Dataset Information

An Ovarian Cancer Susceptible Gene Prediction Method Based on Deep Learning Methods.

ABSTRACT: Ovarian cancer (OC) is one of the most fatal diseases among women all around the world. It is highly lethal because it is usually diagnosed at an advanced stage which may reduce the survival rate greatly. Even though most of the patients are treated timely and effectively, the survival rate is still low due to the high recurrence rate of OC. With a large number of genome-wide association analysis (GWAS)-discovered risk regions of OC, expression quantitative trait locus (eQTL) analyses can explore candidate susceptible genes based on these risk loci. However, a large number of OC-related genes remain unknown. In this study, we proposed a novel gene prediction method based on different omics data and deep learning methods to identify OC causal genes. We first employed graph attention network (GAT) to obtain a compact gene feature representation, then a deep neural network (DNN) is utilized to predict OC-related genes. As a result, our model achieved a high AUC of 0.761 and AUPR of 0.788, which proved the accuracy and effectiveness of our proposed method. At last, we conducted a gene-set enrichment analysis to further explore the mechanism of OC. Finally, we predicted 245 novel OC causal genes and 10 top related KEGG pathways.

SUBMITTER: Ye L

PROVIDER: S-EPMC8414800 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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An Ovarian Cancer Susceptible Gene Prediction Method Based on Deep Learning Methods.

Ye Lu L Zhang Yi Y Yang Xinying X Shen Fei F Xu Bo B

Frontiers in cell and developmental biology 20210813

Ovarian cancer (OC) is one of the most fatal diseases among women all around the world. It is highly lethal because it is usually diagnosed at an advanced stage which may reduce the survival rate greatly. Even though most of the patients are treated timely and effectively, the survival rate is still low due to the high recurrence rate of OC. With a large number of genome-wide association analysis (GWAS)-discovered risk regions of OC, expression quantitative trait locus (eQTL) analyses can explor ...[more]

PMID: 34485310

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Project description:BackgroundOvarian cancer remains the leading gynecological cause of cancer mortality. Predicting the sensitivity of ovarian cancer to chemotherapy at the time of pathological diagnosis is a goal of precision medicine research that we have addressed in this study using a novel deep-learning neural network framework to analyze the histopathological images.MethodsWe have developed a method based on the Inception V3 deep learning algorithm that complements other methods for predicting response to standard platinum-based therapy of the disease. For the study, we used histopathological H&E images (pre-treatment) of high-grade serous carcinoma from The Cancer Genome Atlas (TCGA) Genomic Data Commons portal to train the Inception V3 convolutional neural network system to predict whether cancers had independently been labeled as sensitive or resistant to subsequent platinum-based chemotherapy. The trained model was then tested using data from patients left out of the training process. We used receiver operating characteristic (ROC) and confusion matrix analyses to evaluate model performance and Kaplan-Meier survival analysis to correlate the predicted probability of resistance with patient outcome. Finally, occlusion sensitivity analysis was piloted as a start toward correlating histopathological features with a response.ResultsThe study dataset consisted of 248 patients with stage 2 to 4 serous ovarian cancer. For a held-out test set of forty patients, the trained deep learning network model distinguished sensitive from resistant cancers with an area under the curve (AUC) of 0.846 ± 0.009 (SE). The probability of resistance calculated from the deep-learning network was also significantly correlated with patient survival and progression-free survival. In confusion matrix analysis, the network classifier achieved an overall predictive accuracy of 85% with a sensitivity of 73% and specificity of 90% for this cohort based on the Youden-J cut-off. Stage, grade, and patient age were not statistically significant for this cohort size. Occlusion sensitivity analysis suggested histopathological features learned by the network that may be associated with sensitivity or resistance to the chemotherapy, but multiple marker studies will be necessary to follow up on those preliminary results.ConclusionsThis type of analysis has the potential, if further developed, to improve the prediction of response to therapy of high-grade serous ovarian cancer and perhaps be useful as a factor in deciding between platinum-based and other therapies. More broadly, it may increase our understanding of the histopathological variables that predict response and may be adaptable to other cancer types and imaging modalities.

Dataset Information

An Ovarian Cancer Susceptible Gene Prediction Method Based on Deep Learning Methods.

Publications

An Ovarian Cancer Susceptible Gene Prediction Method Based on Deep Learning Methods.

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