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1. Metabolic stress in space: ROS-induced mutations in mice hint at a new path to cancer

Author

Viktor Stolc, Miloslav Karhanek, Friedemann Freund, Yuri Griko, David J. Loftus, and Maurice M. Ohayon

Subjects
Medicine (General), R5-920, Biology (General), QH301-705.5
Abstract

Long-duration spaceflight beyond Earth's magnetosphere poses serious health risks, including muscle atrophy, bone loss, liver and kidney damage, and the Spaceflight-Associated Neuro-ocular Syndrome (SANS). RNA-seq of mice aboard the International Space Station (ISS) for 37 days revealed extraordinary hypermutation in tissue-specific genes, with guanine base conversion predominating, potentially contributing to spaceflight-associated health risks. Our results suggest that the genome-wide accelerated mutation that we measured, seemingly independent of radiation dose, was induced by oxidative damage from higher atmospheric carbon dioxide (CO2) levels and increased reactive oxygen species (ROS) on the ISS. This accelerated mutation, faster via RNA transcription than replication and more numerous than by radiation alone, unveils novel hotspots in the mammalian proteome. Notably, these hotspots correlate with commonly mutated genes across various human cancers, highlighting the ISS as a crucial platform for studying accelerated mutation, genome instability, and the induction of disease-causing mutations in model organisms. Our results suggest that metabolic processes can contribute to somatic mutation, and thus may play a role in the development of cancer. A metabolic link to genetic instability potentially has far-reaching implications for various diseases, with implications for human health on Earth and in space.

Published
2024
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2. Time resolved DNA occupancy dynamics during the respiratory oscillation uncover a global reset point in the yeast growth program

Author

Cornelia Amariei, Rainer Machné, Viktor Stolc, Tomoyoshi Soga, Masaru Tomita, and Douglas B. Murray

Subjects
respiratory oscillation, chromatin dynamics, transcription regulation, histone modification, anabolism, catabolism, energetics, Biology (General), QH301-705.5
Abstract

The structural dynamics of chromatin have been implicated in the regulation of fundamental eukaryotic processes, such as DNA transcription, replication and repair. Although previous studies have revealed that the chromatin landscape, nucleosome remodeling and histone modification events are intimately tied into cellular energetics and redox state, few studies undertake defined time-resolved measurements of these state variables. Here, we use metabolically synchronous, continuously-grown yeast cultures to measure DNA occupancy and track global patterns with respect to the metabolic state of the culture. Combined with transcriptome analyses and ChIP-qPCR experiments, these paint an intriguing picture where genome-wide nucleosome focusing occurs during the recovery of energy charge, followed by clearance of the promoter regions and global transcriptional slow-down, thus indicating a nucleosome-mediated “reset point” for the cycle. The reset begins at the end of the catabolic and stress-response transcriptional programs and ends prior to the start of the anabolic and cell-growth transcriptional program, and the histones on genes from both the catabolic and anabolic superclusters are deacetylated.

Published
2014
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3. Nature of Pre-Earthquake Phenomena and their Effects on Living Organisms

Author

Friedemann Freund and Viktor Stolc

Subjects
pre-earthquake phenomena, positive holes, ULF (ultralow frequency) waves, ELF (extremely low frequency) waves, air ionization, water oxidation, hydrogen peroxide, physiological effects, Veterinary medicine, SF600-1100, Zoology, QL1-991
Abstract

Earthquakes occur when tectonic stresses build up deep in the Earth before catastrophic rupture. During the build-up of stress, processes that occur in the crustal rocks lead to the activation of highly mobile electronic charge carriers. These charge carriers are able to flow out of the stressed rock volume into surrounding rocks. Such outflow constitutes an electric current, which generates electromagnetic (EM) signals. If the outflow occurs in bursts, it will lead to short EM pulses. If the outflow is continuous, the currents may fluctuate, generating EM emissions over a wide frequency range. Only ultralow and extremely low frequency (ULF/ELF) waves travel through rock and can reach the Earth surface. The outflowing charge carriers are (i) positively charged and (ii) highly oxidizing. When they arrive at the Earth surface from below, they build up microscopic electric fields, strong enough to field-ionize air molecules. As a result, the air above the epicentral region of an impending major earthquake often becomes laden with positive airborne ions. Medical research has long shown that positive airborne ions cause changes in stress hormone levels in animals and humans. In addition to the ULF/ELF emissions, positive airborne ions can cause unusual reactions among animals. When the charge carriers flow into water, they oxidize water to hydrogen peroxide. This, plus oxidation of organic compounds, can cause behavioral changes among aquatic animals.

Published
2013
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4. Adaptation of organisms by resonance of RNA transcription with the cellular redox cycle.

Author

Viktor Stolc, Alena Shmygelska, and Yuri Griko

Subjects
Medicine, Science
Abstract

Sequence variation in organisms differs across the genome and the majority of mutations are caused by oxidation, yet its origin is not fully understood. It has also been shown that the reduction-oxidation reaction cycle is the fundamental biochemical cycle that coordinates the timing of all biochemical processes in the cell, including energy production, DNA replication, and RNA transcription. We show that the temporal resonance of transcriptome biosynthesis with the oscillating binary state of the reduction-oxidation reaction cycle serves as a basis for non-random sequence variation at specific genome-wide coordinates that change faster than by accumulation of chance mutations. This work demonstrates evidence for a universal, persistent and iterative feedback mechanism between the environment and heredity, whereby acquired variation between cell divisions can outweigh inherited variation.

Published
2011
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5. Global identification and characterization of transcriptionally active regions in the rice genome.

Author

Lei Li, Xiangfeng Wang, Rajkumar Sasidharan, Viktor Stolc, Wei Deng, Hang He, Jan Korbel, Xuewei Chen, Waraporn Tongprasit, Pamela Ronald, Runsheng Chen, Mark Gerstein, and Xing Wang Deng

Subjects
Medicine, Science
Abstract

Genome tiling microarray studies have consistently documented rich transcriptional activity beyond the annotated genes. However, systematic characterization and transcriptional profiling of the putative novel transcripts on the genome scale are still lacking. We report here the identification of 25,352 and 27,744 transcriptionally active regions (TARs) not encoded by annotated exons in the rice (Oryza. sativa) subspecies japonica and indica, respectively. The non-exonic TARs account for approximately two thirds of the total TARs detected by tiling arrays and represent transcripts likely conserved between japonica and indica. Transcription of 21,018 (83%) japonica non-exonic TARs was verified through expression profiling in 10 tissue types using a re-array in which annotated genes and TARs were each represented by five independent probes. Subsequent analyses indicate that about 80% of the japonica TARs that were not assigned to annotated exons can be assigned to various putatively functional or structural elements of the rice genome, including splice variants, uncharacterized portions of incompletely annotated genes, antisense transcripts, duplicated gene fragments, and potential non-coding RNAs. These results provide a systematic characterization of non-exonic transcripts in rice and thus expand the current view of the complexity and dynamics of the rice transcriptome.

Published
2007
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6. Private Spaceflight: A New Landscape for Dealing with Medical Risk

Author

Yuri V, Griko, David J, Loftus, Viktor, Stolc, and Elena, Peletskaya

Subjects
Radiation, Ecology, Health, Toxicology and Mutagenesis, Astronauts, Humans, Astronomy and Astrophysics, Space Flight, Agricultural and Biological Sciences (miscellaneous)
Abstract

As NASA and other space agencies make plans to proceed with human exploration missions beyond low earth orbit (LEO), the private sector, including Space X, Virgin Galactic, Blue Origin, Space Adventures and others, echo these plans with initiatives of their own to send humans further into space. Development of more sub-orbital flight opportunities, orbital flight opportunities to LEO and even higher risk endeavors will certainly result in exposure to medical risks for an expanding and heterogeneous population of civilians. To date, a handful of "space tourists" have flown to the International Space Station (ISS), at their own expense, ushering in a new era in which anyone with reasonably good health and even those with physical disability may consider becoming space travelers. Indeed, medical and behavioral issues of healthy, professional astronauts, have not been problematic on short orbital flights. However, recent attempts to test the potential limitations in astronauts on extended duration orbital flights in preparation for future missions beyond LEO raise concern about individual differences in ability to tolerate the hazardous spaceflight environment. Given the rapid development of opportunities for non-professionals and the employees of private companies to travel into space, this is an appropriate time to consider the development of selection strategies for non-government space travelers, including the development of genomic and other modern tools to assess susceptibility to spaceflight risk.

Published
2022
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8. Changes in Human Hair Induced by UV- and Gamma Irradiation

Author

Eugene Galicia, Yuri Griko, Viktor Stolc, David Gomez, and Ervin Palma

Subjects
0301 basic medicine, Fluorophore, Radical, Tryptophan, Gamma ray, General Medicine, Radiation, Fluorescence, Fluorescence spectroscopy, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, chemistry, Biophysics, Steady state (chemistry)
Abstract

The effect of UV- and 137Cs gamma radiation on the structural and chemical integrity of human hair was studied to determine the feasibility of using human hair as a non-invasive biomarker of radiation exposure to ionized gamma- and non-ionized UV-radiation. Steady state tryptophan (Trp) fluorescence and chemical analytical methods were used to evaluate the molecular integrity of Trp fluorophores and SH-groups in hair proteins and to assess the radiation induced damage quantitatively. It was found that human hair fibers were progressively damaged by exposure to both UV- and ionized gamma radiation. Damage to the hair was evidenced by a decrease in the fluorescence intensity as a result of observed depletion of the amino acid tryptophan as well as significant reduction in a number of free SH-groups in hair proteins. Hair damage was dose-dependent for exposures between 0 and 10.0 Gy and 0 - 20 J/cm2 of UV-radiation. Additional results demonstrate that hair-fibers exposed to gamma rays, with much higher quantum energy than UV, undergo a smaller extent of changes in Trp fluorescence than when exposed to lower or equal energy of UV-irradiation. The stable Trp fluorophore appears to be extremely sensitive to UV-radiation in contrast to the ionized gamma radiation whose damage is originated from the reaction of free radicals and direct deposition of energy. We conclude that fluorescence spectroscopy represents a useful tool in the quantitative evaluation of the radiation exposure and could also be used for the rapid and non-invasive assessment of radiation dose i.e. biodosimeter. The approach is simple, non-invasive and appears to have considerable potential that enables quantitative evaluation of radiation dose exposure in a single hair fiber.

Published
2016
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9. Long-Term Study of Heart Rate Variability Responses to Changes in the Solar and Geomagnetic Environment

Author

Alfonsas Vainoras, Minvydas Ragulskis, Viktor Stolc, York Dobyns, Rollin McCraty, Abdullah A. Al-Abdulgader, Michael J. Atkinson, and „Springer' grupė

Subjects
Adult, 010504 meteorology & atmospheric sciences, Heart rate, physiology, analysis, Autonomic nervous system, Solar activity, Electromagnetic fields, adverse effects, Magnetic fields, lcsh:Medicine, 030204 cardiovascular system & hematology, Atmospheric sciences, 01 natural sciences, Article, Magnetics, 03 medical and health sciences, 0302 clinical medicine, Heart Rate, Bayesian multivariate linear regression, Humans, Heart rate variability, Longitudinal Studies, Circadian rhythm, lcsh:Science, Magnetic fields| adverse effects, Heart rate| analysis, 0105 earth and related environmental sciences, Multidisciplinary, lcsh:R, Linear model, 612.172.2 [udc], Middle Aged, Healthy Volunteers, Solar wind, Earth's magnetic field, Linear Models, Heart rate| physiology, Electromagnetic fields| adverse effects, Environmental science, Female, lcsh:Q, Cosmic Radiation
Abstract

This long-term study examined relationships between solar and magnetic factors and the time course and lags of autonomic nervous system (ANS) responses to changes in solar and geomagnetic activity. Heart rate variability (HRV) was recorded for 72 consecutive hours each week over a five-month period in 16 participants in order to examine ANS responses during normal background environmental periods. HRV measures were correlated with solar and geomagnetic variables using multivariate linear regression analysis with Bonferroni corrections for multiple comparisons after removing circadian influences from both datasets. Overall, the study confirms that daily ANS activity responds to changes in geomagnetic and solar activity during periods of normal undisturbed activity and it is initiated at different times after the changes in the various environmental factors and persist over varying time periods. Increase in solar wind intensity was correlated with increases in heart rate, which we interpret as a biological stress response. Increase in cosmic rays, solar radio flux, and Schumann resonance power was all associated with increased HRV and parasympathetic activity. The findings support the hypothesis that energetic environmental phenomena affect psychophysical processes that can affect people in different ways depending on their sensitivity, health status and capacity for self-regulation.

Published
2018
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10. Synchronization of Human Autonomic Nervous System Rhythms with Geomagnetic Activity in Human Subjects

Author

Minvydas Ragulskis, Michael M. Atkinson, Viktor Stolc, Alfonsas Vainoras, Rollin McCraty, Abdullah A. Al-Abdulgader, and MDPI AG (Basel, Switzerland)

Subjects
Adult, Male, heliobiology, geomagnetic field, HRV, Schumann resonance, heart rate variability, solar wind, ANS, autonomic nervous system, cosmic rays, solar radio flux, Cosmic radiation| adverse effects, 010504 meteorology & atmospheric sciences, Health, Toxicology and Mutagenesis, Period (gene), lcsh:Medicine, Heart rate, physiology, Autonomic nervous system, Cosmic radiation, adverse effects, Electromagnetic fields, Magnetic fields, 01 natural sciences, Article, 03 medical and health sciences, 0302 clinical medicine, Rhythm, Heart Rate, Humans, Heart rate variability, Circadian rhythm, Magnetic fields| adverse effects, Aged, 0105 earth and related environmental sciences, Physics, Schumann resonances, Magnetic Phenomena, lcsh:R, Public Health, Environmental and Occupational Health, 612.172.2 [udc], Middle Aged, Geodesy, Circadian Rhythm, Solar wind, Magnetic Fields, Earth's magnetic field, Heart rate| physiology, Electromagnetic fields| adverse effects, Female, 030217 neurology & neurosurgery
Abstract

A coupling between geomagnetic activity and the human nervous system’s function was identified by virtue of continuous monitoring of heart rate variability (HRV) and the time-varying geomagnetic field over a 31-day period in a group of 10 individuals who went about their normal day-to-day lives. A time series correlation analysis identified a response of the group’s autonomic nervous systems to various dynamic changes in the solar, cosmic ray, and ambient magnetic field. Correlation coefficients and p values were calculated between the HRV variables and environmental measures during three distinct time periods of environmental activity. There were significant correlations between the group’s HRV and solar wind speed, Kp, Ap, solar radio flux, cosmic ray counts, Schumann resonance power, and the total variations in the magnetic field. In addition, the time series data were time synchronized and normalized, after which all circadian rhythms were removed. It was found that the participants’ HRV rhythms synchronized across the 31-day period at a period of approximately 2.5 days, even though all participants were in separate locations. Overall, this suggests that daily autonomic nervous system activity not only responds to changes in solar and geomagnetic activity, but is synchronized with the time-varying magnetic fields associated with geomagnetic field-line resonances and Schumann resonances.

Published
2017

11. Time resolved DNA occupancy dynamics during the respiratory oscillation uncover a global reset point in the yeast growth program

Author

Tomoyoshi Soga, Cornelia Amariei, Viktor Stolc, Masaru Tomita, Douglas B. Murray, and Rainer Machné

Subjects
Applied Microbiology, Biochemistry, Genetics and Molecular Biology (miscellaneous), Microbiology, Applied Microbiology and Biotechnology, Transcriptome, chemistry.chemical_compound, Virology, Genetics, Oscillation (cell signaling), Transcriptional regulation, Nucleosome, histone modification, lcsh:QH301-705.5, Molecular Biology, Gene, energetics, respiratory oscillation, biology, anabolism, catabolism, Cell Biology, Chromatin, Cell biology, Histone, lcsh:Biology (General), chemistry, biology.protein, chromatin dynamics, Parasitology, transcription regulation, DNA
Abstract

The structural dynamics of chromatin have been implicated in the regulation of fundamental eukaryotic processes, such as DNA transcription, replication and repair. Although previous studies have revealed that the chromatin landscape, nucleosome remodeling and histone modification events are intimately tied into cellular energetics and redox state, few studies undertake defined time-resolved measurements of these state variables. Here, we use metabolically synchronous, continuously-grown yeast cultures to measure DNA occupancy and track global patterns with respect to the metabolic state of the culture. Combined with transcriptome analyses and ChIP-qPCR experiments, these paint an intriguing picture where genome-wide nucleosome focusing occurs during the recovery of energy charge, followed by clearance of the promoter regions and global transcriptional slow-down, thus indicating a nucleosome-mediated “reset point” for the cycle. The reset begins at the end of the catabolic and stress-response transcriptional programs and ends prior to the start of the anabolic and cell-growth transcriptional program, and the histones on genes from both the catabolic and anabolic superclusters are deacetylated.

