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Lehner, Ben

Hyein Jang, Nicole Addy, Laura Ewing, Junia Jean-Gilles Beaubrun, YouYoung Lee, JungHa Woo, Flavia Negrete, Samantha Finkelstein, Ben D Tall, Angelika Lehner, Athmanya Eshwar, Gopal R Gopinath
Here, we present draft genome sequences of 29 Cronobacter sakazakii isolates obtained from foods of plant origin and dried-food manufacturing facilities. Assemblies and annotations resulted in genome sizes ranging from 4.3 to 4.5 Mb and 3,977 to 4,256 gene-coding sequences with G+C contents of ∼57.0%.
April 12, 2018: Genome Announcements
Gopal R Gopinath, Hannah R Chase, Jayanthi Gangiredla, Athmanya Eshwar, Hyein Jang, Isha Patel, Flavia Negrete, Samantha Finkelstein, Eunbi Park, TaeJung Chung, YeonJoo Yoo, JungHa Woo, YouYoung Lee, Jihyeon Park, Hyerim Choi, Seungeun Jeong, Soyoung Jun, Mijeong Kim, Chaeyoon Lee, HyeJin Jeong, Séamus Fanning, Roger Stephan, Carol Iversen, Felix Reich, Günter Klein, Angelika Lehner, Ben D Tall
Background: Malonate utilization, an important differential trait, well recognized as being possessed by six of the seven Cronobacter species is thought to be largely absent in Cronobacter sakazakii (Csak). The current study provides experimental evidence that confirms the presence of a malonate utilization operon in 24 strains of sequence type (ST) 64, obtained from Europe, Middle East, China, and USA; it offers explanations regarding the genomic diversity and phylogenetic relatedness among these strains, and that of other C...
2018: Gut Pathogens
Marcos Francisco Perez, Mirko Francesconi, Cristina Hidalgo-Carcedo, Ben Lehner
Genetically identical individuals that grow in the same environment often show substantial phenotypic variation within populations of organisms as diverse as bacteria, nematodes, rodents and humans. With some exceptions, the causes are poorly understood. Here we show that isogenic Caenorhabditis elegans nematodes vary in their size at hatching, speed of development, growth rate, starvation resistance, fecundity, and also in the rate of development of their germline relative to that of somatic tissues. We show that the primary cause of this variation is the age of an individual's mother, with the progeny of young mothers exhibiting several phenotypic impairments...
December 7, 2017: Nature
Andre J Faure, Jörn M Schmiedel, Ben Lehner
Isogenic cells in a common environment show substantial cell-to-cell variation in gene expression, often referred to as "expression noise." Here, we use multiple single-cell RNA-sequencing datasets to identify features associated with high or low expression noise in mouse embryonic stem cells. These include the core promoter architecture of a gene, with CpG island promoters and a TATA box associated with low and high noise, respectively. High noise is also associated with "conflicting" chromatin states-the absence of transcription-associated histone modifications or the presence of repressive ones in active genes...
November 22, 2017: Cell Systems
Adam Klosin, Kadri Reis, Cristina Hidalgo-Carcedo, Eduard Casas, Tanya Vavouri, Ben Lehner
Impaired DNA replication is a hallmark of cancer and a cause of genomic instability. We report that, in addition to causing genetic change, impaired DNA replication during embryonic development can have major epigenetic consequences for a genome. In a genome-wide screen, we identified impaired DNA replication as a cause of increased expression from a repressed transgene in Caenorhabditis elegans. The acquired expression state behaved as an "epiallele," being inherited for multiple generations before fully resetting...
August 2017: Science Advances
Hannah R Chase, Leo Eberl, Roger Stephan, HyeJin Jeong, Chaeyoon Lee, Samantha Finkelstein, Flavia Negrete, Jayanthi Gangiredla, Isha Patel, Ben D Tall, Gopal R Gopinath, Angelika Lehner
We present here the draft genome of Cronobacter sakazakii GP1999, a sequence type 145 strain isolated from the rhizosphere of tomato plants. Assembly and annotation of the genome resulted in a genome of 4,504,670 bp in size, with 4,148 coding sequences, and a GC content of 56.8%.
August 3, 2017: Genome Announcements
Fran Supek, Ben Lehner
Many processes can cause the same nucleotide change in a genome, making the identification of the mechanisms causing mutations a difficult challenge. Here, we show that clustered mutations provide a more precise fingerprint of mutagenic processes. Of nine clustered mutation signatures identified from >1,000 tumor genomes, three relate to variable APOBEC activity and three are associated with tobacco smoking. An additional signature matches the spectrum of translesion DNA polymerase eta (POLH). In lymphoid cells, these mutations target promoters, consistent with AID-initiated somatic hypermutation...
