Research projects

The role of RNA conformations in RNA-protein recognition
In this project we studied protein-RNA structures from 9 RNA binding protein families extracted from the PDB and characterized the structural properties of RNA within the interfaces. In addition, we looked on RNA-protein interactions and examined the sequences binding the RRM domain.
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Conformational readout of RNA by small ligands
In this project we studied RNA ligand complexes from 10 RNA groups extracted from the PDB and analyzed the chemical, physical, structural and conformational properties of binding pockets around the ligand.
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PatchBag - a novel approach for quick detection of interface similarity and complementarity
With the growing amount of protein structures, new methods for identifying functional similarities are critically needed. We developed PatchBag, a vector representation of the protein surface that enables rapid and accurate identification of surface similarity and interface complementarity on large datasets, based on a ‘bag-of-words’ approach.
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Identifying functional sites in proteins using a multilevel alphabet
A new approach that translates a protein amino acid sequence into a new alphabet, looking simultaneously at different levels of the protein residues, which reflect its intrinsic structural and chemical properties.
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Widespread evidence to the role of flanking regions on transcription factor binding preferences
Recent studies suggest that on average 99.8% of transcription factor binding motifs in the human genome are unbound by the respective transcription factor. In our study we investigate what distinguishes a “binding motif” from another similar motif which does not bind protein within the same genomic environment. We show that DNA features far beyond the core motif contribute to DNA recognition by transcription factors. Interestingly, these features are characteristic of the transcription factor family.
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Covariation between homeodomain transcription factors and the shape of their DNA binding sites
We study the principles of DNA recognition by transcription factors. In this work we concentrated on the homeodomain family, the second most abundant family of transcription factors in humans. We identified specific homeodomain residues that likely play key roles in DNA recognition via “shape readout” and showed that adding DNA shape information improved the prediction accuracy of homeodomain binding specificities.
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An epigenetic signature at intragenic exons with implication for expression
While the role of CpG methylation at the gene promoter is well characterized, the function of DNA methylation and histone modifications within the gene, specifically at intragenic exons, remains unclear. In this study we investigated the relationship between DNA methylation and histone modifications at intragenic exons and the exon expression in Human tissue culture and primary cells. Consistent with previous work we found that DNA methylation within the gene is positively correlated with its expression. Moreover we identified a set of hypo-methylated exons widespread in the genome that have a unique epigenetic signature positively correlated with expression.
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An integrated regulatory network reveals pervasive cross-regulation among transcription and splicing factors
To date there is increasing evidence of coupling between transcription and splicing regulation. In this study, we modeled a network integrating the two regulations. Analysis of the network indicated that splicing factors were more often regulated by alternative splicing while transcription factors were more extensively controlled by transcriptional regulation. Overall, we postulate that regulatory proteins in the cell are controlled preferentially by the specific regulation they conduct.
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Comparative metagenomic analyses reveal viral-induced shifts of host metabolism towards nucleotide biosynthesis
Viral genomes often contain metabolic genes that were acquired from host genomes (auxiliary genes). It is assumed that these genes are fixed in viral genomes as a result of a selective force, favoring viruses that acquire specific metabolic functions. In this study, we identify a set of statistically enriched auxiliary genes in marine viral metagenomes. These genes are assigned to a global metabolism network we created. Our analysis suggests that many of the metabolic functions enriched in the viral metagenomes induce shift in the host metabolism, upon infection, towards nucleotide recycling and deoxynucleotide synthesis.
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Cyanophage tRNAs may have a role in cross-infectivity of oceanic Prochlorococcus and Synechococcus hosts
We study marine phages of the myoviridae family, which infect cyanobacteria and therefore have a huge ecological importance. In this project we found evidence for the contribution of viral tRNA genes to viral gene translation, when infecting hosts with differnet G+C content. Our hypotheses are now being tested, using an "evolution in a test tube" experiment.
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