Published
2014
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12. ArxA, a new clade of arsenite oxidase within the DMSO reductase family of molybdenum oxidoreductases

Author

Kamrun Zargar, Alison Conrad, Chad W. Saltikov, David L. Bernick, Viktor Stolc, Ronald S. Oremland, Todd M. Lowe, John F. Stolz, and Shelley E. Hoeft

Subjects
DMSO reductase, Oxidase test, Operon, Aroa, Arsenate, Biology, Reductase, biology.organism_classification, Microbiology, chemistry.chemical_compound, Biochemistry, chemistry, Ecology, Evolution, Behavior and Systematics, Bacteria, Arsenite
Abstract

Summary Arsenotrophy, growth coupled to autotrophic arsenite oxidation or arsenate respiratory reduction, occurs only in the prokaryotic domain of life. The enzymes responsible for arsenotrophy belong to distinct clades within the DMSO reductase family of molybdenum-containing oxidoreductases: specifi- cally arsenate respiratory reductase, ArrA, and arsen- ite oxidase, AioA (formerly referred to as AroA and AoxB). A new arsenite oxidase clade, ArxA, repre- sented by the haloalkaliphilic bacterium Alkalilimni- cola ehrlichii strain MLHE-1 was also identified in the photosynthetic purple sulfur bacterium Ectothiorho- dospira sp. strain PHS-1. A draft genome sequence of PHS-1 was completed and an arx operon similar to MLHE-1 was identified. Gene expression studies showed that arxA was strongly induced with arsenite. Microbial ecology investigation led to the identifica- tion of additional arxA-like sequences in Mono Lake and Hot Creek sediments, both arsenic-rich environ- ments in California. Phylogenetic analyses placed these sequences as distinct members of the ArxA clade of arsenite oxidases. ArxA-like sequences were also identified in metagenome sequences of several alkaline microbial mat environments of Yellowstone National Park hot springs. These results suggest that ArxA-type arsenite oxidases appear to be widely dis- tributed in the environment presenting an opportunity for further investigations of the contribution of Arx- dependent arsenotrophy to the arsenic biogeochemi- cal cycle.

Published
2012
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13. NASA Radiation Biomarker WorkshopSeptember 27–28, 2007

Author

Julie A. Leary, Fredric J. Burns, Stephen Franklin, Andrew J. Wyrobek, Nicholas Dainiak, William F. Morgan, Terry C. Pellmar, William F. Blakely, Andrew T M Vaughan, Srinivasan Vijayakumar, Kenneth W. Turteltaub, Viktor Stolc, David J. Loftus, Allen M. Chen, Tore Straume, and Sally A. Amundson

Subjects
Radiation, Individual susceptibility, business.industry, Research community, Biophysics, Biomarker (medicine), Library science, Medicine, Radiology, Nuclear Medicine and imaging, Space radiation, business
Abstract

Straume, T., Amundson, S. A., Blakely, W. F., Burns, F. J., Chen, A., Dainiak, N., Franklin, S., Leary, J. A., Loftus, D. J., Morgan, W. F., Pellmar, T. C., Stolc, V., Turteltaub, K. W., Vaughan, A. T., Vijayakumar, S. and Wyrobek, A. J. NASA Radiation Biomarker Workshop. September 27–28, 2007. Radiat. Res. 170, 393–405 (2008). A summary is provided of presentations and discussions at the NASA Radiation Biomarker Workshop held September 27–28, 2007 at NASA Ames Research Center in Mountain View, CA. Invited speakers were distinguished scientists representing key sectors of the radiation research community. Speakers addressed recent developments in the biomarker and biotechnology fields that may provide new opportunities for health-related assessment of radiation-exposed individuals, including those exposed during long-duration space travel. Topics discussed included the space radiation environment, biomarkers of radiation sensitivity and individual susceptibility, molecular signatures of low-dose ...

Published
2008
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14. High-Resolution Mapping of Epigenetic Modifications of the Rice Genome Uncovers Interplay between DNA Methylation, Histone Methylation, and Gene Expression

Author

Jiming Jiang, Kun He, Songgang Li, Hang He, Xing Wang Deng, Xiangfeng Wang, Weiwei Jin, Xueyong Li, Waraporn Tongprasit, Viktor Stolc, William Terzaghi, Ning Su, and Yeqin Ma

Subjects
Chromatin Immunoprecipitation, Transcription, Genetic, Plant Science, Biology, Methylation, Polymerase Chain Reaction, Epigenesis, Genetic, Euchromatin, Histones, Epigenetics of physical exercise, Gene Expression Regulation, Plant, Histone methylation, Epigenetics, Methylated DNA immunoprecipitation, RNA-Directed DNA Methylation, Research Articles, Epigenomics, Reverse Transcriptase Polymerase Chain Reaction, food and beverages, Oryza, Cell Biology, DNA Methylation, Molecular biology, Differentially methylated regions, DNA methylation, Genome, Plant
Abstract

We present high-resolution maps of DNA methylation and H3K4 di- and trimethylation of two entire chromosomes and two fully sequenced centromeres in rice (Oryza sativa) shoots and cultured cells. This analysis reveals combinatorial interactions between these epigenetic modifications and chromatin structure and gene expression. Cytologically densely stained heterochromatin had less H3K4me2 and H3K4me3 and more methylated DNA than the less densely stained euchromatin, whereas centromeres had a unique epigenetic composition. Most transposable elements had highly methylated DNA but no H3K4 methylation, whereas more than half of protein-coding genes had both methylated DNA and di- and/or trimethylated H3K4. Methylation of DNA but not H3K4 was correlated with suppressed transcription. By contrast, when both DNA and H3K4 were methylated, transcription was only slightly reduced. Transcriptional activity was positively correlated with the ratio of H3K4me3/H3K4me2: genes with predominantly H3K4me3 were actively transcribed, whereas genes with predominantly H3K4me2 were transcribed at moderate levels. More protein-coding genes contained all three modifications, and more transposons contained DNA methylation in shoots than cultured cells. Differential epigenetic modifications correlated to tissue-specific expression between shoots and cultured cells. Collectively, this study provides insights into the rice epigenomes and their effect on gene expression and plant development.

Published
2008
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15. Assessing the performance of different high-density tiling microarray strategies for mapping transcribed regions of the human genome

Author

Mark Gerstein, Ugrappa Nagalakshmi, Jiang Du, Joel Rozowsky, Deyou Zheng, Sherman M. Weissman, Alexander E. Urban, Olof Emanuelsson, Viktor Stolc, Michael Snyder, and Zheng Lian

Subjects
Genetics, Transcription, Genetic, Genome, Human, Chromosomes, Human, Pair 22, Gene Expression Profiling, Quantitative Trait Loci, Chromosome Mapping, Locus (genetics), Replicate, Computational biology, Gene Annotation, Biology, ENCODE, Genome, Cell Line, Gene expression profiling, Methods, Humans, Human genome, DNA microarray, Genetics (clinical), Oligonucleotide Array Sequence Analysis
Abstract

Genomic tiling microarrays have become a popular tool for interrogating the transcriptional activity of large regions of the genome in an unbiased fashion. There are several key parameters associated with each tiling experiment (e.g., experimental protocols and genomic tiling density). Here, we assess the role of these parameters as they are manifest in different tiling-array platforms used for transcription mapping. First, we analyze how a number of published tiling-array experiments agree with established gene annotation on human chromosome 22. We observe that the transcription detected from high-density arrays correlates substantially better with annotation than that from other array types. Next, we analyze the transcription-mapping performance of the two main high-density oligonucleotide array platforms in the ENCODE regions of the human genome. We hybridize identical biological samples and develop several ways of scoring the arrays and segmenting the genome into transcribed and nontranscribed regions, with the aim of making the platforms most comparable to each other. Finally, we develop a platform comparison approach based on agreement with known annotation. Overall, we find that the performance improves with more data points per locus, coupled with statistical scoring approaches that properly take advantage of this, where this larger number of data points arises from higher genomic tiling density and the use of replicate arrays and mismatches. While we do find significant differences in the performance of the two high-density platforms, we also find that they complement each other to some extent. Finally, our experiments reveal a significant amount of novel transcription outside of known genes, and an appreciable sample of this was validated by independent experiments.

Published
2006
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16. Global identification of noncoding RNAs in Saccharomyces cerevisiae by modulating an essential RNA processing pathway

Author

Manoj P. Samanta, Waraporn Tongprasit, Viktor Stolc, Chen-Shan Chin, and Himanshu Sethi

Subjects
Genetics, RNA, Untranslated, Saccharomyces cerevisiae Proteins, Multidisciplinary, Tiling array, Base Sequence, RNase P, Genes, Fungal, Molecular Sequence Data, Saccharomyces cerevisiae, Gene Expression, RNA, Fungal, Biological Sciences, Biology, biology.organism_classification, Genome, Intergenic region, Endoribonucleases, Coding region, RNA, Antisense, RNA Processing, Post-Transcriptional, DNA, Fungal, Gene, Ribonucleoprotein
Abstract

Noncoding RNAs (ncRNAs) perform essential cellular tasks and play key regulatory roles in all organisms. Although several new ncRNAs in yeast were recently discovered by individual studies, to our knowledge no comprehensive empirical search has been conducted. We demonstrate a powerful and versatile method for global identification of previously undescribed ncRNAs by modulating an essential RNA processing pathway through the depletion of a key ribonucleoprotein enzyme component, and monitoring differential transcriptional activities with genome tiling arrays during the time course of the ribonucleoprotein depletion. The entire Saccharomyces cerevisiae genome was scanned during cell growth decay regulated by promoter-mediated depletion of Rpp1 , an essential and functionally conserved protein component of the RNase P enzyme. In addition to most verified genes and ncRNAs, expression was detected in 98 antisense and intergenic regions, 74 that were further confirmed to contain previously undescribed RNAs. A class of ncRNAs, located antisense to coding regions of verified protein-coding genes, is discussed in this article. One member, HRA1 , is likely involved in 18S rRNA maturation.

Published
2006
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17. Identification of transcribed sequences in Arabidopsis thaliana by using high-resolution genome tiling arrays

Author

Clark J. Nelson, John L. Markley, Sebastian Y. Bednarek, David M. Rancour, Himanshu Sethi, Michael R. Sussman, George N. Phillips, Adrian D. Hegeman, Manoj P. Samanta, Craig S. Newman, Waraporn Tongprasit, David C. Nelson, Viktor Stolc, Russell L. Wrobel, Brian G. Fox, Eldon L. Ulrich, Qin Zhao, and Shoudan Liang

Subjects
Proteomics, Optics and Photonics, Spectrometry, Mass, Electrospray Ionization, DNA, Complementary, DNA, Plant, Transcription, Genetic, Arabidopsis, Computational biology, Biology, Photography, RNA, Antisense, RNA, Messenger, Small nucleolar RNA, Gene, Chromatography, High Pressure Liquid, Oligonucleotide Array Sequence Analysis, Genetics, Multidisciplinary, Tiling array, Base Sequence, Arabidopsis Proteins, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide, Gene Expression Profiling, Intron, RNA, Exons, Biological Sciences, Introns, RNA, Plant, Transfer RNA, Genome, Plant, Small nuclear RNA
Abstract

Using a maskless photolithography method, we produced DNA oligonucleotide microarrays with probe sequences tiled throughout the genome of the plant Arabidopsis thaliana . RNA expression was determined for the complete nuclear, mitochondrial, and chloroplast genomes by tiling 5 million 36-mer probes. These probes were hybridized to labeled mRNA isolated from liquid grown T87 cells, an undifferentiated Arabidopsis cell culture line. Transcripts were detected from at least 60% of the nearly 26,330 annotated genes, which included 151 predicted genes that were not identified previously by a similar genome-wide hybridization study on four different cell lines. In comparison with previously published results with 25-mer tiling arrays produced by chromium masking-based photolithography technique, 36-mer oligonucleotide probes were found to be more useful in identifying intron–exon boundaries. Using two-dimensional HPLC tandem mass spectrometry, a small-scale proteomic analysis was performed with the same cells. A large amount of strongly hybridizing RNA was found in regions “antisense” to known genes. Similarity of antisense activities between the 25-mer and 36-mer data sets suggests that it is a reproducible and inherent property of the experiments. Transcription activities were also detected for many of the intergenic regions and the small RNAs, including tRNA, small nuclear RNA, small nucleolar RNA, and microRNA. Expression of tRNAs correlates with genome-wide amino acid usage.

Published
2005
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18. Hybrid MD-Nernst Planck model of α-hemolysin conductance properties

Author

Ioana Cozmuta, James T. O'Keeffe, Deepak Bose, and Viktor Stolc

Subjects
Chemistry, General Chemical Engineering, Analytical chemistry, Ionic bonding, Conductance, Thermodynamics, General Chemistry, Condensed Matter Physics, Open-channel flow, Ion, Molecular dynamics, symbols.namesake, Modeling and Simulation, Electric field, symbols, General Materials Science, Nernst equation, Information Systems, Voltage
Abstract

Motivated by experiments in which an applied electric field translocates polynucleotides through an alpha-hemolysin protein channel causing ionic current transient blockade, a hybrid simulation model is proposed to predict the conductance properties of the open channel. Time scales corresponding to ion permeation processes are reached using the Poisson-Nemst-Planck (PNP) electro-diffusion model in which both solvent and local ion concentrations are represented as a continuum. The diffusion coefficients of the ions (K(+) and Cl(-)) input in the PNP model are, however, calculated from all-atom molecular dynamics (MD). In the MD simulations, a reduced representation of the channel is used. The channel is solvated in a 1 M KCI solution, and an external electric field is applied. The pore specific diffusion coefficients for both ionic species are reduced 5-7 times in comparison to bulk values. Significant statistical variations (17-45%) of the pore-ions diffusivities are observed. Within the statistics, the ionic diffusivities remain invariable for a range of external applied voltages between 30 and 240mV. In the 2D-PNP calculations, the pore stem is approximated by a smooth cylinder of radius approx. 9A with two constriction blocks where the radius is reduced to approx. 6A. The electrostatic potential includes the contribution from the atomistic charges. The MD-PNP model shows that the atomic charges are responsible for the rectifying behaviour and for the slight anion selectivity of the a-hemolysin pore. Independent of the hierarchy between the anion and cation diffusivities, the anionic contribution to the total ionic current will dominate. The predictions of the MD-PNP model are in good agreement with experimental data and give confidence in the present approach of bridging time scales by combining a microscopic and macroscopic model.

Published
2005
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19. The ENCODE (ENCyclopedia Of DNA Elements) Project

Author

Jonathan H. Dennis, Michael Brudno, Anindya Dutta, Richard M. Myers, Ian Dunham, Eduardo Eyras, S. S. Marticke, Alexandre Reymond, Anason S. Halees, Greg Schuler, M. G. Rosenfeld, Mikhail Nefedov, Robert E. Kingston, Elizabeth Anton, Tyra G. Wolfsberg, Alice C. Young, Kris A. Wetterstrand, C. K. Glass, Nancy F. Hansen, Gayle K. Clelland, Diane I. Schroeder, Jean L. Chang, H. Shin, Zhou Zhu, Nigel P. Carter, William Stafford Noble, Jenny McDowell, Ugrappa Nagalakshmi, Heike Fiegler, Philipp Kapranov, Peggy J. Farnham, Joanna C. Fowler, S. C. Harvey, Michael O. Dorschner, D. R. Inman, George V. Popescu, Jan-Jaap Wesselink, P. Groth, Baoli Zhu, H. Hirsch, James C. Wallace, Elise A. Feingold, S. Jin, Gabriel Robins, Thomas R. Gingeras, F. Denoeud, W. Tongprasit, Robert Castelo, Ross C. Hardison, John A. Stamatoyannopoulos, Joel Rozowsky, Eric A. Stone, Zheng Lian, J. E. Norton, Y. S. Kwon, Viktor Stolc, Michael C. Pirrung, Min-Feng Yu, A. Yang, W. J. Kent, Peter J. Sabo, Stephen Hartman, Stylianos E. Antonarakis, Tae Hoon Kim, H. Kim, Baishali Maskeri, Thomas Royce, R. Luna, Sherman M. Weissman, Tim Hubbard, Oliver M. Dovey, Ewan Birney, Kate R. Rosenbloom, Robert M. Andrews, Damian Keefe, Arend Sidow, D. Zhou, Jane Grimwood, Ulas Karaoz, Zhiping Weng, H. Burden, Michael C. Zody, Hiram Clawson, Gerry Bouffard, S. van Calcar, Mark Dickson, Kevin Struhl, Ingeborg Holt, Emmanouil T. Dermitzakis, T. J. Vasicek, Peter J. Good, Charles R. Cantor, Hari Tammana, Josée Dostie, Prachi Shah, Elliott H. Margulies, Peter D. Ellis, Mark S. Guyer, Christopher M. Taylor, Patrick A. Navas, Dione Kampa, Colin N. Dewey, Lior Pachter, Christof Koch, George Asimenos, James R R Whittle, Gregory E. Crawford, Jane B. Lian, Pamela J. Thomas, Kazutoyo Osoegawa, Webb Miller, Chunxu Qu, Nele Gheldof, Keith D. James, Sandeep Patel, Todd Richmond, Jacquelyn R. Idol, Michael A. Singer, Tomoko M. Tabuchi, Adam Siepel, Yutao Fu, David Vetrie, Long H. Nguyen, Michael Snyder, William H. Majoros, Michael R. Brent, Nathan D. Trinklein, Leah O. Barrera, Mark Gerstein, Srinka Ghosh, Sara J. Hartman, Jade P. Vinson, C. L. Middle, Sambath Chung, George Stamatoyannopoulos, Y. Nakayama, George M. Church, Job Dekker, Olof Emanuelsson, Julien Lagarde, Roderic Guigó, Marco A. Marra, Jeremy Schmutz, Daryl J. Thomas, Yong Yu, M. R. McCormick, Xiang-Dong Fu, Richard Humbert, Jennifer L. Ashurst, Alexander E. Urban, Sarah Wilcox, Ghia Euskirchen, Michael Kamal, Cordelia Langford, Jacquie Schein, Gregory M. Cooper, Paul Bertone, Eric S. Lander, C. Ding, Antonio Piccolboni, Steven L. Salzberg, Rhonda Harrison, Matthew J. Oberley, E. A. Sekinger, Mihaela Pertea, Bing Ren, H. K. Kim, Roland Green, Shelley Force Aldred, Laura Elnitski, Michael Hawrylycz, Andrew J. Mungall, Kerstin Lindblad-Toh, David B. Jaffe, Andreas D. Baxevanis, L. Liefer, Michele Clamp, David Haussler, Jill Cheng, John L. Rinn, S. Kamholz, Vicki L. Wraight, H. Sethi, Francis S. Collins, Steven J.M. Jones, Serafim Batzoglou, P. J. De Jong, Matthew E. Portnoy, Stefan Bekiranov, M. McArthur, Shu-Jin Luo, Eric D. Green, Robert W. Blakesley, Tarjei S. Mikkelsen, Z. Ye, Pawandeep Dhami, and Neerja Karnani

Subjects
Pilot phase, Pilot Projects, Computational biology, Regulatory Sequences, Nucleic Acid, Biology, ENCODE, Access to Information, Evolution, Molecular, Annotation, chemistry.chemical_compound, Animals, Humans, International HapMap Project, Conserved Sequence, Publishing, Genetics, Internet, Multidisciplinary, Genome, Human, Information Dissemination, GENCODE, Computational Biology, Proteins, Genomics, Sequence Analysis, DNA, United States, National Institutes of Health (U.S.), chemistry, Encyclopedia, Human genome, Databases, Nucleic Acid, DNA
Abstract

The ENCyclopedia Of DNA Elements (ENCODE) Project aims to identify all functional elements in the human genome sequence. The pilot phase of the Project is focused on a specified 30 megabases (∼1%) of the human genome sequence and is organized as an international consortium of computational and laboratory-based scientists working to develop and apply high-throughput approaches for detecting all sequence elements that confer biological function. The results of this pilot phase will guide future efforts to analyze the entire human genome.

Published
2004
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20. Characterization of synthetic DNA bar codes in Saccharomyces cerevisiae gene-deletion strains

Author

Olufisayo Jejelowo, Robert G. Eason, Zelek S. Herman, Ronald W. Davis, Nader Pourmand, Waraporn Tongprasit, Kevin Anthony, and Viktor Stolc

Subjects
Genetics, Mutation, Multidisciplinary, biology, Oligonucleotide, Genes, Fungal, Saccharomyces cerevisiae, Nucleic Acid Hybridization, Biological Sciences, biology.organism_classification, medicine.disease_cause, Polymerase Chain Reaction, Yeast, law.invention, Nucleic acid thermodynamics, law, medicine, Pyrosequencing, DNA, Fungal, Gene, Gene Deletion, Polymerase chain reaction, DNA Primers
Abstract

Incorporation of strain-specific synthetic DNA tags into yeast Saccharomyces cerevisiae gene-deletion strains has enabled identification of gene functions by massively parallel growth rate analysis. However, it is important to confirm the sequences of these tags, because mutations introduced during construction could lead to significant errors in hybridization performance. To validate this experimental system, we sequenced 11,812 synthetic 20-mer molecular bar codes and adjacent sequences (>1.8 megabases synthetic DNA) by pyrosequencing and Sanger methods. At least 31% of the genome-integrated 20-mer tags contain differences from those originally synthesized. However, these mutations result in anomalous hybridization in only a small subset of strains, and the sequence information enables redesign of hybridization probes for arrays. The robust performance of the yeast gene-deletion dual oligonucleotide bar-code design in array hybridization validates the use of molecular bar codes in living cells for tracking their growth phenotype.

Published
2004
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21. Rpp2, an essential protein subunit of nuclear RNase P, is required for processing of precursor tRNAs and 35S precursor rRNA in Saccharomyces cerevisiae

Author

Sidney Altman, Viktor Stolc, and Alexander Katz

Subjects
Mitochondrial RNA processing, Multidisciplinary, Nuclear RNase P, RNase P, Protein subunit, Genes, Fungal, Molecular Sequence Data, RNA, Fungal, Saccharomyces cerevisiae, Biological Sciences, Biology, Ribosomal RNA, Molecular biology, RNase PH, Ribonuclease P, RNase MRP, RNA, Transfer, Biochemistry, Endoribonucleases, Transfer RNA, RNA Precursors, Humans, RNA, Catalytic, Sequence Deletion
Abstract

RPP2 , an essential gene that encodes a 15.8-kDa protein subunit of nuclear RNase P, has been identified in the genome of Saccharomyces cerevisiae . Rpp2 was detected by sequence similarity with a human protein, Rpp20, which copurifies with human RNase P. Epitope-tagged Rpp2 can be found in association with both RNase P and RNase mitochondrial RNA processing in immunoprecipitates from crude extracts of cells. Depletion of Rpp2 protein in vivo causes accumulation of precursor tRNAs with unprocessed introns and 5′ and 3′ termini, and leads to defects in the processing of the 35S precursor rRNA. Rpp2-depleted cells are defective in processing of the 5.8S rRNA. Rpp2 immunoprecipitates cleave both yeast precursor tRNAs and precursor rRNAs accurately at the expected sites and contain the Rpp1 protein orthologue of the human scleroderma autoimmune antigen, Rpp30. These results demonstrate that Rpp2 is a protein subunit of nuclear RNase P that is functionally conserved in eukaryotes from yeast to humans.

Published
1998
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22. Rpp1, an essential protein subunit of nuclear RNase P required for processing of precursor tRNA and 35S precursor rRNA inSaccharomyces cerevisiae

Author

Viktor Stolc and Sidney Altman

Subjects
Saccharomyces cerevisiae Proteins, Macromolecular Substances, RNase P, Genes, Fungal, Molecular Sequence Data, Endoribonuclease, Saccharomyces cerevisiae, Biology, Autoantigens, RNase PH, Ribonuclease P, RNA, Transfer, Endoribonucleases, RNA Precursors, Genetics, Humans, RNA, Catalytic, Amino Acid Sequence, Cloning, Molecular, RRNA processing, Base Sequence, Sequence Homology, Amino Acid, Nuclear RNase P, RNA, RNA, Fungal, Molecular biology, RNase MRP, RNA, Ribosomal, Transfer RNA, Sequence Alignment, Research Paper, Developmental Biology
Abstract

The gene for an essential protein subunit of nuclear RNase P fromSaccharomyces cerevisiae has been cloned. The gene for this protein, RPP1, was identified by virtue of its homology with a human scleroderma autoimmune antigen, Rpp30, which copurifies with human RNase P. Epitope-tagged Rpp1 can be found in association with both RNase P RNA and a related endoribonuclease, RNase MRP RNA, in immunoprecipitates from crude extracts of cells. Depletion of Rpp1 in vivo leads to the accumulation of precursor tRNAs with unprocessed 5′ and 3′ termini and reveals rRNA processing defects that have not been described previously for proteins associated with RNase P or RNase MRP. Immunoprecipitated complexes cleave both yeast precursor tRNAs and precursor rRNAs.

Published
1997
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24. Genome-wide direct target analysis reveals a role for SHORT-ROOT in root vascular patterning through cytokinin homeostasis

Author

Viktor Stolc, Xing Wang Deng, Mikiko Kojima, Mikhail Kovtun, Hitoshi Sakakibara, Hongchang Cui, and Yueling Hao

Subjects
Chromatin Immunoprecipitation, Cytokinins, Physiology, Green Fluorescent Proteins, Arabidopsis, Plant Science, Phloem, chemistry.chemical_compound, Gene Expression Regulation, Plant, Genetics, Cluster Analysis, Homeostasis, cardiovascular diseases, Lateral root formation, Transcription factor, Body Patterning, Oligonucleotide Array Sequence Analysis, Regulation of gene expression, Microscopy, Confocal, biology, Arabidopsis Proteins, fungi, Development and Hormone Action, food and beverages, Meristem, biology.organism_classification, Molecular biology, Cell biology, Pericycle, Phenotype, chemistry, Stele, Cytokinin, Mutation, cardiovascular system, Plant Vascular Bundle, Genome, Plant, circulatory and respiratory physiology, Transcription Factors
Abstract

SHORT-ROOT (SHR) is a key regulator of root growth and development in Arabidopsis (Arabidopsis thaliana). Made in the stele, the SHR protein moves into an adjacent cell layer, where it specifies endodermal cell fate; it is also essential for apical meristem maintenance, ground tissue patterning, vascular differentiation, and lateral root formation. Much has been learned about the mechanism by which SHR controls radial patterning, but how it regulates other aspects of root morphogenesis is still unclear. To dissect the SHR developmental pathway, we have determined the genome-wide locations of SHR direct targets using a chromatin immunoprecipitation followed by microarray analysis method. K-means clustering analysis not only identified additional quiescent center-specific SHR targets but also revealed a direct role for SHR in gene regulation in the pericycle and xylem. Using cell type-specific markers, we showed that in shr, the phloem and the phloem-associated pericycle expanded, whereas the xylem and xylem-associated pericycle diminished. Interestingly, we found that cytokinin level was elevated in shr and that exogenous cytokinin conferred a shr-like vascular patterning phenotype in wild-type root. By chromatin immunoprecipitation-polymerase chain reaction and reverse transcription-polymerase chain reaction assays, we showed that SHR regulates cytokinin homeostasis by directly controlling the transcription of cytokinin oxidase 3, a cytokinin catabolism enzyme preferentially expressed in the stele. Finally, overexpression of a cytokinin oxidase in shr alleviated its vascular patterning defect. On the basis of these results, we suggest that one mechanism by which SHR controls vascular patterning is the regulation of cytokinin homeostasis.

Published
2011

25. Polymorphism of Cyclic 3´,5´-Adenosine Monophosphate Stimulation in Rat Erythrocytes

Author

Viktor Stolc

Subjects
Male, Adenosine monophosphate, medicine.medical_specialty, Erythrocytes, Stimulation, Biology, chemistry.chemical_compound, Species Specificity, 1-Methyl-3-isobutylxanthine, Rats, Inbred BN, Internal medicine, Cyclic AMP, medicine, Animals, Polymorphism, Genetic, Isoproterenol, Rats, Inbred Strains, Hematology, General Medicine, Propranolol, Rats, Rats, Inbred ACI, Red blood cell, medicine.anatomical_structure, Endocrinology, chemistry, Rats, Inbred Lew, Female, Adenylyl Cyclases
Abstract

Significant differences were found in the cyclic 3',5'-adenosine monophosphate (cAMP) levels in (-)-isoproterenol-stimulated rat erythrocytes. The BN strain had the highest level (13.1 +/- 1.29 pmol cAMP/10 mg Hb) and the LEW strain had the lowest cAMP level (3.29 +/- 1.76 pmol cAMP/10 mg Hb) in the erythrocytes. The high levels were inherited in three intercrosses in a dominant fashion. The results of the backcross breeding suggested diallelic inheritance. However, the polygenic effect was not ruled out.

Published
1991
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26. Meeting Report--NASA Radiation Biomarker Workshop

Author

Allen M. Chen, William F. Blakely, David J. Loftus, Srinivasan Vijayakumar, William F. Morgan, Stephen Franklin, Kenneth W. Turteltaub, Tore Straume, Terry C. Pellmar, Andrew J. Wyrobek, Frederic J. Burns, Andrew T M Vaughan, Julie A. Leary, Sally A. Amundson, Viktor Stolc, and Nicholas Dainiak

Subjects
Summary conclusions, Biodefense, medicine.medical_specialty, Individual susceptibility, business.industry, Nanotechnology, Space radiation, Biodosimetry, Radiation oncology, Medicine, Biomarker (medicine), Medical physics, business, Cancer risk
Abstract

A summary is provided of presentations and discussions from the NASA Radiation Biomarker Workshop held September 27-28, 2007, at NASA Ames Research Center in Mountain View, California. Invited speakers were distinguished scientists representing key sectors of the radiation research community. Speakers addressed recent developments in the biomarker and biotechnology fields that may provide new opportunities for health-related assessment of radiation-exposed individuals, including for long-duration space travel. Topics discussed include the space radiation environment, biomarkers of radiation sensitivity and individual susceptibility, molecular signatures of low-dose responses, multivariate analysis of gene expression, biomarkers in biodefense, biomarkers in radiation oncology, biomarkers and triage following large-scale radiological incidents, integrated and multiple biomarker approaches, advances in whole-genome tiling arrays, advances in mass-spectrometry proteomics, radiation biodosimetry for estimation of cancer risk in a rat skin model, and confounding factors. Summary conclusions are provided at the end of the report.

Published
2008
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27. LINKAGE OF NEUTROPHIL RESPONSE TO A MUTAGEN GENE (Nrm-1) TO THE AGOUTI LOCUS IN THE RAT

Author

Viktor Stolc

Subjects
Male, Genetic Linkage, Neutrophils, Offspring, Neutrophile, Immunology, Locus (genetics), Immunogenetics, Biology, Leukocyte Count, Species Specificity, Gene mapping, hemic and lymphatic diseases, Genetics, Animals, Allele, Gene, Alleles, Crosses, Genetic, Methylnitrosourea, Phenotype, Molecular biology, Rats, Genes, Female, Mutagens
Abstract

SUMMARY The ACI or BDIV rats responded with decreased or increased neutrophil levels in blood after the N-methyl-N-nitrosourea (MNU) administration. The F1 hybrids had decreased neutrophil counts, and the BDIV × (BDIV × AC1)Fl backcross offspring showed two phenotypes. The sex of the rats and the neutrophil response to MNU assorted independently. The results indicated that the neutrophil response to MNU was regulated by autosomal gene Nrm-1 with two alleles. The Nrm-Id regulates the decrease and the Nrm-1i regulates the increase of neutrophils in blood after the MNU administration. The results were confirmed by the SKUMIX computer program. We found that the Nrm-1 gene was linked to the agouti locus (chi-square = 10–3, P < 0.001). The map distance between two genes was 33 ± 5 cM. The Nrm-1 gene thus resides on the linkage group IV of the rat.

Published
1990
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28. In-depth query of large genomes using tiling arrays

Author

Manoj Pratim, Samanta, Waraporn, Tongprasit, and Viktor, Stolc

Subjects
Genome, Transcription, Genetic, Genome, Human, Animals, Computational Biology, Humans, Nucleic Acid Hybridization, DNA, Intergenic, DNA Probes, Molecular Biology, Oligonucleotide Array Sequence Analysis
Abstract

Identification of the transcribed regions in the newly sequenced genomes is one of the major challenges of postgenomic biology. Among different alternatives for empirical transcriptome mapping, whole-genome tiling array experiment emerged as the most comprehensive and unbiased approach. This relatively new method uses high-density oligonucleotide arrays with probes chosen uniformly from both strands of the entire genomes including all genic and intergenic regions. By hybridizing the arrays with tissue specific or pooled RNA samples, a genome-wide picture of transcription can be derived. This chapter discusses computational tools and techniques necessary to successfully conduct genome tiling array experiments.

Published
2007

29. In-Depth Query of Large Genomes Using Tiling Arrays

Author

Manoj P. Samanta, Waraporn Tongprasit, and Viktor Stolc

Subjects
Intergenic region, Tiling array, Computer science, Tissue specific, Computational biology, Oligonucleotide Arrays, Genome
Abstract

Identification of the transcribed regions in the newly sequenced genomes is one of the major challenges of postgenomic biology. Among different alternatives for empirical transcriptome mapping, whole-genome tiling array experiment emerged as the most comprehensive and unbiased approach. This relatively new method uses high-density oligonucleotide arrays with probes chosen uniformly from both strands of the entire genomes including all genic and intergenic regions. By hybridizing the arrays with tissue specific or pooled RNA samples, a genome-wide picture of transcription can be derived. This chapter discusses computational tools and techniques necessary to successfully conduct genome tiling array experiments.

Published
2007
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30. Analysis of oligo hybridization properties by high-resolution tiling microarrays in rice

Author

Xiangfeng Wang, Jun Wang, Waraporn Tongprasit, Viktor Stolc, Lei Li, Xing Wang Deng, Chen Chen, and Songgang Li

Subjects
In situ, Genetics, Oligonucleotide, Microarray analysis techniques, Complementary DNA, Computational biology, DNA microarray, Oligonucleotide synthesis, Biology, DNA sequencing, GC-content
Abstract

Rice genome sequencing and computational annotation provide a static map for understanding this model of Gramineae species. With the development of in situ oligonucleotide synthesis technology, tiling-path microarrays have become a dynamic and efficient way for monitoring large-scale transcriptional activities and detecting novel transcribed elements missed by software. Unlike conventional cDNA or oligonucleotide arrays, tiling-path platforms employ the full extent of oligos covering given genomic regions, and thus offer excellent experimental conditions in which to assay the properties of oligos in terms of their specificity and efficiency of hybridization to their corresponding targets. Here, we report a tiling-path microarray analysis of a 1-Mb region (10 to 11 Mb) in japonica rice chromosome 10, which was tiled by a 36-mer oligo set at a resolution of 5 bp. Our analysis focused on three major factors of oligo hybridization properties, including GC content, melting temperature (Tm), and the repetitiveness of oligo sequences.

