancer. N Engl J Med 2017; 377(9): 829-38.
[http://dx.doi.org/10.1056/NEJMoa1704795] [PMID: 28586279]
[2]
Douillard JY, Ostoros G, Cobo M, et al. First-line gefitinib in Caucasian EGFR mutation-positive NSCLC patients: A phase-IV, open-label, single-arm study. Br J Cancer 2014; 110(1): 55-62.
[http://dx.doi.org/10.1038/bjc.2013.721] [PMID: 24263064]
[3]
Nam AS, Chaligne R, Landau DA. Integrating genetic and non-genetic determinants of cancer evolution by single-cell multi-omics. Nat Rev Genet 2021; 22(1): 3-18.
[http://dx.doi.org/10.1038/s41576-020-0265-5] [PMID: 32807900]
[4]
Navin N, Kendall J, Troge J, et al. Tumour evolution inferred by single-cell sequencing. Nature 2011; 472(7341): 90-4.
[http://dx.doi.org/10.1038/nature09807] [PMID: 21399628]
[5]
Zhao T, Lyu S, Lu G, et al. SC2disease: A manually curated database of single-cell transcriptome for human diseases. Nucleic Acids Res 2021; 49(D1): D1413-9.
[http://dx.doi.org/10.1093/nar/gkaa838] [PMID: 33010177]
[6]
Sade-Feldman M, Yizhak K, Bjorgaard SL, et al. Defining T cell states associated with response to checkpoint immunotherapy in melanoma. Cell 2018; 175(4): 998-1013.
[PMID: 30388456]
[7]
Casasent AK, Schalck A, Gao R, et al. Multiclonal invasion in breast tumors identified by topographic single cell sequencing. Cell 2018; 172: 205-17.
[http://dx.doi.org/10.1016/j.cell.2017.12.007] [PMID: 29307488]
[8]
Zhang L, Li Z, Skrzypczynska KM, et al. Single-cell analyses inform mechanisms of myeloid-targeted therapies in colon cancer. Cell 2020; 181(2): 442-59.
[http://dx.doi.org/10.1016/j.cell.2020.03.048] [PMID: 32302573]
[9]
Lu T, Yang X, Shi Y, et al. Single-cell transcriptome atlas of lung adenocarcinoma featured with ground glass nodules. Cell Discov 2020; 6(1): 69.
[http://dx.doi.org/10.1038/s41421-020-00200-x] [PMID: 33083004]
[10]
Maynard A, McCoach CE, Rotow JK, et al. Therapy-induced evolution of human lung cancer revealed by single-cell RNA sequencing. Cell 2020; 182: 1232-51.
[http://dx.doi.org/10.1016/j.cell.2020.07.017] [PMID: 32822576]
[11]
Lambrechts D, Wauters E, Boeckx B, et al. Phenotype molding of stromal cells in the lung tumor microenvironment. Nat Med 2018; 24(8): 1277-89.
[http://dx.doi.org/10.1038/s41591-018-0096-5] [PMID: 29988129]
[12]
Kim N, Kim HK, Lee K, et al. Single-cell RNA sequencing demonstrates the molecular and cellular reprogramming of metastatic lung adenocarcinoma. Nat Commun 2020; 11(1): 2285.
[http://dx.doi.org/10.1038/s41467-020-16164-1] [PMID: 32385277]
[13]
Kim K-T, Lee HW, Lee H-O, et al. Single-cell mRNA sequencing identifies subclonal heterogeneity in anti-cancer drug responses of lung adenocarcinoma cells. Genome Biol 2015; 16(1): 127.
[http://dx.doi.org/10.1186/s13059-015-0692-3] [PMID: 26084335]
[14]
Gong W, Kwak I-Y, Pota P, Koyano-Nakagawa N, Garry DJ. DrImpute: Imputing dropout events in single cell RNA sequencing data. BMC Bioinformatics 2018; 19(1): 220.
[http://dx.doi.org/10.1186/s12859-018-2226-y] [PMID: 29884114]
[15]
Qiu P. Embracing the dropouts in single-cell RNA-seq analysis. Nat Commun 2020; 11(1): 1169.
[http://dx.doi.org/10.1038/s41467-020-14976-9] [PMID: 32127540]
[16]
Tracy S, Yuan G-C, Dries R. RESCUE: Imputing dropout events in single-cell RNA-sequencing data. BMC Bioinformatics 2019; 20(1): 388.
[http://dx.doi.org/10.1186/s12859-019-2977-0] [PMID: 31299886]
[17]
Vallejos CA, Risso D, Scialdone A, Dudoit S, Marioni JC. Normalizing single-cell RNA sequencing data: Challenges and opportunities. Nat Methods 2017; 14(6): 565-71.
[http://dx.doi.org/10.1038/nmeth.4292] [PMID: 28504683]
[18]
Zhang X-F, Ou-Yang L, Yang S, Zhao X-M, Hu X, Yan H. EnImpute: Imputing dropout events in single-cell RNA-sequencing data via ensemble learning. Bioinformatics 2019; 35(22): 4827-9.
[http://dx.doi.org/10.1093/bioinformatics/btz435] [PMID: 31125056]
[19]
Ye P, Ye W, Ye C, et al. scHinter: Imputing dropout events for single-cell RNA-seq data with limited sample size. Bioinformatics 2020; 36(3): 789-97.
[PMID: 31392316]
[20]
Stegle O, Teichmann SA, Marioni JC. Computational and analytical challenges in single-cell transcriptomics. Nat Rev Genet 2015; 16(3): 133-45.
[http://dx.doi.org/10.1038/nrg3833] [PMID: 25628217]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy