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UTAP: User-friendly Transcriptome Analysis Pipeline

Refael Kohen, Jonathan Barlev, Gil Hornung, Gil Stelzer, Ester Feldmesser, Kiril Kogan, Marilyn Safran, Dena Leshkowitz
2019 BMC Bioinformatics  
RNA-Seq technology is routinely used to characterize the transcriptome, and to detect gene expression differences among cell types, genotypes and conditions. Advances in short-read sequencing instruments such as Illumina Next-Seq have yielded easy-to-operate machines, with high throughput, at a lower price per base. However, processing this data requires bioinformatics expertise to tailor and execute specific solutions for each type of library preparation. Results: In order to enable fast and
more » ... er-friendly data analysis, we developed an intuitive and scalable transcriptome pipeline that executes the full process, starting from cDNA sequences derived by RNA-Seq [Nat Rev Genet 10:57-63, 2009] and bulk MARS-Seq [Science 343:776-779, 2014] and ending with sets of differentially expressed genes. Output files are placed in structured folders, and results summaries are provided in rich and comprehensive reports, containing dozens of plots, tables and links. Conclusion: Our User-friendly Transcriptome Analysis Pipeline (UTAP) is an open source, web-based intuitive platform available to the biomedical research community, enabling researchers to efficiently and accurately analyse transcriptome sequence data.
doi:10.1186/s12859-019-2728-2 fatcat:6ytquwm2nbgmzntbiknqaluaei

Integration of stress signals by homeodomain interacting protein kinases

Michael Lienhard Schmitz, Alfonso Rodriguez-Gil, Juliane Hornung
2014 Biological chemistry  
AbstractThe family of homeodomain interacting protein kinases (HIPKs) consists of four related kinases, HIPK1 to HIPK4. These serine/threonine kinases are evolutionary conserved and derive from the yeast kinase Yak1. The largest group of HIPK phosphorylation substrates is represented by transcription factors and chromatin-associated regulators of gene expression, thus transferring HIPK-derived signals into changes of gene expression programs. The HIPKs mainly function as regulators of
more » ... tal processes and as integrators of a wide variety of stress signals. A number of conditions representing precarious situations, such as DNA damage, hypoxia, reactive oxygen intermediates and metabolic stress affect the function of HIPKs. The kinases function as integrators for these stress signals and feed them into many different downstream effector pathways that serve to cope with these precarious situations. HIPKs do not function as essential core components in the different stress signaling pathways, but rather serve as modulators of signal output and as connectors of different stress signaling pathways. Their central role as signaling hubs with the ability to shape many downstream effector pathways frequently implies them in proliferative diseases such as cancer or fibrosis.
doi:10.1515/hsz-2013-0264 pmid:24225127 fatcat:36iio4mv4fbddatgtgdtdgt2ku

Expression Noise and Acetylation Profiles Distinguish HDAC Functions

Leehee Weinberger, Yoav Voichek, Itay Tirosh, Gil Hornung, Ido Amit, Naama Barkai
2012 Molecular Cell  
doi:10.1016/j.molcel.2012.05.008 pmid:22683268 pmcid:PMC3408861 fatcat:m47x4xgttvem5kibui34jysoty

Morphogen gradient formation in a complex environment: An anomalous diffusion model

Gil Hornung, Brian Berkowitz, Naama Barkai
2005 Physical Review E  
Current models of morphogen-induced patterning assume that morphogens undergo normal, or Fickian, diffusion, although the validity of this assumption has never been examined. Here we argue that the interaction of morphogens with the complex extracellular surrounding may lead to anomalous diffusion. We present a phenomenological model that captures this interaction, and derive the properties of the morphogen profile under conditions of anomalous ͑non-Fickian͒ diffusion. In this context we
more » ... r the continuous time random walk formalism and extend its application to account for degradation of morphogen particles. We show that within the anomalous diffusion model, morphogen profiles are fundamentally distinct from the corresponding Fickian profiles. Differences were found in several key aspects, including the role of degradation in determining the profile, the rate by which it spreads in time and its long-term behavior. We analyze the effect of an abrupt change in the extracellular environment on the concentration profiles. Furthermore, we discuss the robustness of the morphogen distribution to fluctuations in morphogen production rate, and describe a feedback mechanism that can buffer such fluctuations. Our study also provides rigorous criteria to distinguish experimentally between Fickian and anomalous modes of morphogen transport.
doi:10.1103/physreve.72.041916 pmid:16383429 fatcat:opxjq7bywvas7f3zduvyn6fc5m

Promoter Nucleosome Organization Shapes the Evolution of Gene Expression

Dalia Rosin, Gil Hornung, Itay Tirosh, Ariel Gispan, Naama Barkai, Hiten D. Madhani
2012 PLoS Genetics  
Understanding why genes evolve at different rates is fundamental to evolutionary thinking. In species of the budding yeast, the rate at which genes diverge in expression correlates with the organization of their promoter nucleosomes: genes lacking a nucleosome-free region (denoted OPN for "Occupied Proximal Nucleosomes") vary widely between the species, while the expression of those containing NFR (denoted DPN for "Depleted Proximal Nucleosomes") remains largely conserved. To examine if early
more » ... olutionary dynamics contributes to this difference in divergence, we artificially selected for high expression of GFP-fused proteins. Surprisingly, selection was equally successful for OPN and DPN genes, with ,80% of genes in each group stably increasing in expression by a similar amount. Notably, the two groups adapted by distinct mechanisms: DPN-selected strains duplicated large genomic regions, while OPN-selected strains favored trans mutations not involving duplications. When selection was removed, DPN (but not OPN) genes reverted rapidly to wild-type expression levels, consistent with their lower diversity between species. Our results suggest that promoter organization constrains the early evolutionary dynamics and in this way biases the path of long-term evolution.
doi:10.1371/journal.pgen.1002579 pmid:22438828 pmcid:PMC3305400 fatcat:2shzuuk5evap5pfj6nqkq34rrq

Noise propagation and signaling sensitivity in biological networks: A role for positive feedback

Gil Hornung, Naama Barkai
2005 PLoS Computational Biology  
Citation: Hornung G, Barkai N (2008) Noise propagation and signaling sensitivity in biological networks: A role for positive feedback. PLoS Comput Biol 4(1): e8.  ... 
doi:10.1371/journal.pcbi.0040008.eor fatcat:ygkfze6nzbha7jn34k37rtyydm

Noise Propagation and Signaling Sensitivity in Biological Networks: A Role for Positive Feedback

Gil Hornung, Naama Barkai
2008 PLoS Computational Biology  
Citation: Hornung G, Barkai N (2008) Noise propagation and signaling sensitivity in biological networks: A role for positive feedback. PLoS Comput Biol 4(1): e8.  ... 
doi:10.1371/journal.pcbi.0040008 pmid:18179281 pmcid:PMC2174979 fatcat:nev2jhjkajfjlfuwuzcju3tbgu

Navigation in three-dimensional cluttered environments for mobile manipulation

Armin Hornung, Mike Phillips, E. Gil Jones, Maren Bennewitz, Maxim Likhachev, Sachin Chitta
2012 2012 IEEE International Conference on Robotics and Automation  
Hornung and M. Bennewitz are with the Humanoid Robots Lab, University of Freiburg, Germany. M. Phillips and M. Likhachev are with the  ...  Hornung and Bennewitz [6] recently proposed an approach for efficient humanoid robot navigation by combining coarse 2D path planning in open spaces and detailed footstep planning in the vicinity of obstacles  ... 
doi:10.1109/icra.2012.6225029 dblp:conf/icra/HornungPJBLC12 fatcat:ykyxxuhxxnhx7lyha6qthzymua

High Expression of CD200 and CD200R1 Distinguishes Stem and Progenitor Cell Populations within Mammary Repopulating Units

Gat Rauner, Tania Kudinov, Shlomit Gilad, Gil Hornung, Itamar Barash
2018 Stem Cell Reports  
Aiming to unravel the top of the mammary epithelial cell hierarchy, a subset of the CD49f high CD24 med mammary repopulating units (MRUs) was identified by flow cytometry, expressing high levels of CD200 and its receptor CD200R1. These MRU CD200/CD200R1 repopulated a larger area of de-epithelized mammary fat pads than the rest of the MRUs, termed MRU not CD200/CD200R1 . MRU CD200/CD200R1 maintained a much lower number of divergently defined, highly expressed genes and pathways that support
more » ... r cell growth, development, differentiation, and progenitor activity than their MRU not CD200/CD200R1 counterparts. A defined profile of hierarchically associated genes supporting a single-lineage hypothesis was confirmed by in vitro mammosphere analysis that assembled 114 genes with decreased expression from MRU CD200/CD200R1 via MRU not CD200/CD200R1 toward CD200 + CD200R1 À and CD200R1 + CD200 À cells. About 40% of these genes were shared by a previously published database of upregulated genes in mammary/breast stem cells and may represent the core genes involved in mammary stemness.
doi:10.1016/j.stemcr.2018.05.013 pmid:29937142 pmcid:PMC6067058 fatcat:zjce76acbne23fhmxzdkjdprhy