Published
2007
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31. Mapping of transcription factor binding regions in mammalian cells by ChIP: Comparison of array- and sequencing-based technologies

Author

Zhengdong D. Zhang, Michael Snyder, Wah Heng Lee, Sherman M. Weissman, Chia-Lin Wei, Olof Emanuelsson, Joel Rozowsky, Ghia Euskirchen, Stephen Hartman, Yijun Ruan, Viktor Stolc, and Mark Gerstein

Subjects
Chromatin Immunoprecipitation, Computational biology, Biology, ENCODE, DNA sequencing, chemistry.chemical_compound, DNA Microarray Analysis, Genetics, Hardware_INTEGRATEDCIRCUITS, Methods, Animals, Humans, Genetics (clinical), Oligonucleotide Array Sequence Analysis, Tiling array, Hardware_MEMORYSTRUCTURES, Binding Sites, Oligonucleotide, Genome, Human, Sequence Analysis, DNA, Microfluidic Analytical Techniques, STAT1 Transcription Factor, chemistry, Human genome, Chromatin immunoprecipitation, DNA, HeLa Cells
Abstract

Recent progress in mapping transcription factor (TF) binding regions can largely be credited to chromatin immunoprecipitation (ChIP) technologies. We compared strategies for mapping TF binding regions in mammalian cells using two different ChIP schemes: ChIP with DNA microarray analysis (ChIP-chip) and ChIP with DNA sequencing (ChIP-PET). We first investigated parameters central to obtaining robust ChIP-chip data sets by analyzing STAT1 targets in the ENCODE regions of the human genome, and then compared ChIP-chip to ChIP-PET. We devised methods for scoring and comparing results among various tiling arrays and examined parameters such as DNA microarray format, oligonucleotide length, hybridization conditions, and the use of competitor Cot-1 DNA. The best performance was achieved with high-density oligonucleotide arrays, oligonucleotides ≥50 bases (b), the presence of competitor Cot-1 DNA and hybridizations conducted in microfluidics stations. When target identification was evaluated as a function of array number, 80%–86% of targets were identified with three or more arrays. Comparison of ChIP-chip with ChIP-PET revealed strong agreement for the highest ranked targets with less overlap for the low ranked targets. With advantages and disadvantages unique to each approach, we found that ChIP-chip and ChIP-PET are frequently complementary in their relative abilities to detect STAT1 targets for the lower ranked targets; each method detected validated targets that were missed by the other method. The most comprehensive list of STAT1 binding regions is obtained by merging results from ChIP-chip and ChIP-sequencing. Overall, this study provides information for robust identification, scoring, and validation of TF targets using ChIP-based technologies.

Published
2007

32. Analysis of transcription factor HY5 genomic binding sites revealed its hierarchical role in light regulation of development

Author

Xing Wang Deng, Jungeun Lee, Pablo Figueroa, Hongyu Zhao, Kun He, Waraporn Tongprasit, Ilha Lee, Viktor Stolc, Horim Lee, and Ying Gao

Subjects
Chromatin Immunoprecipitation, Light, Arabidopsis, Plant Science, Biology, Genes, Plant, Epitopes, Gene Expression Regulation, Plant, Binding site, Photosynthesis, Promoter Regions, Genetic, Gene, Transcription factor, Research Articles, Genetics, Binding Sites, Arabidopsis Proteins, Gene Expression Profiling, Nuclear Proteins, Promoter, Cell Biology, Plants, Genetically Modified, Circadian Rhythm, DNA binding site, Gene expression profiling, Basic-Leucine Zipper Transcription Factors, Organ Specificity, Transcription Factor Gene, Chromatin immunoprecipitation, Acyltransferases, Genome, Plant, Protein Binding
Abstract

The transcription factor LONG HYPOCOTYL5 (HY5) acts downstream of multiple families of the photoreceptors and promotes photomorphogenesis. Although it is well accepted that HY5 acts to regulate target gene expression, in vivo binding of HY5 to any of its target gene promoters has yet to be demonstrated. Here, we used a chromatin immunoprecipitation procedure to verify suspected in vivo HY5 binding sites. We demonstrated that in vivo association of HY5 with promoter targets is not altered under distinct light qualities or during light-to-dark transition. Coupled with DNA chip hybridization using a high-density 60-nucleotide oligomer microarray that contains one probe for every 500 nucleotides over the entire Arabidopsis thaliana genome, we mapped genome-wide in vivo HY5 binding sites. This analysis showed that HY5 binds preferentially to promoter regions in vivo and revealed >3000 chromosomal sites as putative HY5 binding targets. HY5 binding targets tend to be enriched in the early light-responsive genes and transcription factor genes. Our data thus support a model in which HY5 is a high hierarchical regulator of the transcriptional cascades for photomorphogenesis.

Published
2007

33. Identification of an in vitro transcription-based artifact affecting oligonucleotide microarrays

Author

David C. Nelson, Michael R. Sussman, Matthew J. Rodesch, Manoj P. Samanta, Viktor Stolc, and Dana J. Wohlbach

Subjects
Transcription, Genetic, Microarrays, Biophysics, Expression, Biology, Biochemistry, Genome, Chips, chemistry.chemical_compound, Structural Biology, Genetics, Molecular Biology, Gene, Oligonucleotide Array Sequence Analysis, Artifact (error), Tiling array, Base Sequence, Nucleotides, DNA, Cell Biology, Genes, chemistry, RNA, DNA microarray, Primer (molecular biology), Sequence motif, Artifacts
Abstract

This study identified the widely used T7 in vitro transcription system as a major source of artifact in the tiling array data from nine eukaryotic genomes. The most affected probes contained a sequence motif complementary to the +1 to +9 initial transcribed sequence (ITS) of the T7-(dT)24 primer. The abundance of 5′ ITS cRNA fragments produced during target preparation was sufficient to drive undesirable hybridization. A new T7-(dT)24 primer with a modified ITS was designed that shifts the artifactual motifs as predicted and reduces the effect of the artifact. A computational algorithm was generated to filter out the likely artifactual probes from existing whole-genome tiling array data and improve probe selection. Further studies of Arabidopsis thaliana were conducted using both T7-(dT)24 primers. While the artifact affected transcript discovery with tiling arrays, it showed only a minor impact on measurements of gene expression using commercially available ‘gene-only’ expression arrays.

Published
2007

34. A core transcriptional network for early mesoderm development in Drosophila melanogaster

Author

Waraporn Tongprasit, Marc Brehme, Viktor Stolc, Charles Girardot, Thomas Sandmann, and Eileen E. M. Furlong

Subjects
Mef2, Mesoderm, Chromatin Immunoprecipitation, animal structures, Embryonic Development, Genetics, medicine, Animals, Drosophila Proteins, Gene Regulatory Networks, Gene, Transcription factor, biology, Microarray analysis techniques, Twist-Related Protein 1, Gene Expression Regulation, Developmental, ChIP-on-chip, biology.organism_classification, Cell biology, medicine.anatomical_structure, Drosophila melanogaster, Enhancer Elements, Genetic, embryonic structures, Chromatin immunoprecipitation, Developmental Biology, Research Paper
Abstract

Embryogenesis is controlled by large gene-regulatory networks, which generate spatially and temporally refined patterns of gene expression. Here, we report the characteristics of the regulatory network orchestrating early mesodermal development in the fruitfly Drosophila, where the transcription factor Twist is both necessary and sufficient to drive development. Through the integration of chromatin immunoprecipitation followed by microarray analysis (ChIP-on-chip) experiments during discrete time periods with computational approaches, we identified >2000 Twist-bound cis-regulatory modules (CRMs) and almost 500 direct target genes. Unexpectedly, Twist regulates an almost complete cassette of genes required for cell proliferation in addition to genes essential for morophogenesis and cell migration. Twist targets almost 25% of all annotated Drosophila transcription factors, which may represent the entire set of regulators necessary for the early development of this system. By combining in vivo binding data from Twist, Mef2, Tinman, and Dorsal we have constructed an initial transcriptional network of early mesoderm development. The network topology reveals extensive combinatorial binding, feed-forward regulation, and complex logical outputs as prevalent features. In addition to binary activation and repression, we suggest that Twist binds to almost all mesodermal CRMs to provide the competence to integrate inputs from more specialized transcription factors.

