Publications by authors named "N Ioannidis"
Article Synopsis
- - Kidney failure significantly impacts health, prompting a large-scale study of 406,504 participants to uncover genetic factors affecting kidney function, identifying 430 key genetic loci.
- - The research revealed that 56% of inherited differences in kidney function are linked to regulatory elements in kidney tubule epithelial cells, while 7% relate to podocyte cells, suggesting these are crucial for gene expression.
- - Further analysis using advanced techniques like enhancer assays and CRISPRi identified specific genes (NDRG1, CCNB1, and STC1) regulated by these genetic loci, shedding light on their roles in kidney function.
Article Synopsis
- Deep learning models are used to predict epigenetic features, but their performance varies, especially in cell type-specific regions crucial for gene regulation.
- The study compares general-purpose models and tissue-specific models, finding that tailored models can enhance accuracy in predicting chromatin accessibility in specific cells.
- It emphasizes the need for novel strategies to improve predictions on genetic variants, as high reference sequence accuracy does not guarantee better variant effect predictions.
Article Synopsis
- A variety of deep learning models are being developed to predict chromatin accessibility from DNA sequences, but evaluation results often overlook the significance of cell type specific regulatory elements (CREs), which are crucial for gene regulation and complex disease heritability.
- The study evaluates the accuracy of these genomic models, revealing that general purpose models like Enformer and Sei perform worse in regions that are specifically accessible to certain cell types.
- The research highlights that tailoring models for specific tissues and enhancing their capacity for cell type specific regulation can boost performance, but improving predictions of reference sequences doesn't necessarily translate to better predictions of variant effects, suggesting the need for new approaches in the field.
Article Synopsis
- Kidney disease is largely influenced by genetics, yet the specific genes and mechanisms involved are still not fully understood; a recent GWAS identified 462 genetic loci associated with kidney function.
- Researchers used single-cell ATAC-seq maps to explore chromatin accessibility in the kidney, finding that regulatory elements in kidney tubule epithelial cells accounted for the majority of genetic heritability related to kidney function.
- The study further utilized CRISPR interference to demonstrate how inherited variations in regulatory elements impact gene expression in tubule epithelial cells, ultimately linking these differences to a predisposition for kidney disease in humans.
Gene therapies have the potential to treat disease by delivering therapeutic genetic cargo to disease-associated cells. One limitation to their widespread use is the lack of short regulatory sequences, or promoters, that differentially induce the expression of delivered genetic cargo in target cells, minimizing side effects in other cell types. Such cell-type-specific promoters are difficult to discover using existing methods, requiring either manual curation or access to large datasets of promoter-driven expression from both targeted and untargeted cells.
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