Genetic variation in the emblematic Puya raimondii (Bromeliaceae) from Huascarán National Park, Peru

Claudia Teresa Hornung-Leoni, Victoria Sosa, June Simpson, Katia Gil
2013 Crop Breeding and Applied Biotechnology  
Plants take from 40 to 100 years to flower (Benzing 2000, Hornung-Leoni and Sosa 2004) .  ...  Both localities are separated by 300 km.CT Hornung-Leoni et al. Figure 3 . 3 Plot of the individuals of the first two axes of the PCoA.  ... 
doi:10.1590/s1984-70332013000100008 fatcat:vuqsqho5ifcwtmxn64wezkvalq

Experimental Evolution of Bacillus subtilis Reveals the Evolutionary Dynamics of Horizontal Gene Transfer and Suggests Adaptive and Neutral Effects

Shai Slomka, Itamar Françoise, Gil Hornung, Omer Asraf, Tammy Biniashvili, Yitzhak Pilpel, Orna Dahan
2020 Genetics  
Tracing evolutionary processes that lead to fixation of genomic variation in wild bacterial populations is a prime challenge in molecular evolution. In particular, the relative contribution of Horizontal Gene Transfer (HGT) versus de novo mutations during adaptation to a new environment is poorly understood. To gain a better understanding of the dynamics of HGT and its effect on adaptation, we subjected several populations of competent Bacillus subtilis to a serial dilution evolution on a high
more » ... alt containing medium, either with or without foreign DNA from diverse pre-adapted or naturally salt tolerant species. Following 504 generations of evolution, all populations improved growth yield on the medium. Sequencing of evolved populations revealed extensive acquisition of foreign DNA from close Bacillus donors but not from more remote donors. HGT occurred in bursts, whereby a single bacterial cell appears to have acquired dozens of fragments at once. In the largest burst, close to 2% of the genome has been replaced by HGT. Acquired segments tend to be clustered in integration "hot spots". Other than HGT, genomes also acquired spontaneous mutations. Many of these mutations occurred within, and seem to alter, the sequence of flagellar proteins. Finally, we show that while some HGT fragments could be neutral, others are adaptive and accelerate evolution.
doi:10.1534/genetics.120.303401 pmid:32847815 pmcid:PMC7536860 fatcat:rged3z3k3rc3zlibgf7tyuiu34

HIPK family kinases bind and regulate the function of the CCR4-NOT complex

Alfonso Rodriguez-Gil, Olesja Ritter, Juliane Hornung, Hilda Stekman, Marcus Krüger, Thomas Braun, Elisabeth Kremmer, Michael Kracht, M. Lienhard Schmitz, Anne Spang
2016 Molecular Biology of the Cell  
., Hornung, J., Kremmer, E., Milanovic, M., and Schmitz, M.L. (2013) .  ... 
doi:10.1091/mbc.e15-09-0629 pmid:27122605 pmcid:PMC4907730 fatcat:mxxuordofndpfd6mepbaixs2iq

Codon usage of highly expressed genes affects proteome-wide translation efficiency

