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Noam Shomron

Bio: Noam Shomron is an academic researcher from Tel Aviv University. The author has contributed to research in topics: microRNA & Exome sequencing. The author has an hindex of 49, co-authored 212 publications receiving 7442 citations. Previous affiliations of Noam Shomron include International Computer Science Institute & Massachusetts Institute of Technology.


Papers
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Journal ArticleDOI
TL;DR: It is suggested that miRNA interactions with the network of protein-coding genes evolved to buffer stochastic perturbations and thereby confer robustness to developmental genetic programs.
Abstract: Animal development is an extremely robust process resulting in stereotyped outcomes Canalization is a design principle wherein developmental pathways are stabilized to increase phenotypic reproducibility Recent revelations into microRNA (miRNA) function suggest that miRNAs act as key players in canalizing genetic programs We suggest that miRNA interactions with the network of protein-coding genes evolved to buffer stochastic perturbations and thereby confer robustness to developmental genetic programs

590 citations

Journal ArticleDOI
23 May 2003-Science
TL;DR: A mechanism that governs 3′ splice-site selection in these exons during alternative splicing is revealed, and mutations that activated the exonization of a silent intronic Alu are identified.
Abstract: Alu repetitive elements can be inserted into mature messenger RNAs via a splicing-mediated process termed exonization. To understand the molecular basis and the regulation of the process of turning intronic Alus into new exons, we compiled and analyzed a data set of human exonized Alus. We revealed a mechanism that governs 3' splice-site selection in these exons during alternative splicing. On the basis of these findings, we identified mutations that activated the exonization of a silent intronic Alu.

446 citations

Journal ArticleDOI
Catherine A. Brownstein1, Alan H. Beggs1, Nils Homer, Barry Merriman2  +207 moreInstitutions (53)
TL;DR: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases and reveals a general convergence of practices on most elements of the analysis and interpretation process.
Abstract: Background There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance.

429 citations

Journal ArticleDOI
01 Nov 2007-RNA
TL;DR: The results enable improved siRNA off-target prediction, allow integrated ranking of conserved and nonconserved miRNA targets, and show that targeting by endogenous and exogenous miRNAs/siRNAs involves similar or identical determinants.
Abstract: Vertebrate mRNAs are frequently targeted for post-transcriptional repression by microRNAs (miRNAs) through mechanisms involving pairing of 3' UTR seed matches to bases at the 5' end of miRNAs. Through analysis of expression array data following miRNA or siRNA overexpression or inhibition, we found that mRNA fold change increases multiplicatively (i.e., log-additively) with seed match count and that a single 8 mer seed match mediates down-regulation comparable to two 7 mer seed matches. We identified several targeting determinants that enhance seed match-associated mRNA repression, including the presence of adenosine opposite miRNA base 1 and of adenosine or uridine opposite miRNA base 9, independent of complementarity to the siRNA/miRNA. Increased sequence conservation in the approximately 50 bases 5' and 3' of the seed match and increased AU content 3' of the seed match were each independently associated with increased mRNA down-regulation. All of these determinants are enriched in the vicinity of conserved miRNA seed matches, supporting their activity in endogenous miRNA targeting. Together, our results enable improved siRNA off-target prediction, allow integrated ranking of conserved and nonconserved miRNA targets, and show that targeting by endogenous and exogenous miRNAs/siRNAs involves similar or identical determinants.

417 citations

Journal ArticleDOI
TL;DR: The deciphering of the pathogenesis of SAM syndrome substantiates the notion that allergy may result from a primary structural epidermal defect and is linked to a number of genes encoding allergy-related cytokines.
Abstract: The relative contribution of immunological dysregulation and impaired epithelial barrier function to allergic diseases is still a matter of debate. Here we describe a new syndrome featuring severe dermatitis, multiple allergies and metabolic wasting (SAM syndrome) caused by homozygous mutations in DSG1. DSG1 encodes desmoglein 1, a major constituent of desmosomes, which connect the cell surface to the keratin cytoskeleton and have a crucial role in maintaining epidermal integrity and barrier function. Mutations causing SAM syndrome resulted in lack of membrane expression of DSG1, leading to loss of cell-cell adhesion. In addition, DSG1 deficiency was associated with increased expression of a number of genes encoding allergy-related cytokines. Our deciphering of the pathogenesis of SAM syndrome substantiates the notion that allergy may result from a primary structural epidermal defect.

264 citations


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Journal ArticleDOI
23 Jan 2009-Cell
TL;DR: The current understanding of miRNA target recognition in animals is outlined and the widespread impact of miRNAs on both the expression and evolution of protein-coding genes is discussed.

18,036 citations

01 Jun 2012
TL;DR: SPAdes as mentioned in this paper is a new assembler for both single-cell and standard (multicell) assembly, and demonstrate that it improves on the recently released E+V-SC assembler and on popular assemblers Velvet and SoapDeNovo (for multicell data).
Abstract: The lion's share of bacteria in various environments cannot be cloned in the laboratory and thus cannot be sequenced using existing technologies. A major goal of single-cell genomics is to complement gene-centric metagenomic data with whole-genome assemblies of uncultivated organisms. Assembly of single-cell data is challenging because of highly non-uniform read coverage as well as elevated levels of sequencing errors and chimeric reads. We describe SPAdes, a new assembler for both single-cell and standard (multicell) assembly, and demonstrate that it improves on the recently released E+V-SC assembler (specialized for single-cell data) and on popular assemblers Velvet and SoapDeNovo (for multicell data). SPAdes generates single-cell assemblies, providing information about genomes of uncultivatable bacteria that vastly exceeds what may be obtained via traditional metagenomics studies. SPAdes is available online ( http://bioinf.spbau.ru/spades ). It is distributed as open source software.

