Dataset Information

A Machine Learning Approach to Predicting Autism Risk Genes: Validation of Known Genes and Discovery of New Candidates.

ABSTRACT: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with a strong genetic basis. The role of de novo mutations in ASD has been well established, but the set of genes implicated to date is still far from complete. The current study employs a machine learning-based approach to predict ASD risk genes using features from spatiotemporal gene expression patterns in human brain, gene-level constraint metrics, and other gene variation features. The genes identified through our prediction model were enriched for independent sets of ASD risk genes, and tended to be down-expressed in ASD brains, especially in frontal and parietal cortex. The highest-ranked genes not only included those with strong prior evidence for involvement in ASD (for example, NBEA, HERC1, and TCF20), but also indicated potentially novel candidates, such as, MYCBP2 and CAND1, which are involved in protein ubiquitination. We also showed that our method outperformed state-of-the-art scoring systems for ranking curated ASD candidate genes. Gene ontology enrichment analysis of our predicted risk genes revealed biological processes clearly relevant to ASD, including neuronal signaling, neurogenesis, and chromatin remodeling, but also highlighted other potential mechanisms that might underlie ASD, such as regulation of RNA alternative splicing and ubiquitination pathway related to protein degradation. Our study demonstrates that human brain spatiotemporal gene expression patterns and gene-level constraint metrics can help predict ASD risk genes. Our gene ranking system provides a useful resource for prioritizing ASD candidate genes.

SUBMITTER: Lin Y

PROVIDER: S-EPMC7513695 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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A Machine Learning Approach to Predicting Autism Risk Genes: Validation of Known Genes and Discovery of New Candidates.

Lin Ying Y Afshar Shiva S Rajadhyaksha Anjali M AM Potash James B JB Han Shizhong S

Frontiers in genetics 20200910

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with a strong genetic basis. The role of <i>de novo</i> mutations in ASD has been well established, but the set of genes implicated to date is still far from complete. The current study employs a machine learning-based approach to predict ASD risk genes using features from spatiotemporal gene expression patterns in human brain, gene-level constraint metrics, and other gene variation features. The genes identified through ou ...[more]

PMID: 33133139

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Project description:BackgroundThe Centers for Medicare and Medicaid Services projects that health care costs will continue to grow over the next few years. Rising readmission costs contribute significantly to increasing health care costs. Multiple areas of health care, including readmissions, have benefited from the application of various machine learning algorithms in several ways.ObjectiveWe aimed to identify suitable models for predicting readmission charges billed by hospitals. Our literature review revealed that this application of machine learning is underexplored. We used various predictive methods, ranging from glass-box models (such as regularization techniques) to black-box models (such as deep learning-based models).MethodsWe defined readmissions as readmission with the same major diagnostic category (RSDC) and all-cause readmission category (RADC). For these readmission categories, 576,701 and 1,091,580 individuals, respectively, were identified from the Nationwide Readmission Database of the Healthcare Cost and Utilization Project by the Agency for Healthcare Research and Quality for 2013. Linear regression, lasso regression, elastic net, ridge regression, eXtreme gradient boosting (XGBoost), and a deep learning model based on multilayer perceptron (MLP) were the 6 machine learning algorithms we tested for RSDC and RADC through 10-fold cross-validation.ResultsOur preliminary analysis using a data-driven approach revealed that within RADC, the subsequent readmission charge billed per patient was higher than the previous charge for 541,090 individuals, and this number was 319,233 for RSDC. The top 3 major diagnostic categories (MDCs) for such instances were the same for RADC and RSDC. The average readmission charge billed was higher than the previous charge for 21 of the MDCs in the case of RSDC, whereas it was only for 13 of the MDCs in RADC. We recommend XGBoost and the deep learning model based on MLP for predicting readmission charges. The following performance metrics were obtained for XGBoost: (1) RADC (mean absolute percentage error [MAPE]=3.121%; root mean squared error [RMSE]=0.414; mean absolute error [MAE]=0.317; root relative squared error [RRSE]=0.410; relative absolute error [RAE]=0.399; normalized RMSE [NRMSE]=0.040; mean absolute deviation [MAD]=0.031) and (2) RSDC (MAPE=3.171%; RMSE=0.421; MAE=0.321; RRSE=0.407; RAE=0.393; NRMSE=0.041; MAD=0.031). The performance obtained for MLP-based deep neural networks are as follows: (1) RADC (MAPE=3.103%; RMSE=0.413; MAE=0.316; RRSE=0.410; RAE=0.397; NRMSE=0.040; MAD=0.031) and (2) RSDC (MAPE=3.202%; RMSE=0.427; MAE=0.326; RRSE=0.413; RAE=0.399; NRMSE=0.041; MAD=0.032). Repeated measures ANOVA revealed that the mean RMSE differed significantly across models with P<.001. Post hoc tests using the Bonferroni correction method indicated that the mean RMSE of the deep learning/XGBoost models was statistically significantly (P<.001) lower than that of all other models, namely linear regression/elastic net/lasso/ridge regression.ConclusionsModels built using XGBoost and MLP are suitable for predicting readmission charges billed by hospitals. The MDCs allow models to accurately predict hospital readmission charges.

Dataset Information

A Machine Learning Approach to Predicting Autism Risk Genes: Validation of Known Genes and Discovery of New Candidates.

Publications

A Machine Learning Approach to Predicting Autism Risk Genes: Validation of Known Genes and Discovery of New Candidates.

Similar Datasets

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