scholarly journals DriverSubNet: A Novel Algorithm for Identifying Cancer Driver Genes by Subnetwork Enrichment Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Di Zhang ◽  
Yannan Bin

Identification of driver genes from mass non-functional passenger genes in cancers is still a critical challenge. Here, an effective and no parameter algorithm, named DriverSubNet, is presented for detecting driver genes by effectively mining the mutation and gene expression information based on subnetwork enrichment analysis. Compared with the existing classic methods, DriverSubNet can rank driver genes and filter out passenger genes more efficiently in terms of precision, recall, and F1 score, as indicated by the analysis of four cancer datasets. The method recovered about 50% more known cancer driver genes in the top 100 detected genes than those found in other algorithms. Intriguingly, DriverSubNet was able to find these unknown cancer driver genes which could act as potential therapeutic targets and useful prognostic biomarkers for cancer patients. Therefore, DriverSubNet may act as a useful tool for the identification of driver genes by subnetwork enrichment analysis.

2016 ◽  
Vol 12 (9) ◽  
pp. 2921-2931 ◽  
Author(s):  
Kai Shi ◽  
Lin Gao ◽  
Bingbo Wang

An integrated network-based approach is proposed to nominate driver genes. It is composed of two steps including a network diffusion step and an aggregated ranking step, which fuses the correlation between the gene mutations and gene expression, the relationship between the mutated genes and the heterogeneous characteristic of the patient mutation.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Ege Ülgen ◽  
O. Uğur Sezerman

Abstract Background Cancer develops due to “driver” alterations. Numerous approaches exist for predicting cancer drivers from cohort-scale genomics data. However, methods for personalized analysis of driver genes are underdeveloped. In this study, we developed a novel personalized/batch analysis approach for driver gene prioritization utilizing somatic genomics data, called driveR. Results Combining genomics information and prior biological knowledge, driveR accurately prioritizes cancer driver genes via a multi-task learning model. Testing on 28 different datasets, this study demonstrates that driveR performs adequately, achieving a median AUC of 0.684 (range 0.651–0.861) on the 28 batch analysis test datasets, and a median AUC of 0.773 (range 0–1) on the 5157 personalized analysis test samples. Moreover, it outperforms existing approaches, achieving a significantly higher median AUC than all of MutSigCV (Wilcoxon rank-sum test p < 0.001), DriverNet (p < 0.001), OncodriveFML (p < 0.001) and MutPanning (p < 0.001) on batch analysis test datasets, and a significantly higher median AUC than DawnRank (p < 0.001) and PRODIGY (p < 0.001) on personalized analysis datasets. Conclusions This study demonstrates that the proposed method is an accurate and easy-to-utilize approach for prioritizing driver genes in cancer genomes in personalized or batch analyses. driveR is available on CRAN: https://cran.r-project.org/package=driveR.


EBioMedicine ◽  
2018 ◽  
Vol 27 ◽  
pp. 156-166 ◽  
Author(s):  
Magali Champion ◽  
Kevin Brennan ◽  
Tom Croonenborghs ◽  
Andrew J. Gentles ◽  
Nathalie Pochet ◽  
...  

Hereditas ◽  
2021 ◽  
Vol 158 (1) ◽  
Author(s):  
Yun Tang ◽  
Xiaobo Yang ◽  
Huaqing Shu ◽  
Yuan Yu ◽  
Shangwen Pan ◽  
...  

Abstract Background Sepsis and septic shock are life-threatening diseases with high mortality rate in intensive care unit (ICU). Acute kidney injury (AKI) is a common complication of sepsis, and its occurrence is a poor prognostic sign to septic patients. We analyzed co-differentially expressed genes (co-DEGs) to explore relationships between septic shock and AKI and reveal potential biomarkers and therapeutic targets of septic-shock-associated AKI (SSAKI). Methods Two gene expression datasets (GSE30718 and GSE57065) were downloaded from the Gene Expression Omnibus (GEO). The GSE57065 dataset included 28 septic shock patients and 25 healthy volunteers and blood samples were collected within 0.5, 24 and 48 h after shock. Specimens of GSE30718 were collected from 26 patients with AKI and 11 control patents. AKI-DEGs and septic-shock-DEGs were identified using the two datasets. Subsequently, Gene Ontology (GO) functional analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein-protein interaction (PPI) network analysis were performed to elucidate molecular mechanisms of DEGs. We also evaluated co-DEGs and corresponding predicted miRNAs involved in septic shock and AKI. Results We identified 62 DEGs in AKI specimens and 888, 870, and 717 DEGs in septic shock blood samples within 0.5, 24 and 48 h, respectively. The hub genes of EGF and OLFM4 may be involved in AKI and QPCT, CKAP4, PRKCQ, PLAC8, PRC1, BCL9L, ATP11B, KLHL2, LDLRAP1, NDUFAF1, IFIT2, CSF1R, HGF, NRN1, GZMB, and STAT4 may be associated with septic shock. Besides, co-DEGs of VMP1, SLPI, PTX3, TIMP1, OLFM4, LCN2, and S100A9 coupled with corresponding predicted miRNAs, especially miR-29b-3p, miR-152-3p, and miR-223-3p may be regarded as promising targets for the diagnosis and treatment of SSAKI in the future. Conclusions Septic shock and AKI are related and VMP1, SLPI, PTX3, TIMP1, OLFM4, LCN2, and S100A9 genes are significantly associated with novel biomarkers involved in the occurrence and development of SSAKI.


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