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Eran segal

David van Dijk, Eilon Sharon, Maya Lotan-Pompan, Adina Weinberger, Eran Segal, Lucas B Carey
No abstract text is available yet for this article.
March 2017: Genome Research
Michal Levo, Tali Avnit-Sagi, Maya Lotan-Pompan, Yael Kalma, Adina Weinberger, Zohar Yakhini, Eran Segal
Precise gene expression patterns are established by transcription factor (TFs) binding to regulatory sequences. While these events occur in the context of chromatin, our understanding of how TF-nucleosome interplay affects gene expression is highly limited. Here, we present an assay for high-resolution measurements of both DNA occupancy and gene expression on large-scale libraries of systematically designed regulatory sequences. Our assay reveals occupancy patterns at the single-cell level. It provides an accurate quantification of the fraction of the population bound by a nucleosome and captures distinct, even adjacent, TF binding events...
February 16, 2017: Molecular Cell
David van Dijk, Eilon Sharon, Maya Lotan-Pompan, Adina Weinberger, Eran Segal, Lucas B Carey
Transcription factors (TFs) are key mediators that propagate extracellular and intracellular signals through to changes in gene expression profiles. However, the rules by which promoters decode the amount of active TF into target gene expression are not well understood. To determine the mapping between promoter DNA sequence, TF concentration, and gene expression output, we have conducted in budding yeast a large-scale measurement of the activity of thousands of designed promoters at six different levels of TF...
January 2017: Genome Research
Christoph A Thaiss, Maayan Levy, Tal Korem, Lenka Dohnalová, Hagit Shapiro, Diego A Jaitin, Eyal David, Deborah R Winter, Meital Gury-BenAri, Evgeny Tatirovsky, Timur Tuganbaev, Sara Federici, Niv Zmora, David Zeevi, Mally Dori-Bachash, Meirav Pevsner-Fischer, Elena Kartvelishvily, Alexander Brandis, Alon Harmelin, Oren Shibolet, Zamir Halpern, Kenya Honda, Ido Amit, Eran Segal, Eran Elinav
The intestinal microbiota undergoes diurnal compositional and functional oscillations that affect metabolic homeostasis, but the mechanisms by which the rhythmic microbiota influences host circadian activity remain elusive. Using integrated multi-omics and imaging approaches, we demonstrate that the gut microbiota features oscillating biogeographical localization and metabolome patterns that determine the rhythmic exposure of the intestinal epithelium to different bacterial species and their metabolites over the course of a day...
December 1, 2016: Cell
Christoph A Thaiss, Shlomik Itav, Daphna Rothschild, Mariska Meijer, Maayan Levy, Claudia Moresi, Lenka Dohnalová, Sofia Braverman, Shachar Rozin, Sergey Malitsky, Mally Dori-Bachash, Yael Kuperman, Inbal Biton, Arieh Gertler, Alon Harmelin, Hagit Shapiro, Zamir Halpern, Asaph Aharoni, Eran Segal, Eran Elinav
In tackling the obesity pandemic, significant efforts are devoted to the development of effective weight reduction strategies, yet many dieting individuals fail to maintain a long-term weight reduction, and instead undergo excessive weight regain cycles. The mechanisms driving recurrent post-dieting obesity remain largely elusive. Here, we identify an intestinal microbiome signature that persists after successful dieting of obese mice, which contributes to faster weight regain and metabolic aberrations upon re-exposure to obesity-promoting conditions and transmits the accelerated weight regain phenotype upon inter-animal transfer...
November 24, 2016: Nature
Leeat Keren, Jean Hausser, Maya Lotan-Pompan, Ilya Vainberg Slutskin, Hadas Alisar, Sivan Kaminski, Adina Weinberger, Uri Alon, Ron Milo, Eran Segal
Data of gene expression levels across individuals, cell types, and disease states is expanding, yet our understanding of how expression levels impact phenotype is limited. Here, we present a massively parallel system for assaying the effect of gene expression levels on fitness in Saccharomyces cerevisiae by systematically altering the expression level of ∼100 genes at ∼100 distinct levels spanning a 500-fold range at high resolution. We show that the relationship between expression levels and growth is gene and environment specific and provides information on the function, stoichiometry, and interactions of genes...