July 27, 2017: Cell
Hannah R Chase, Gopal R Gopinath, Athmanya K Eshwar, Andrea Stoller, Claudia Fricker-Feer, Jayanthi Gangiredla, Isha R Patel, Hediye N Cinar, HyeJin Jeong, ChaeYoon Lee, Flavia Negrete, Samantha Finkelstein, Roger Stephan, Ben D Tall, Angelika Lehner
Cronobacter (C.) sakazakii is an opportunistic pathogen and has been associated with serious infections with high mortality rates predominantly in pre-term, low-birth weight and/or immune compromised neonates and infants. Infections have been epidemiologically linked to consumption of intrinsically and extrinsically contaminated lots of reconstituted powdered infant formula (PIF), thus contamination of such products is a challenging task for the PIF producing industry. We present the draft genome of C. sakazakii H322, a highly persistent sequence type (ST) 83, clonal complex (CC) 65, serotype O:7 strain obtained from a batch of non-released contaminated PIF product...
2017: Frontiers in Microbiology
Adam Klosin, Eduard Casas, Cristina Hidalgo-Carcedo, Tanya Vavouri, Ben Lehner
The environment experienced by an animal can sometimes influence gene expression for one or a few subsequent generations. Here, we report the observation that a temperature-induced change in expression from a Caenorhabditis elegans heterochromatic gene array can endure for at least 14 generations. Inheritance is primarily in cis with the locus, occurs through both oocytes and sperm, and is associated with altered trimethylation of histone H3 lysine 9 (H3K9me3) before the onset of zygotic transcription. Expression profiling reveals that temperature-induced expression from endogenous repressed repeats can also be inherited for multiple generations...
April 21, 2017: Science
Tim J Stevens, David Lando, Srinjan Basu, Liam P Atkinson, Yang Cao, Steven F Lee, Martin Leeb, Kai J Wohlfahrt, Wayne Boucher, Aoife O'Shaughnessy-Kirwan, Julie Cramard, Andre J Faure, Meryem Ralser, Enrique Blanco, Lluis Morey, Miriam Sansó, Matthieu G S Palayret, Ben Lehner, Luciano Di Croce, Anton Wutz, Brian Hendrich, Dave Klenerman, Ernest D Laue
The folding of genomic DNA from the beads-on-a-string-like structure of nucleosomes into higher-order assemblies is crucially linked to nuclear processes. Here we calculate 3D structures of entire mammalian genomes using data from a new chromosome conformation capture procedure that allows us to first image and then process single cells. The technique enables genome folding to be examined at a scale of less than 100 kb, and chromosome structures to be validated. The structures of individual topological-associated domains and loops vary substantially from cell to cell...
April 6, 2017: Nature
Ben D Tall, Jayanthi Gangiredla, Christopher J Grim, Isha R Patel, Scott A Jackson, Mark K Mammel, Mahendra H Kothary, Venugopal Sathyamoorthy, Laurenda Carter, Séamus Fanning, Carol Iversen, Franco Pagotto, Roger Stephan, Angelika Lehner, Jeffery Farber, Qiong Q Yan, Gopal R Gopinath
Cronobacter (previously known as Enterobacter sakazakii) is a genus of Gram-negative, facultatively anaerobic, oxidase-negative, catalase-positive, rod-shaped bacteria of the family Enterobacteriaceae. These organisms cause a variety of illnesses such as meningitis, necrotizing enterocolitis, and septicemia in neonates and infants, and urinary tract, wound, abscesses or surgical site infections, septicemia, and pneumonia in adults. The total gene content of 379 strains of Cronobacter spp. and taxonomically-related isolates was determined using a recently reported DNA microarray...
March 4, 2017: Microarrays
Rik G H Lindeboom, Fran Supek, Ben Lehner
Premature termination codons (PTCs) cause a large proportion of inherited human genetic diseases. PTC-containing transcripts can be degraded by an mRNA surveillance pathway termed nonsense-mediated mRNA decay (NMD). However, the efficiency of NMD varies; it is inefficient when a PTC is located downstream of the last exon junction complex (EJC). We used matched exome and transcriptome data from 9,769 human tumors to systematically elucidate the rules of NMD targeting in human cells. An integrated model incorporating multiple rules beyond the canonical EJC model explains approximately three-fourths of the non-random variance in NMD efficiency across thousands of PTCs...
October 2016: Nature Genetics
Rob Jelier, Angela Kruger, Jim Swoger, Timo Zimmermann, Ben Lehner
Embryonic development must proceed despite both internal molecular fluctuations and external perturbations. However, mechanisms that provide robustness to mechanical perturbation remain largely uncharacterized. Here, we use light-sheet microscopy, comprehensive single-cell tracking, and targeted cell ablation to study the response of Caenorhabditis elegans embryos to external compression. Compression changes the relative positions of many cells and causes severe distortions of the embryonic axes. A large-scale movement of cells then corrects this distortion...
August 2016: Cell Systems
Athmanya K Eshwar, Ben D Tall, Jayanthi Gangiredla, Gopal R Gopinath, Isha R Patel, Stephan C F Neuhauss, Roger Stephan, Angelika Lehner
Bacteria belonging to the genus Cronobacter have been recognized as causative agents of life-threatening systemic infections primarily in premature, low-birth weight and immune-compromised neonates. Apparently not all Cronobacter species are linked to infantile infections and it has been proposed that virulence varies among strains. Whole genome comparisons and in silico analysis have proven to be powerful tools in elucidating potential virulence determinants, the presence/absence of which may explain the differential virulence behaviour of strains...
2016: PloS One
Ara Cho, Jung Eun Shim, Eiru Kim, Fran Supek, Ben Lehner, Insuk Lee
A major challenge for distinguishing cancer-causing driver mutations from inconsequential passenger mutations is the long-tail of infrequently mutated genes in cancer genomes. Here, we present and evaluate a method for prioritizing cancer genes accounting not only for mutations in individual genes but also in their neighbors in functional networks, MUFFINN (MUtations For Functional Impact on Network Neighbors). This pathway-centric method shows high sensitivity compared with gene-centric analyses of mutation data...
June 23, 2016: Genome Biology
Benedetta Bolognesi, Nieves Lorenzo Gotor, Riddhiman Dhar, Davide Cirillo, Marta Baldrighi, Gian Gaetano Tartaglia, Ben Lehner
Multiple human diseases are associated with a liquid-to-solid phase transition resulting in the formation of amyloid fibers or protein aggregates. Here, we present an alternative mechanism for cellular toxicity based on a concentration-dependent liquid-liquid demixing. Analyzing proteins that are toxic when their concentration is increased in yeast reveals that they share physicochemical properties with proteins that participate in physiological liquid-liquid demixing in the cell. Increasing the concentration of one of these proteins indeed results in the formation of cytoplasmic foci with liquid properties...
June 28, 2016: Cell Reports
Philippe Julien, Belén Miñana, Pablo Baeza-Centurion, Juan Valcárcel, Ben Lehner
The properties of genotype-phenotype landscapes are crucial for understanding evolution but are not characterized for most traits. Here, we present a >95% complete local landscape for a defined molecular function-the alternative splicing of a human exon (FAS/CD95 exon 6, involved in the control of apoptosis). The landscape provides important mechanistic insights, revealing that regulatory information is dispersed throughout nearly every nucleotide in an exon, that the exon is more robust to the effects of mutations than its immediate neighbours in genotype space, and that high mutation sensitivity (evolvability) will drive the rapid divergence of alternative splicing between species unless it is constrained by selection...
May 10, 2016: Nature Communications
Adam Klosin, Ben Lehner
Development never starts from a blank slate of DNA. Therefore, in principle, plenty beyond DNA could transmit phenotypic information from one generation to the next. However, the extent to which epigenetic information is actually transmitted between generations and whether this information is modulated by the environment are questions that have only recently started to be investigated at the molecular level. Here we review molecular work on inter-generation epigenetic effects in animals and highlight some principles of epigenetic transmission...
February 2016: Current Opinion in Genetics & Development
Mirko Francesconi, Ben Lehner
Genome-wide gene expression profiling is a fast, cheap and standardised analysis that provides a high dimensional measurement of the state of a biological sample. In this review we describe computational methods that can be applied to identify and interpret sources of variance in gene expression in whole organisms, organs, tissues or single cells. This allows the identification of constituent cell types and states in complex mixtures, the reconstruction of temporal trajectories of development, differentiation and progression, and the reconstruction of spatial patterning...
October 2015: Molecular BioSystems
David van Dijk, Riddhiman Dhar, Alsu M Missarova, Lorena Espinar, William R Blevins, Ben Lehner, Lucas B Carey
Isogenic cells show a large degree of variability in growth rate, even when cultured in the same environment. Such cell-to-cell variability in growth can alter sensitivity to antibiotics, chemotherapy and environmental stress. To characterize transcriptional differences associated with this variability, we have developed a method--FitFlow--that enables the sorting of subpopulations by growth rate. The slow-growing subpopulation shows a transcriptional stress response, but, more surprisingly, these cells have reduced RNA polymerase fidelity and exhibit a DNA damage response...
August 13, 2015: Nature Communications
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