scBPGRN: Integrating single-cell multi-omics data to construct gene regulatory networks based on BP neural network

被引:6
作者
Xuan, Chenxu [1 ]
Wang, Yan [1 ]
Zhang, Bai [1 ]
Wu, Hanwen [1 ]
Ding, Tao [2 ]
Gao, Jie [1 ]
机构
[1] Jiangnan Univ, Sch Sci, Wuxi 214122, Jiangsu, Peoples R China
[2] Newcastle Univ, Sch Math Stat & Phys, Newcastle Upon Tyne NE1 7RU, England
基金
中国国家自然科学基金;
关键词
Single-cell multi-omics; Gene regulatory network; BP neural network; Biweight extreme correlation coefficient; Generalized weight; Node strength; TUMOR-SUPPRESSOR; CANCER; HETEROGENEITY;
D O I
10.1016/j.compbiomed.2022.106249
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
The deterioration and metastasis of cancer involve various aspects of genomic changes, including genomic DNA changes, epigenetic modifications, gene expression, and other complex interactions. Therefore, integrating single-cell multi-omics data to construct gene regulatory networks containing more omics information is of great significance for understanding the pathogenesis of cancer. In this article, an algorithm integrating single-cell RNA sequencing data and DNA methylation data to construct a gene regulatory network based on the back-propagation (BP) neural network (scBPGRN) is proposed. This algorithm uses biweight extreme correlation coefficients to measure the correlation between factors and uses neural networks to calculate generalized weights to construct gene regulation networks. Finally, the node strength is calculated to identify the genes associated with cancer. We apply the scBPGRN algorithm to hepatocellular carcinoma (HCC) data. We construct a regulatory network and identify top-ranked genes, such as MYCBP, KLHL35, PRKCZ, and SERPINA6, as the key HCC-related genes. We analyze the top 100 genes, and the HCC-related genes are concentrated in the top 20. In addition, the single cell data is found to consist of two subpopulations. We also apply scBPGRN to two subpopulations. We analyze the top 50 genes in them, and the HCC-related genes are concentrated in the top 20. The consequences of functional enrichment analysis indicate that the gene regulatory network we have constructed is valid. Our results have been verified in several pieces of literature. This study provides a reference for the integration of single-cell multi-omics data to construct gene regulatory networks.
引用
收藏
页数:11
相关论文
共 46 条
[1]  
Bolboaca S-D, 2006, Leonardo J Sci, V5, P179
[2]   Functional role of SGK3 in PI3K/Pten driven liver tumor development [J].
Cao, Hui ;
Xu, Zhong ;
Wang, Jingxiao ;
Cigliano, Antonio ;
Pilo, Maria G. ;
Ribback, Silvia ;
Zhang, Shu ;
Qiao, Yu ;
Che, Li ;
Pascale, Rosa M. ;
Calvisi, Diego F. ;
Chen, Xin .
BMC CANCER, 2019, 19 (1)
[3]   PFBNet: a priori-fused boosting method for gene regulatory network inference [J].
Che, Dandan ;
Guo, Shun ;
Jiang, Qingshan ;
Chen, Lifei .
BMC BIOINFORMATICS, 2020, 21 (01)
[4]   Hepatic cyclooxygenase-2 overexpression induced spontaneous hepatocellular carcinoma formation in mice [J].
Chen, H. ;
Cai, W. ;
Chu, E. S. H. ;
Tang, J. ;
Wong, C-C ;
Wong, S. H. ;
Sun, W. ;
Liang, Q. ;
Fang, J. ;
Sun, Z. ;
Yu, J. .
ONCOGENE, 2017, 36 (31) :4415-4426
[5]   The Impact of IL28B Genotype and Liver Fibrosis on the Hepatic Expression of IP10, IFI27, ISG15, and MX1 and Their Association with Treatment Outcomes in Patients with Chronic Hepatitis C [J].
Domagalski, Krzysztof ;
Pawlowska, Malgorzata ;
Kozielewicz, Dorota ;
Dybowska, Dorota ;
Tretyn, Andrzej ;
Halota, Waldemar .
PLOS ONE, 2015, 10 (06)
[6]   RAMP3 is a prognostic indicator of liver cancer and might reduce the adverse effect of TP53 mutation on survival [J].
Fang, Aiping ;
Zhou, Shijie ;
Su, Xiaolan ;
Liu, Chuang ;
Chen, Xiaoxin ;
Wan, Yang ;
Lei, Xiaohong ;
Xie, Linshen ;
Jia, Yiping ;
Wang, Wenzhi ;
Yang, Luo ;
Song, Xuejiao ;
Yao, Yuqin .
FUTURE ONCOLOGY, 2018, 14 (25) :2615-2625
[7]   DKK1 promotes hepatocellular carcinoma inflammation, migration and invasion: Implication of TGF-β1 [J].
Fezza, Maha ;
Moussa, Mayssam ;
Aoun, Rita ;
Haber, Rita ;
Hilal, George .
PLOS ONE, 2019, 14 (09)
[8]   Optimization of metabolomic data processing using NOREVA [J].
Fu, Jianbo ;
Zhang, Ying ;
Wang, Yunxia ;
Zhang, Hongning ;
Liu, Jin ;
Tang, Jing ;
Yang, Qingxia ;
Sun, Huaicheng ;
Qiu, Wenqi ;
Ma, Yinghui ;
Li, Zhaorong ;
Zheng, Mingyue ;
Zhu, Feng .
NATURE PROTOCOLS, 2022, 17 (01) :129-151
[9]   miR-4324-RACGAP1-STAT3-ESR1 feedback loop inhibits proliferation and metastasis of bladder cancer [J].
Ge, Qiangqiang ;
Lu, Mengxin ;
Ju, Lingao ;
Qian, Kaiyu ;
Wang, Gang ;
Wu, Chin-Lee ;
Liu, Xuefeng ;
Xiao, Yu ;
Wang, Xinghuan .
INTERNATIONAL JOURNAL OF CANCER, 2019, 144 (12) :3043-3055
[10]   Single-cell triple omics sequencing reveals genetic, epigenetic, and transcriptomic heterogeneity in hepatocellular carcinomas [J].
Hou, Yu ;
Guo, Huahu ;
Cao, Chen ;
Li, Xianlong ;
Hu, Boqiang ;
Zhu, Ping ;
Wu, Xinglong ;
Wen, Lu ;
Tang, Fuchou ;
Huang, Yanyi ;
Peng, Jirun .
CELL RESEARCH, 2016, 26 (03) :304-319