Publications by authors named "Doron Stupp"
Conservation is a strong predictor for the pathogenicity of single-nucleotide variants (SNVs). However, some positions that present complex conservation patterns across vertebrates stray from this paradigm. Here, we analyzed the association between complex conservation patterns and the pathogenicity of SNVs in the 115 disease-genes that had sufficient variant data.
View Article and Find Full Text PDFOver the next decade, more than a million eukaryotic species are expected to be fully sequenced. This has the potential to improve our understanding of genotype and phenotype crosstalk, gene function and interactions, and answer evolutionary questions. Here, we develop a machine-learning approach for utilizing phylogenetic profiles across 1154 eukaryotic species.
View Article and Find Full Text PDFMapping co-evolved genes via phylogenetic profiling (PP) is a powerful approach to uncover functional interactions between genes and to associate them with pathways. Despite many successful endeavors, the understanding of co-evolutionary signals in eukaryotes remains partial. Our hypothesis is that 'Clades', branches of the tree of life (e.
View Article and Find Full Text PDFSummary: The exponential growth in available genomic data is expected to reach full sequencing of a million genomes in the coming decade. Improving and developing methods to analyze these genomes and to reveal their utility is of major interest in a wide variety of fields, such as comparative and functional genomics, evolution and bioinformatics. Phylogenetic profiling is an established method for predicting functional interactions between proteins based on similarities in their evolutionary patterns across species.
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- Cell state-specific promoters are crucial for research as they enable gene expression under specific biological conditions.
- The study employs next-generation sequencing and machine learning to analyze over 6,100 synthetic promoter designs to create high-performance synthetic promoters with enhanced specificity for various cell states.
- The researchers successfully identified several synthetic promoters that show unique activity patterns during the differentiation of induced pluripotent stem cells and for specific cancer stem cells, suggesting potential applications in gene therapy and transcriptional studies.
Myotonic dystrophy type 1 is an autosomal-dominant inherited disorder caused by the expansion of CTG repeats in the 3' untranslated region of the DMPK gene. The RNAs bearing these expanded repeats have a range of toxic effects. Here we provide evidence from a Caenorhabditis elegans myotonic dystrophy type 1 model that the RNA interference (RNAi) machinery plays a key role in causing RNA toxicity and disease phenotypes.
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- Cancer immunotherapy has shown promise in clinical trials but faces challenges like the scarcity of targetable antigens and immune suppression by tumors.
- The study introduces a new gene circuit platform that targets tumors specifically by using synthetic promoters and an RNA-based AND gate to deliver customized immunostimulatory signals only in the presence of cancer cells.
- Results demonstrated that this approach selectively killed cancer cells while sparing normal cells in the lab, and in mouse models, it significantly reduced tumors and improved survival, indicating potential for broader applications in immunotherapy.