10,124 citations

Journal ArticleDOI
TL;DR: This work overhauled its tool for finding preferential conservation of sequence motifs and applied it to the analysis of human 3'UTRs, increasing by nearly threefold the detected number of preferentially conserved miRNA target sites.
Abstract: MicroRNAs (miRNAs) are small endogenous RNAs that pair to sites in mRNAs to direct post-transcriptional repression. Many sites that match the miRNA seed (nucleotides 2–7), particularly those in 3 untranslated regions (3UTRs), are preferentially conserved. Here, we overhauled our tool for finding preferential conservation of sequence motifs and applied it to the analysis of human 3UTRs, increasing by nearly threefold the detected number of preferentially conserved miRNA target sites. The new tool more efficiently incorporates new genomes and more completely controls for background conservation by accounting for mutational biases, dinucleotide conservation rates, and the conservation rates of individual UTRs. The improved background model enabled preferential conservation of a new site type, the “offset 6mer,” to be detected. In total, >45,000 miRNA target sites within human 3UTRs are conserved above background levels, and >60% of human protein-coding genes have been under selective pressure to maintain pairing to miRNAs. Mammalian-specific miRNAs have far fewer conserved targets than do the more broadly conserved miRNAs, even when considering only more recently emerged targets. Although pairing to the 3 end of miRNAs can compensate for seed mismatches, this class of sites constitutes less than 2% of all preferentially conserved sites detected. The new tool enables statistically powerful analysis of individual miRNA target sites, with the probability of preferentially conserved targeting (PCT) correlating with experimental measurements of repression. Our expanded set of target predictions (including conserved 3-compensatory sites), are available at the TargetScan website, which displays the PCT for each site and each predicted target.

7,744 citations

Journal ArticleDOI
12 Aug 2015-eLife
TL;DR: It is shown that recently reported non-canonical sites do not mediate repression despite binding the miRNA, which indicates that the vast majority of functional sites are canonical.
Abstract: Proteins are built by using the information contained in molecules of messenger RNA (mRNA). Cells have several ways of controlling the amounts of different proteins they make. For example, a so-called ‘microRNA’ molecule can bind to an mRNA molecule to cause it to be more rapidly degraded and less efficiently used, thereby reducing the amount of protein built from that mRNA. Indeed, microRNAs are thought to help control the amount of protein made from most human genes, and biologists are working to predict the amount of control imparted by each microRNA on each of its mRNA targets. All RNA molecules are made up of a sequence of bases, each commonly known by a single letter—‘A’, ‘U’, ‘C’ or ‘G’. These bases can each pair up with one specific other base—‘A’ pairs with ‘U’, and ‘C’ pairs with ‘G’. To direct the repression of an mRNA molecule, a region of the microRNA known as a ‘seed’ binds to a complementary sequence in the target mRNA. ‘Canonical sites’ are regions in the mRNA that contain the exact sequence of partner bases for the bases in the microRNA seed. Some canonical sites are more effective at mRNA control than others. ‘Non-canonical sites’ also exist in which the pairing between the microRNA seed and mRNA does not completely match. Previous work has suggested that many non-canonical sites can also control mRNA degradation and usage. Agarwal et al. first used large experimental datasets from many sources to investigate microRNA activity in more detail. As expected, when mRNAs had canonical sites that matched the microRNA, mRNA levels and usage tended to drop. However, no effect was observed when the mRNAs only had recently identified non-canonical sites. This suggests that microRNAs primarily bind to canonical sites to control protein production. Based on these results, Agarwal et al. further developed a statistical model that predicts the effects of microRNAs binding to canonical sites. The updated model considers 14 different features of the microRNA, microRNA site, or mRNA—including the mRNA sequence around the site—to predict which sites within mRNAs are most effectively targeted by microRNAs. Tests showed that Agarwal et al.'s model was as good as experimental approaches at identifying the effective target sites, and was better than existing computational models. The model has been used to power the latest version of a freely available resource called TargetScan, and so could prove a valuable resource for researchers investigating the many important roles of microRNAs in controlling protein production.

5,365 citations

Journal ArticleDOI
TL;DR: This Review summarizes the current understanding of the mechanistic aspects of microRNA-induced repression of translation and discusses some of the controversies regarding different modes of micro RNA function.
Abstract: MicroRNAs constitute a large family of small, approximately 21-nucleotide-long, non-coding RNAs that have emerged as key post-transcriptional regulators of gene expression in metazoans and plants. In mammals, microRNAs are predicted to control the activity of approximately 30% of all protein-coding genes, and have been shown to participate in the regulation of almost every cellular process investigated so far. By base pairing to mRNAs, microRNAs mediate translational repression or mRNA degradation. This Review summarizes the current understanding of the mechanistic aspects of microRNA-induced repression of translation and discusses some of the controversies regarding different modes of microRNA function.

4,973 citations