Dataset Information

Establishment of a SVM classifier to predict recurrence of ovarian cancer.

ABSTRACT: Gene expression data using retrieved ovarian cancer (OC) samples were used to identify genes of interest and a support vector machine (SVM) classifier was subsequently established to predict the recurrence of OC. Three datasets (GSE17260, GSE44104 and GSE51088) investigating OC gene expression were downloaded from the Gene Expression Omnibus. Differentially expressed genes (DEGs) in samples from patients with non?recurrent and recurrent OC were revealed via a homogeneity test and quality control analysis. A protein?protein interaction (PPI) network was subsequently established for the DEGs using data from Biological General Repository for Interaction Datasets, Human Protein Reference Database and Database of Interacting Proteins. Degrees of interaction and betweenness centrality (BC) scores were calculated for each node in the PPI network. The top 100 genes ranked by BC scores were selected to identify feature genes via recursive feature elimination using the GSE17260 dataset. Following this, a SVM classifier was constructed and further validated using the GSE44104 and GSE51088 datasets and independent gene expression data obtained from the Cancer Genome Atlas (TCGA). A total of 639 DEGs were identified from the three gene expression datasets, and a PPI network including 249 nodes and 354 edges was constructed. A SVM classifier consisting of 39 feature genes (including cullin 3, mouse double minute 2 homolog, aurora kinase A, WW domain containing oxidoreducatase, large tumor suppressor kinase 2, sirtuin 6, staphylococcal nuclease and tudor domain containing 1, leucine rich repeats and immunoglobulin like domains 1 and aurora kinase 1 interacting protein 1) was subsequently constructed. The prediction accuracies of the SVM classifier for GSE17260, GSE44104 and GSE51088 datasets as well as data downloaded from TCGA were revealed to be 92.7, 93.3, 96.6 and 90.4%, respectively. Furthermore, the results of the present study revealed that patients with predicted non?recurrent OC survived significantly longer compared with the patients with predicted recurrent OC (P=6.598x10?6). A SVM classifier consisting of 39 feature genes was established for predicting the recurrence and prognosis of OC. Therefore, the results of the present study suggested that the 39 feature genes may serve important roles in the development of OC and may represent therapeutic biomarkers of OC.

SUBMITTER: Zhou J

PROVIDER: S-EPMC6131358 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Establishment of a SVM classifier to predict recurrence of ovarian cancer.

Zhou Jinting J Li Lin L Wang Liling L Li Xiaofang X Xing Hui H Cheng Li L

Molecular medicine reports 20180808 4

Gene expression data using retrieved ovarian cancer (OC) samples were used to identify genes of interest and a support vector machine (SVM) classifier was subsequently established to predict the recurrence of OC. Three datasets (GSE17260, GSE44104 and GSE51088) investigating OC gene expression were downloaded from the Gene Expression Omnibus. Differentially expressed genes (DEGs) in samples from patients with non‑recurrent and recurrent OC were revealed via a homogeneity test and quality control ...[more]

PMID: 30106117

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Project description:Ovarian cancer (OC) is associated with a poor prognosis due to difficulties in early detection. The aims of the present study were to construct a recurrence risk prediction model and to reveal important OC genes or pathways. RNA sequencing data was obtained for 307 OC samples, and the corresponding clinical data were downloaded from The Cancer Genome Atlas database. Additionally, two validation datasets, GSE44104 (20 recurrent and 40 non?recurrent OC samples) and GSE49997 (204 OC samples), were obtained from the Gene Expression Omnibus database. Differentially expressed genes were screened using the differential expression via distance synthesis algorithm, followed by gene ontology enrichment analysis and weighted gene coexpression network analysis (WGCNA). Furthermore, subnetwork analysis was conducted for the protein?protein interaction (PPI) network using the BioNet package. Finally, a random forest classifier was constructed based on the subnetwork nodes, and its reliability was validated using the GSE44104 and GSE49997 validation datasets. A total of 44 upregulated and 117 downregulated genes were identified in the recurrent samples. Enrichment analysis indicated that cytochrome P450 family 17 subfamily A member 1 (CYP17A1) was associated with 'positive regulation of steroid hormone biosynthetic processes'. WGCNA identified turquoise and grey modules that were significantly correlated with status and prognosis. A significant PPI subnetwork containing 16 nodes was also identified, including: Transcription factor GATA?4; fibroblast growth factor 9; aromatase; 3??hydroxysteroid dehydrogenase/?5?4?isomerase type 2; corticosteroid 11??dehydrogenase isozyme 1; CYP17A1; pituitary homeobox 2; left?right determination factor 1; homeobox protein ARX; estrogen receptor ?; steroidogenic factor 1; forkhead box protein L2; myocardin; steroidogenic acute regulatory protein mitochondrial; vesicular inhibitory amino acid transporter; and twist?related protein 1. A random forest classifier was constructed using the subnetwork nodes as feature genes, which exhibited a 92% true positive rate when classifying recurrent and non?recurrent OC samples. The classifying efficiency of the random forest classifier was validated using the two other independent datasets. Overall, 44 upregulated and 117 downregulated genes associated with OC recurrence were identified. Furthermore, the 16 subnetwork node genes that were identified may be important molecules in OC recurrence.

