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Biology subjects

Onah, D.

Publications and source records attributed to Onah, D..

2 recordsLinked to original sources

Predicting Gene Disease Associations in Type 2 Diabetes Using Machine Learning on Single-Cell RNA-Seq Data

Diabetes is a chronic metabolic disorder characterized by elevated blood glucose levels due to impaired insulin production or function. Two main forms are recognized: type 1 diabetes (T1D), which involves autoimmune destruction of insulin-producing {beta}-cells, and type 2 diabetes (T2D), which arises from insulin resistance and progressive {beta}-cell dysfunction. Understanding the molecular mechanisms underlying these diseases is essential for the development of improved therapeutic strategies, particularly those targeting {beta}-cell dysfunction. To investigate these mechanisms in a controlled and biologically interpretable setting, mouse models have played a central role in diabetes research. Owing to their genetic and physiological similarity to humans, together with the ability to precisely manipulate their genome, mice enable detailed investigation of disease progression and gene function. In particular, mouse models have provided critical insights into {beta}-cell development, cellular heterogeneity, and functional failure under diabetic conditions. Building on these experimental advances, this study applies machine learning methods to single-cell transcriptomic data from mouse pancreatic islets. Specifically, we evaluate two supervised approaches identified in the literature; Extra Trees Classifier (ETC) and Partial Least Squares Discriminant Analysis (PLS-DA), to assess their ability to identify T2D-associated gene expression signatures at single-cell resolution. Model performance is evaluated using standard classification metrics, with an emphasis on interpretability and biological relevance.

bioinformatics↗

G2P: Using machine learning to understand and predict genes causing rare neurological disorders

To facilitate precision medicine and neuroscience research, we developed a machine-learning technique that scores the likelihood that a gene, when mutated, will cause a neurological phenotype. We analysed 1126 genes relating to 25 subtypes of Mendelian neurological disease defined by Genomics England (March 2017) together with 154 gene-specific features capturing genetic variation, gene structure and tissue-specific expression and co-expression. We randomly re-sampled genes with no known disease association to develop bootstrapped decision-tree models, which were integrated to generate a decision tree-based ensemble for each disease subtype. Genes generating larger numbers of distinct transcripts and with higher probability of having missense mutations in normal individuals were significantly more likely to cause neurological diseases. Using mouse-mutant phenotypic data we tested the accuracy of gene-phenotype predictions and found that for 88% of all disease subtypes there was a significant enrichment of relevant phenotypic abnormalities when predicted genes were mutated in mice and in many cases mutations produced specific and matching phenotypes. Furthermore, using only newly identified genes included in the Genomics England November 2017 release, we assessed our gene-phenotype predictions and showed an 8.3 fold enrichment relative to chance for correct predictions. Thus, we demonstrate both the explanatory and predictive power of machine-learning-based models in neurological disease.

genetics↗