August 25, 2016: Cell
Lik Hang Lee, Marcela S Cavalcanti, Neil H Segal, Jaclyn F Hechtman, Martin R Weiser, J Joshua Smith, Julio Garcia-Aguilar, Eran Sadot, Peter Ntiamoah, Arnold J Markowitz, Moshe Shike, Zsofia K Stadler, Efsevia Vakiani, David S Klimstra, Jinru Shia
Immune checkpoint blockade targeting the programmed death-1 (PD-1) pathway has shown efficacy in several types of cancers including mismatch-repair-deficient colorectal carcinoma. In some tumor types, programmed death-ligand 1 (PD-L1) expression detected by immunohistochemistry has shown utility as a predictive marker for response to anti-PD-1 therapies. This utility, however, remains to be determined in colorectal carcinoma. In addition, although tumor-infiltrating lymphocytes have been associated with better prognosis in colorectal carcinoma, the prognostic value of PD-1 expression in these lymphocytes and its interaction with PD-L1 expression still await investigation...
November 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Shira Weingarten-Gabbay, Eran Segal
Translational regulation is a critical step in the production of proteins from genomic material in both human and viruses. However, unlike other steps of the central dogma, such as transcriptional regulation, little is known about the cis-regulatory elements involved. In a recent study we devised a high-throughput bicistronic reporter assay for the discovery and the characterization of thousands of novel Internal Ribosome Entry Sites (IRESs) in human and hundreds of viral genomes. Our results provide insights into the landscape of IRES elements in human and viral transcripts and the cis-regulatory sequences underlying their activity...
October 2, 2016: RNA Biology
Uri Barenholz, Leeat Keren, Eran Segal, Ron Milo
Most proteins show changes in level across growth conditions. Many of these changes seem to be coordinated with the specific growth rate rather than the growth environment or the protein function. Although cellular growth rates, gene expression levels and gene regulation have been at the center of biological research for decades, there are only a few models giving a base line prediction of the dependence of the proteome fraction occupied by a gene with the specific growth rate. We present a simple model that predicts a widely coordinated increase in the fraction of many proteins out of the proteome, proportionally with the growth rate...
2016: PloS One
David Zeevi, Tal Korem, Eran Segal
A report on the first EMBO conference entitled "Next Gen Immunology-From Host Genome to the Microbiome: Immunity in the Genomic Era", held at the Weizmann Institute of Science, Israel, 14-16 February, 2016.
March 17, 2016: Genome Biology
Shira Weingarten-Gabbay, Shani Elias-Kirma, Ronit Nir, Alexey A Gritsenko, Noam Stern-Ginossar, Zohar Yakhini, Adina Weinberger, Eran Segal
To investigate gene specificity at the level of translation in both the human genome and viruses, we devised a high-throughput bicistronic assay to quantify cap-independent translation. We uncovered thousands of novel cap-independent translation sequences, and we provide insights on the landscape of translational regulation in both humans and viruses. We find extensive translational elements in the 3' untranslated region of human transcripts and the polyprotein region of uncapped RNA viruses. Through the characterization of regulatory elements underlying cap-independent translation activity, we identify potential mechanisms of secondary structure, short sequence motif, and base pairing with the 18S ribosomal RNA (rRNA)...
January 15, 2016: Science
Kun Qu, Sara Garamszegi, Felix Wu, Helga Thorvaldsdottir, Ted Liefeld, Marco Ocana, Diego Borges-Rivera, Nathalie Pochet, James T Robinson, Barry Demchak, Tim Hull, Gil Ben-Artzi, Daniel Blankenberg, Galt P Barber, Brian T Lee, Robert M Kuhn, Anton Nekrutenko, Eran Segal, Trey Ideker, Michael Reich, Aviv Regev, Howard Y Chang, Jill P Mesirov
Complex biomedical analyses require the use of multiple software tools in concert and remain challenging for much of the biomedical research community. We introduce GenomeSpace (, a cloud-based, cooperative community resource that currently supports the streamlined interaction of 20 bioinformatics tools and data resources. To facilitate integrative analysis by non-programmers, it offers a growing set of 'recipes', short workflows to guide investigators through high-utility analysis tasks...
March 2016: Nature Methods
Niv Zmora, David Zeevi, Tal Korem, Eran Segal, Eran Elinav
The genomic revolution enabled the clinical inclusion of an immense body of person-specific information to an extent that is revolutionizing medicine and science. The gut microbiome, our "second genome," dynamically integrates signals from the host and its environment, impacting health and risk of disease. Herein, we summarize how individualized characterization of the microbiome composition and function may assist in personalized diagnostic assessment, risk stratification, disease prevention, treatment decision-making, and patients' follow up...
January 13, 2016: Cell Host & Microbe
Maayan Levy, Christoph A Thaiss, David Zeevi, Lenka Dohnalová, Gili Zilberman-Schapira, Jemal Ali Mahdi, Eyal David, Alon Savidor, Tal Korem, Yonatan Herzig, Meirav Pevsner-Fischer, Hagit Shapiro, Anette Christ, Alon Harmelin, Zamir Halpern, Eicke Latz, Richard A Flavell, Ido Amit, Eran Segal, Eran Elinav
Host-microbiome co-evolution drives homeostasis and disease susceptibility, yet regulatory principles governing the integrated intestinal host-commensal microenvironment remain obscure. While inflammasome signaling participates in these interactions, its activators and microbiome-modulating mechanisms are unknown. Here, we demonstrate that the microbiota-associated metabolites taurine, histamine, and spermine shape the host-microbiome interface by co-modulating NLRP6 inflammasome signaling, epithelial IL-18 secretion, and downstream anti-microbial peptide (AMP) profiles...
December 3, 2015: Cell
David Zeevi, Tal Korem, Niv Zmora, David Israeli, Daphna Rothschild, Adina Weinberger, Orly Ben-Yacov, Dar Lador, Tali Avnit-Sagi, Maya Lotan-Pompan, Jotham Suez, Jemal Ali Mahdi, Elad Matot, Gal Malka, Noa Kosower, Michal Rein, Gili Zilberman-Schapira, Lenka Dohnalová, Meirav Pevsner-Fischer, Rony Bikovsky, Zamir Halpern, Eran Elinav, Eran Segal
Elevated postprandial blood glucose levels constitute a global epidemic and a major risk factor for prediabetes and type II diabetes, but existing dietary methods for controlling them have limited efficacy. Here, we continuously monitored week-long glucose levels in an 800-person cohort, measured responses to 46,898 meals, and found high variability in the response to identical meals, suggesting that universal dietary recommendations may have limited utility. We devised a machine-learning algorithm that integrates blood parameters, dietary habits, anthropometrics, physical activity, and gut microbiota measured in this cohort and showed that it accurately predicts personalized postprandial glycemic response to real-life meals...
November 19, 2015: Cell
Leeat Keren, David van Dijk, Shira Weingarten-Gabbay, Dan Davidi, Ghil Jona, Adina Weinberger, Ron Milo, Eran Segal
Genetically identical cells exposed to the same environment display variability in gene expression (noise), with important consequences for the fidelity of cellular regulation and biological function. Although population average gene expression is tightly coupled to growth rate, the effects of changes in environmental conditions on expression variability are not known. Here, we measure the single-cell expression distributions of approximately 900 Saccharomyces cerevisiae promoters across four environmental conditions using flow cytometry, and find that gene expression noise is tightly coupled to the environment and is generally higher at lower growth rates...
December 2015: Genome Research
Michal Levo, Einat Zalckvar, Eilon Sharon, Ana Carolina Dantas Machado, Yael Kalma, Maya Lotan-Pompan, Adina Weinberger, Zohar Yakhini, Remo Rohs, Eran Segal
No abstract text is available yet for this article.
September 2015: Genome Research
Tal Korem, David Zeevi, Jotham Suez, Adina Weinberger, Tali Avnit-Sagi, Maya Pompan-Lotan, Elad Matot, Ghil Jona, Alon Harmelin, Nadav Cohen, Alexandra Sirota-Madi, Christoph A Thaiss, Meirav Pevsner-Fischer, Rotem Sorek, Ramnik J Xavier, Eran Elinav, Eran Segal
Metagenomic sequencing increased our understanding of the role of the microbiome in health and disease, yet it only provides a snapshot of a highly dynamic ecosystem. Here, we show that the pattern of metagenomic sequencing read coverage for different microbial genomes contains a single trough and a single peak, the latter coinciding with the bacterial origin of replication. Furthermore, the ratio of sequencing coverage between the peak and trough provides a quantitative measure of a species' growth rate. We demonstrate this in vitro and in vivo, under different growth conditions, and in complex bacterial communities...
September 4, 2015: Science
Gad Estis, Eran Segal
Obesity has become a "global pandemic" in the modern world. One of the anesthetic challenges associated with obesity is securing the patients' airway. It is well known that obese patients have a higher complication rate during anesthesia as compared to patients with normal weight, but the reasons for this are controversial. Although obesity in itself does not pose a problem during anesthesia, several types of obesity, specifically the central (abdominal, visceral, android or apple-shaped) obesity, the type which is often called "inflated bear" type, cause more difficulty in maintaining open airways during the various stages of anesthesia, particularly during induction...
April 2015: Harefuah
Eran Segal, Michael Millgram, Sigal Tal, Vladimir Karaiev, Ely Ashkenazi
Spinal anesthesia and lumbar puncture may lead to intracerebral, subdural or subarachnoid bleeding and there have been previous reports on patients who developed subdural hematoma a few days after surgery on the spine. This is a case report of a patient who developed acute subdural hematoma during surgery performed to remove an intradural spine tumor. This report suggests that the possibility of an intracranial hematoma should be considered in cases of neurological deterioration following spinal surgery.
April 2015: Harefuah
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