Idan Frumkin, Marc J. Lajoie, Christopher J. Gregg, Gil Hornung, George M. Church, Yitzhak Pilpel
2018 Proceedings of the National Academy of Sciences of the United States of America  
Although the genetic code is redundant, synonymous codons for the same amino acid are not used with equal frequencies in genomes, a phenomenon termed "codon usage bias." Previous studies have demonstrated that synonymous changes in a coding sequence can exert significant cis effects on the gene's expression level. However, whether the codon composition of a gene can also affect the translation efficiency of other genes has not been thoroughly explored. To study how codon usage bias influences
more » ... e cellular economy of translation, we massively converted abundant codons to their rare synonymous counterpart in several highly expressed genes in Escherichia coli. This perturbation reduces both the cellular fitness and the translation efficiency of genes that have high initiation rates and are naturally enriched with the manipulated codon, in agreement with theoretical predictions. Interestingly, we could alleviate the observed phenotypes by increasing the supply of the tRNA for the highly demanded codon, thus demonstrating that the codon usage of highly expressed genes was selected in evolution to maintain the efficiency of global protein translation. codon usage evolution | tRNA | codon-to-tRNA balance | translation efficiency | genome engineering S ince there are 61 sense codons but only 20 amino acids, most amino acids are encoded by more than a single codon. However, synonymous codons for the same amino acid are not utilized to the same extent across different genes or genomes. This phenomenon, termed "codon usage bias," has been the subject of intense research and was shown to affect gene expression and cellular function through varied processes in bacteria, yeast, and mammals (1-4). Although differential codon usage can result from neutral processes of mutational biases and drift (5-7), certain codon choices could be specifically favored as they increase the efficiency (8-12) or accuracy (13-17) of protein synthesis. These forces would typically lead to codon biases in a gene because they locally exert their effect on the gene in which the codons reside. Indeed, there is a positive correlation between a gene's expression level and the degree of its codon bias (1). Various systems have demonstrated how altering the codon usage synonymously can alter the expression levels of the manipulated genes (18-21), an effect that could reach more than 1,000-fold (22). In addition to such cis effects, it is possible that codon usage also acts in trans, namely, that the codon choice of some genes would affect the translation of others due to a "shared economy" of the entire translation apparatus (23-25). Previous theoretical works have suggested that an increase in the elongation rate may reduce the number of ribosomes on mRNAs and therefore may indirectly increase the rate of initiation of other transcripts due to an increase in the pool of free ribosomes (6, 26). In addition, a recent computational study in yeast has also examined the indirect effects of synonymous codon changes on the translation of the entire transcriptome (27). However, experimental evidence of such changes is absent. Here we ask how manipulating the frequency of a single codon on a small subset of genes influences the synthesis of other proteins. To tackle this question, we replaced common codons with a synonymous, rare counterpart in several highly expressed genes. We then asked how this massive change in the codon representation in the transcriptome would affect the manipulated genes, other genes, and the physiology and well-being of the cell (Fig. 1) . Interestingly, our genetic manipulation did not consistently affect the translation efficiency of the mutated genes, but it did show a profound proteome-wide effect on the translation process. Importantly, the translation efficiency of genes changed in a way that was dependent on the extent to which they contained the affected codons. These observations demonstrate that trans effects of codon usage could have strong implications in the cell. We could alleviate these physiological and molecular defects by increasing the tRNA supply for the manipulated codon in a manner that restored codon-to-tRNA balance. Our work demonstrates that codon choice not only tunes the expression level of individual genes but also maintains the efficiency of global protein translation in the cell.
doi:10.1073/pnas.1719375115 pmid:29735666 fatcat:7uyxypjapjfanj2v7hmc3c7iii

Human RIPK1 deficiency causes combined immunodeficiency and inflammatory bowel diseases

Yue Li, Marita Führer, Ehsan Bahrami, Piotr Socha, Maja Klaudel-Dreszler, Amira Bouzidi, Yanshan Liu, Anna S. Lehle, Thomas Magg, Sebastian Hollizeck, Meino Rohlfs, Raffaele Conca (+24 others)
2018 Proceedings of the National Academy of Sciences of the United States of America  
Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) is a critical regulator of cell death and inflammation, but its relevance for human disease pathogenesis remains elusive. Studies of monogenic disorders might provide critical insights into disease mechanisms and therapeutic targeting of RIPK1 for common diseases. Here, we report on eight patients from six unrelated pedigrees with biallelic loss-of-function mutations in RIPK1 presenting with primary immunodeficiency and/or
more » ... inflammation. Mutations in RIPK1 were associated with reduced NF-κB activity, defective differentiation of T and B cells, increased inflammasome activity, and impaired response to TNFR1-mediated cell death in intestinal epithelial cells. The characterization of RIPK1-deficient patients highlights the essential role of RIPK1 in controlling human immune and intestinal homeostasis, and might have critical implications for therapies targeting RIPK1.
doi:10.1073/pnas.1813582116 pmid:30591564 pmcid:PMC6338855 fatcat:35mfyud765bqnjcao4gpquysmu

Page 392 of Munsey's Magazine Vol. 49, Issue 3 [page]

1913 Munsey's Magazine  
Hornung and “ The Adventures of Miss Gregory” of Mr. Perceval Gibbon. The pair which are native to our own soil are “Scientific Sprague,” by Mr.  ...  He might even be persistent enough to insist that the same device could be dis- covered in the “Gil Blas” of Le Sage, the successive parts of which were first pub- lished intermittently after intervals  ... 
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