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Developing an Explainable Machine Learning-Based Personalised Dementia Risk Prediction Model: A Transfer Learning Approach With Ensemble Learning Algorithms.

ABSTRACT: Alzheimer's disease (AD) has its onset many decades before dementia develops, and work is ongoing to characterise individuals at risk of decline on the basis of early detection through biomarker and cognitive testing as well as the presence/absence of identified risk factors. Risk prediction models for AD based on various computational approaches, including machine learning, are being developed with promising results. However, these approaches have been criticised as they are unable to generalise due to over-reliance on one data source, poor internal and external validations, and lack of understanding of prediction models, thereby limiting the clinical utility of these prediction models. We propose a framework that employs a transfer-learning paradigm with ensemble learning algorithms to develop explainable personalised risk prediction models for dementia. Our prediction models, known as source models, are initially trained and tested using a publicly available dataset (n = 84,856, mean age = 69 years) with 14 years of follow-up samples to predict the individual risk of developing dementia. The decision boundaries of the best source model are further updated by using an alternative dataset from a different and much younger population (n = 473, mean age = 52 years) to obtain an additional prediction model known as the target model. We further apply the SHapely Additive exPlanation (SHAP) algorithm to visualise the risk factors responsible for the prediction at both population and individual levels. The best source model achieves a geometric accuracy of 87%, specificity of 99%, and sensitivity of 76%. In comparison to a baseline model, our target model achieves better performance across several performance metrics, within an increase in geometric accuracy of 16.9%, specificity of 2.7%, and sensitivity of 19.1%, an area under the receiver operating curve (AUROC) of 11% and a transfer learning efficacy rate of 20.6%. The strength of our approach is the large sample size used in training the source model, transferring and applying the "knowledge" to another dataset from a different and undiagnosed population for the early detection and prediction of dementia risk, and the ability to visualise the interaction of the risk factors that drive the prediction. This approach has direct clinical utility.

SUBMITTER: Danso SO

PROVIDER: S-EPMC8187875 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:In plants, long non-protein coding RNAs are believed to have essential roles in development and stress responses. However, relative to advances on discerning biological roles for long non-protein coding RNAs in animal systems, this RNA class in plants is largely understudied. With comparatively few validated plant long non-coding RNAs, research on this potentially critical class of RNA is hindered by a lack of appropriate prediction tools and databases. Supervised learning models trained on data sets of mostly non-validated, non-coding transcripts have been previously used to identify this enigmatic RNA class with applications largely focused on animal systems. Our approach uses a training set comprised only of empirically validated long non-protein coding RNAs from plant, animal, and viral sources to predict and rank candidate long non-protein coding gene products for future functional validation. RESULTS:Individual stochastic gradient boosting and random forest classifiers trained on only empirically validated long non-protein coding RNAs were constructed. In order to use the strengths of multiple classifiers, we combined multiple models into a single stacking meta-learner. This ensemble approach benefits from the diversity of several learners to effectively identify putative plant long non-coding RNAs from transcript sequence features. When the predicted genes identified by the ensemble classifier were compared to those listed in GreeNC, an established plant long non-coding RNA database, overlap for predicted genes from Arabidopsis thaliana, Oryza sativa and Eutrema salsugineum ranged from 51 to 83% with the highest agreement in Eutrema salsugineum. Most of the highest ranking predictions from Arabidopsis thaliana were annotated as potential natural antisense genes, pseudogenes, transposable elements, or simply computationally predicted hypothetical protein. Due to the nature of this tool, the model can be updated as new long non-protein coding transcripts are identified and functionally verified. CONCLUSIONS:This ensemble classifier is an accurate tool that can be used to rank long non-protein coding RNA predictions for use in conjunction with gene expression studies. Selection of plant transcripts with a high potential for regulatory roles as long non-protein coding RNAs will advance research in the elucidation of long non-protein coding RNA function.

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Developing an Explainable Machine Learning-Based Personalised Dementia Risk Prediction Model: A Transfer Learning Approach With Ensemble Learning Algorithms.

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