Dataset Information

Machine Learning-Based Approach Highlights the Use of a Genomic Variant Profile for Precision Medicine in Ovarian Failure.

ABSTRACT: Ovarian failure (OF) is a common cause of infertility usually diagnosed as idiopathic, with genetic causes accounting for 10-25% of cases. Whole-exome sequencing (WES) may enable identifying contributing genes and variant profiles to stratify the population into subtypes of OF. This study sought to identify a blood-based gene variant profile using accumulation of rare variants to promote precision medicine in fertility preservation programs. A case-control (n = 118, n = 32, respectively) WES study was performed in which only non-synonymous rare variants <5% minor allele frequency (MAF; in the IGSR) and coverage ≥ 100× were considered. A profile of 66 variants of uncertain significance was used for training an unsupervised machine learning model to separate cases from controls (97.2% sensitivity, 99.2% specificity) and stratify the population into two subtypes of OF (A and B) (93.31% sensitivity, 96.67% specificity). Model testing within the IGSR female population predicted 0.5% of women as subtype A and 2.4% as subtype B. This is the first study linking OF to the accumulation of rare variants and generates a new potential taxonomy supporting application of this approach for precision medicine in fertility preservation.

SUBMITTER: Henarejos-Castillo I

PROVIDER: S-EPMC8305607 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Chronic kidney disease (CKD) is a significant global health challenge that requires timely detection and accurate prognosis for effective treatment and management. The application of machine learning (ML) algorithms for CKD detection and prediction holds promising potential for improving patient outcomes. By incorporating key features which contribute to CKD, these algorithms enhance our ability to identify high-risk individuals and initiate timely interventions. This research highlights the importance of leveraging machine learning techniques to augment existing medical knowledge and improve the identification and management of kidney disease. In this paper, we explore the utilization of diverse ML algorithms, including gradient boost (GB), decision tree (DT), K-nearest neighbor (KNN), random forest (RF), histogram boost (HB), and XGBoost (XGB) to detect and predict chronic kidney disease (CKD). The aim is to improve early detection and prognosis, enhancing patient outcomes and reducing the burden on healthcare systems. We evaluated the performance of the ML algorithms using key metrics like accuracy, precision, recall, and F1 score. Additionally, we conducted feature significance analysis to identify the most influential characteristics in the detection and prediction of kidney disease. The dataset used for training and evaluation contained various clinical and demographic attributes of patients, including serum creatinine level, blood pressure, and age, among others. The proficiency analysis of the ML algorithms revealed consistent predictors across all models, with serum creatinine level, blood pressure, and age emerging as particularly effective in identifying individuals at risk of kidney disease. These findings align with established medical knowledge and emphasize the pivotal role of these attributes in early detection and prognosis. In conclusion, our study demonstrates the effectiveness of diverse machine learning algorithms in detecting and predicting kidney disease. The identification of influential predictors, such as serum creatinine level, blood pressure, and age, underscores their significance in early detection and prognosis. By leveraging machine learning techniques, we can enhance the accuracy and efficiency of kidney disease diagnosis and treatment, ultimately improving patient outcomes and healthcare system effectiveness.

Project description:Ovarian cancer (OC) is a type of malignant tumor with a consistently high mortality rate. The diagnosis of early-stage OC and identification of functional subsets in the tumor microenvironment are essential to the development of patient management strategies. However, the development of robust models remains unsatisfactory. We aimed to utilize artificial intelligence and single-cell analysis to address this issue. Two independent datasets were screened from the Gene Expression Omnibus (GEO) database and processed to obtain overlapping differentially expressed genes (DEGs) in stage II-IV vs. stage I diseases. Three explainable machine learning algorithms were integrated to construct models that could determine the tumor stage and extract important characteristic genes as diagnostic biomarkers. Correlations between cancer-associated fibroblast (CAF) infiltration and characteristic gene expression were analyzed using TIMER2.0 and their relationship with survival rates was comprehensively explored via the Kaplan-Meier plotter (KM-plotter) online database. The specific expression of characteristic genes in fibroblast subsets was investigated through single-cell analysis. A novel fibroblast subset signature was explored to predict immune checkpoint inhibitor (ICI) response and oncogene mutation through Tumor Immune Dysfunction and Exclusion (TIDE) and artificial neural network algorithms, respectively. We found that Support Vector Machine-Shapley Additive Explanations (SVM-SHAP), Extreme Gradient Boosting (XGBoost), and Random Forest (RF) successfully diagnosed early-stage OC (stage I). The area under the receiver operating characteristic curves (AUCs) of these models exceeded 0.990. Their overlapping characteristic gene, secreted frizzled-related protein 2 (SFRP2), was a risk factor that affected the overall survival of OC patients with stage II-IV disease (log-rank test: p < 0.01) and was specifically expressed in a fibroblast subset. Finally, the SFRP2+ fibroblast signature served as a novel predictor in evaluating ICI response and exploring pan-cancer tumor protein P53 (TP53) mutation (AUC = 0.853, 95% confidence interval [CI]: 0.829-0.877). In conclusion, the models based on SVM-SHAP, XGBoost, and RF enabled the early detection of OC for clinical decision making, and SFRP2+ fibroblast signature used in diagnostic models can inform OC treatment selection and offer pan-cancer TP53 mutation detection.

Dataset Information

Machine Learning-Based Approach Highlights the Use of a Genomic Variant Profile for Precision Medicine in Ovarian Failure.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets