A5004761084- Bioinformatics and Genomic Networks
- Genomics and Phylogenetic Studies
- Genetics and Neurodevelopmental Disorders
- Genomics and Rare Diseases
- Genomic variations and chromosomal abnormalities
- Endoplasmic Reticulum Stress and Disease
- Photosynthetic Processes and Mechanisms
- Cancer Genomics and Diagnostics
- Monoclonal and Polyclonal Antibodies Research
- Evolution and Paleontology Studies
- RNA modifications and cancer
- CRISPR and Genetic Engineering
- DNA Repair Mechanisms
- Algal biology and biofuel production
- Machine Learning in Bioinformatics
- HER2/EGFR in Cancer Research
- Protein Structure and Dynamics
- Microbial Metabolic Engineering and Bioproduction
- Gene expression and cancer classification
- Evolution and Genetic Dynamics
- Primate Behavior and Ecology
- Genetic factors in colorectal cancer
- Computational Drug Discovery Methods
- Marine animal studies overview
- Ubiquitin and proteasome pathways
Hebrew University of Jerusalem
2019-2024
Hadassah Medical Center
2019-2020
The homologous recombination repair (HRR) pathway repairs DNA double-strand breaks in an error-free manner. Mutations HRR genes can result increased mutation rate and genomic rearrangements, are associated with numerous genetic disorders cancer. Despite intensive research, the is not yet fully mapped. Phylogenetic profiling analysis, which detects functional linkage between using coevolution, a powerful approach to identify factors many pathways. Nevertheless, phylogenetic has limited...
Mapping co-evolved genes via phylogenetic profiling (PP) is a powerful approach to uncover functional interactions between and associate them with pathways. Despite many successful endeavors, the understanding of co-evolutionary signals in eukaryotes remains partial. Our hypothesis that 'Clades', branches tree life (e.g. primates mammals), encompass cannot be detected by PP using all eukaryotes. As such, integrating information from different clades should reveal local co-evolution improve...
Abstract Over the next decade, more than a million eukaryotic species are expected to be fully sequenced. This has potential improve our understanding of genotype and phenotype crosstalk, gene function interactions, answer evolutionary questions. Here, we develop machine-learning approach for utilizing phylogenetic profiles across 1154 species. method integrates co-evolution clades predict functional interactions between human genes context these interactions. We benchmark showing 14%...
Inactivating mutations in the Methyl-CpG Binding Protein 2 (MECP2) gene are main cause of Rett syndrome (RTT). Despite extensive research into MECP2 function, no treatments for RTT currently available. Here, we used an evolutionary genomics approach to construct unbiased network, using 1028 eukaryotic genomes prioritize proteins with strong co-evolutionary signatures MECP2. Focusing on targeted by FDA-approved drugs led three promising targets, two which were previously linked function...
Abstract Background Next-generation sequencing (NGS) has significantly transformed the landscape of identifying disease-causing genes associated with genetic disorders. However, a substantial portion sequenced patients remains undiagnosed. This may be attributed not only to challenges posed by harder-to-detect variants, such as non-coding and structural variations but also existence variants in previously patient’s clinical phenotype. study introduces EvORanker, an algorithm that integrates...
The exponential growth in available genomic data is expected to reach full sequencing of a million genomes the coming decade. Improving and developing methods analyze these reveal their utility major interest wide variety fields, such as comparative functional genomics, evolution bioinformatics. Phylogenetic profiling an established method for predicting interactions between proteins based on similarities evolutionary patterns across species. Proteins that function together (i.e. generate...
DNA repair by homologous recombination (HR) is critical for the maintenance of genome stability. Germline and somatic mutations in HR genes have been associated with an increased risk developing breast (BC) ovarian cancers (OvC). However, extent factors pathways that are functionally linked to clinical relevance BC OvC remains unclear. To gain a broader understanding this pathway, we used multi-omics datasets coupled machine learning identify predict their sub-function. Specifically,...
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 association between and SNVs in 115 disease-genes had sufficient variant data. We show not one-rule-fits-all solution since its accuracy highly depends on set species genes. For example, pairwise comparisons human 99 vertebrate showed differ their ability to predict...
Abstract ERBB2 amplification is a prognostic marker for aggressive tumors and predictive prolonged survival following treatment with HER2 inhibitors. We attempt to sub-group HER2+ based on amplicon structures co-amplified genes. examined five cell lines, three xenographs 57 tumor tissues. was analyzed using digital droplet PCR low coverage whole genome sequencing. In some PPM1D , that encodes WIP1, co-amplified. Cell lines were treated WIP1 find inverted duplication the structure in majority...
Cross-species protein conservation patterns, as directed by natural selection, are indicative of the interplay between function, protein-protein interaction and evolution. Since beginning genomic era, proteins were characterized either conserved or not conserved. This simple classification became archaic cursory once data on orthologs available for thousands species. To enrich language used to describe understand their biological significance, we classified 20,294 human against 1096 Analyses...
Abstract Inactivating mutations in the Methyl-CpG Binding Protein 2 (MECP2) gene are main cause of Rett syndrome (RTT). Despite extensive research into MECP2 function, no treatments for RTT currently available. Here we use an evolutionary genomics approach to construct unbiased network, using 1,028 eukaryotic genomes prioritize proteins with strong co-evolutionary signatures MECP2. Focusing on targeted by FDA approved drugs led three promising candidates, two which were previously linked...