Project description:Mouse embryonic stem cells (mESCs) are derived from the inner cell mass of a developing blastocyst and can be cultured indefinitely in-vitro. Their distinct features are their ability to self-renew and to differentiate to all adult cell types. Genes that maintain mESCs self-renewal and pluripotency identity are of interest to stem cell biologists. Although significant steps have been made toward the identification and characterization of such genes, the list is still incomplete and controversial. For example, the overlap among candidate self-renewal and pluripotency genes across different RNAi screens is surprisingly small. Meanwhile, machine learning approaches have been used to analyze multi-dimensional experimental data and integrate results from many studies, yet they have not been applied to specifically tackle the task of predicting and classifying self-renewal and pluripotency gene membership.For this study we developed a classifier, a supervised machine learning framework for predicting self-renewal and pluripotency mESCs stemness membership genes (MSMG) using support vector machines (SVM). The data used to train the classifier was derived from mESCs-related studies using mRNA microarrays, measuring gene expression in various stages of early differentiation, as well as ChIP-seq studies applied to mESCs profiling genome-wide binding of key transcription factors, such as Nanog, Oct4, and Sox2, to the regulatory regions of other genes. Comparison to other classification methods using the leave-one-out cross-validation method was employed to evaluate the accuracy and generality of the classification. Finally, two sets of candidate genes from genome-wide RNA interference screens are used to test the generality and potential application of the classifier.Our results reveal that an SVM approach can be useful for prioritizing genes for functional validation experiments and complement the analyses of high-throughput profiling experimental data in stem cell research.

Project description:BackgroundLong non-coding RNAs (lncRNAs), which have little or no ability to encode proteins, have attracted special attention due to their potential role in cancer disease. In this study we aimed to establish a lncRNAs classifier to improve the accuracy of recurrence prediction for thymic epithelial tumors (TETs).MethodsTETs RNA sequencing (RNA-seq) data set and the matched clinicopathologic information were downloaded from the Cancer Genome Atlas. Using univariate Cox regression and least absolute shrinkage and selection operator (LASSO) analysis, we developed a lncRNAs classifier related to recurrence. Functional analysis was conducted to investigate the potential biological processes of the lncRNAs target genes. The independent prognostic factors were identified by Cox regression model. Additionally, predictive ability and clinical application of the lncRNAs classifier were assessed, and compared with the Masaoka staging by receiver operating characteristic (ROC) analysis and decision curve analysis (DCA).ResultsFour recurrence-free survival (RFS)-related lncRNAs were identified, and the classifier consisting of the identified four lncRNAs was able to effectively divide the patients into high and low risk subgroups, with an area under curve (AUC) of 0.796 (three-year RFS) and 0.788 (five-year RFS), respectively. Multivariate analysis indicated that the lncRNAs classifier was an independent recurrence risk factor. The AUC of the lncRNAs classifier in predicting RFS was significantly higher than the Masaoka staging system. Decision curve analysis further demonstrated that the lncRNAs classifier had a larger net benefit than the Masaoka staging system.ConclusionsA lncRNAs classifier for patients with TETs was an independent risk factor for RFS despite other clinicopathologic variables. It generated more accurate estimations of the recurrence probability when compared to the Masaoka staging system, but additional data is required before it can be used in clinical practice.

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Dataset Information

Establishment of a SVM classifier to predict recurrence of ovarian cancer.

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Establishment of a SVM classifier to predict recurrence of ovarian cancer.

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