Published
2007

35. Global identification and characterization of transcriptionally active regions in the rice genome

Author

Runsheng Chen, Lei Li, Wei Deng, Jan O. Korbel, Xuewei Chen, Xiangfeng Wang, Hang He, Rajkumar Sasidharan, Mark Gerstein, Waraporn Tongprasit, Viktor Stolc, Pamela C. Ronald, and Xing Wang Deng

Subjects
Transcriptional Activation, 0106 biological sciences, DNA, Complementary, DNA, Plant, Transcription, Genetic, lcsh:Medicine, Biology, Genes, Plant, 01 natural sciences, Genome, Genetics and Genomics/Plant Genetics and Gene Expression, DNA, Antisense, Conserved sequence, Transcriptome, 03 medical and health sciences, Genetics and Genomics/Genomics, lcsh:Science, Gene, Conserved Sequence, 030304 developmental biology, Genetics, 0303 health sciences, Multidisciplinary, Tiling array, Oryza sativa, Genetics and Genomics/Functional Genomics, Gene Expression Profiling, lcsh:R, Life Sciences, food and beverages, Genetics and Genomics, Genetics and Genomics/Gene Expression, Oryza, Exons, Genome project, Genetics and Genomics/Bioinformatics, Gene expression profiling, RNA, Plant, Nucleic Acid Conformation, Genetics and Genomics/Gene Discovery, lcsh:Q, Genome, Plant, Research Article, 010606 plant biology & botany
Abstract

Genome tiling microarray studies have consistently documented rich transcriptional activity beyond the annotated genes. However, systematic characterization and transcriptional profiling of the putative novel transcripts on the genome scale are still lacking. We report here the identification of 25,352 and 27,744 transcriptionally active regions (TARs) not encoded by annotated exons in the rice (Oryza. sativa) subspecies japonica and indica, respectively. The non-exonic TARs account for approximately two thirds of the total TARs detected by tiling arrays and represent transcripts likely conserved between japonica and indica. Transcription of 21,018 (83%) japonica non-exonic TARs was verified through expression profiling in 10 tissue types using a re-array in which annotated genes and TARs were each represented by five independent probes. Subsequent analyses indicate that about 80% of the japonica TARs that were not assigned to annotated exons can be assigned to various putatively functional or structural elements of the rice genome, including splice variants, uncharacterized portions of incompletely annotated genes, antisense transcripts, duplicated gene fragments, and potential non-coding RNAs. These results provide a systematic characterization of non-exonic transcripts in rice and thus expand the current view of the complexity and dynamics of the rice transcriptome.

Published
2007

36. The Transcriptome of the Sea Urchin Embryo

Author

R. Andrew Cameron, Eric H. Davidson, Manoj P. Samanta, Waraporn Tongprasit, Viktor Stolc, Sorin Istrail, and Qiang Tu

Subjects
Embryo, Nonmammalian, RNA, Untranslated, Transcription, Genetic, ved/biology.organism_classification_rank.species, Embryonic Development, Molecular Probe Techniques, Biology, Genome, Transcriptome, Intergenic region, Animals, RNA, Messenger, Model organism, Strongylocentrotus purpuratus, Gene, Oligonucleotide Array Sequence Analysis, Genetics, Multidisciplinary, Tiling array, ved/biology, Gene Expression Profiling, Intracellular Signaling Peptides and Proteins, Computational Biology, Gene Expression Regulation, Developmental, Nucleic Acid Hybridization, Gastrula, Genome project, Blastula, biology.organism_classification, embryonic structures, Signal Transduction, Transcription Factors
Abstract

The sea urchin Strongylocentrotus purpuratus is a model organism for study of the genomic control circuitry underlying embryonic development. We examined the complete repertoire of genes expressed in the S. purpuratus embryo, up to late gastrula stage, by means of high-resolution custom tiling arrays covering the whole genome. We detected complete spliced structures even for genes known to be expressed at low levels in only a few cells. At least 11,000 to 12,000 genes are used in embryogenesis. These include most of the genes encoding transcription factors and signaling proteins, as well as some classes of general cytoskeletal and metabolic proteins, but only a minor fraction of genes encoding immune functions and sensory receptors. Thousands of small asymmetric transcripts of unknown function were also detected in intergenic regions throughout the genome. The tiling array data were used to correct and authenticate several thousand gene models during the genome annotation process.

Published
2006

37. The Genome of the Sea Urchin Strongylocentrotus purpuratus

Author

Amro Hamdoun, Virginia Brockton, Huyen Dinh, Qiang Tu, Richard O. Hynes, Maria Ina Arnone, Wratko Hlavina, L. Courtney Smith, Mariano A. Loza, David R. Burgess, Matthew P. Hoffman, Florian Raible, Qiu Autumn Yuan, Geoffrey Okwuonu, Mark Y. Tong, Jennifer Hume, Donna Maglott, Manisha Goel, Olivier Fedrigo, Manuel L. Gonzalez-Garay, Celina E. Juliano, Judith Hernandez, Gary M. Wessel, William F. Marzluff, Audrey J. Majeske, Christian Gache, Louise Duloquin, Xingzhi Song, François Lapraz, Fowler J, Alexandre Souvorov, Jared V. Goldstone, Georgia Panopoulou, Sandra Hines, Kyle M. Judkins, Clay Davis, Christine G. Elsik, Paul Kitts, Mariano Loza-Coll, Greg Wray, Taku Hibino, Eric Röttinger, Allison M. Churcher, Annamaria Locascio, Arcady Mushegian, Masashi Kinukawa, Anna Reade, Katherine M. Buckley, I. R. Gibbons, Bert Gold, Aleksandar Milosavljevic, David Epel, Victor D. Vacquier, Ling Ling Pu, Vincenzo Cavalieri, Erin L. Allgood, Lan Zhang, Lynne V. Nazareth, Constantin N. Flytzanis, Ian Bosdet, Yi-Hsien Su, Zeev Pancer, Matthew L. Rowe, Robert C. Angerer, David R. McClay, William H. Klein, Rachel F. Gray, Julian L. Wong, Shunsuke Yaguchi, Robert Bellé, Aaron J. Mackey, Herath Jayantha Gunaratne, Karl Frederik Bergeron, Bruce P. Brandhorst, Greg Murray, Avis H. Cohen, Stephanie Bell, Kristin Tessmar-Raible, Ian K. Townley, Bertrand Cosson, Thomas D. Glenn, Jongmin Nam, Cynthia A. Bradham, Michael Dean, Joseph Chacko, Anthony J. Robertson, Margherita Branno, Valeria Matranga, K. James Durbin, Esther Miranda, Lili Chen, Eran Elhaik, Robert D. Burke, Rita A. Wright, Paola Oliveri, Sandra L. Lee, Gary W. Moy, Alexander E Primus, Shawn S. McCafferty, Cristina Calestani, David A. Garfield, Erica Sodergren, Karen Wilson, Joel Smith, Marco A. Marra, Cynthia Messier, Julia Morales, Kim D. Pruitt, Rachel Thorn, Rachel Gill, John S. Taylor, Mark E. Hahn, Victor Sapojnikov, Meredith Howard-Ashby, Lynne M. Angerer, Maurice R. Elphick, Kathy R. Foltz, Anne Marie Genevière, Justin T. Reese, Blanca E. Galindo, Kim C. Worley, Andrew Leone, Glen Humphrey, Kevin Berney, Olga Ermolaeva, George Miner, David P. Terwilliger, Elly Suk Hen Chow, Lora Lewis, Dan Graur, C. Titus Brown, Gerard Manning, Kevin J. Peterson, Angela Jolivet, Michele K. Anderson, Francesca Rizzo, Ekaterina Voronina, Thierry Lepage, Giorgio Matassi, Antonio Fernandez-Guerra, Mamoru Nomura, Charles A. Whittaker, James R.R. Whittle, James A. Coffman, George M. Weinstock, Mohammed M. Idris, Ashlan M. Musante, Sebastian D. Fugmann, Katherine D. Walton, Sorin Istrail, Shu-Yu Wu, Cerrissa Hamilton, Jonah Cool, Jacqueline E. Schein, Stacey M. Curry, Athula Wikramanayke, Seth Carbonneau, Blair J. Rossetti, Christopher E. Killian, Melissa J. Landrum, Amanda P. Rawson, Jenifer C. Croce, Ryan C. Range, Rahul Satija, John J. Stegeman, Yufeng Shen, Cavit Agca, Terry Gaasterland, Rocky Cheung, Takae Kiyama, Nikki Adams, Jonathan P. Rast, Robert Piotr Olinski, Andrew Cree, Mark Scally, Shuguang Liang, David A. Parker, Rebecca Thomason, Gretchen E. Hofmann, Michelle M. Roux, Ronghui Xu, Robert A. Obar, Enrique Arboleda, Odile Mulner-Lorillon, Shannon Dugan-Rocha, David J. Bottjer, Gabriele Amore, Manoj P. Samanta, Waraporn Tongprasit, Véronique Duboc, La Ronda Jackson, Fred H. Wilt, Viktor Stolc, Anna T. Neill, Michael Raisch, Pei Yun Lee, Jia L. Song, Margaret Morgan, Brian T. Livingston, Sofia Hussain, Zheng Wei, Bryan J. Cole, Tonya F. Severson, Victor V. Solovyev, Finn Hallböök, Donna M. Muzny, Christine A. Byrum, Albert J. Poustka, Xiuqian Mu, Andrew R. Jackson, Shin Heesun, Euan R. Brown, Nansheng Chen, Patrick Cormier, Ralph Haygood, Pedro Martinez, R. Andrew Cameron, D. Wang, Wendy S. Beane, Eric H. Davidson, Christie Kovar, Hemant Kelkar, Charles A. Ettensohn, Sham V. Nair, Robert L. Morris, Stefan C. Materna, Michael C. Thorndyke, Richard A. Gibbs, Dan O Mellott, Department of Physiology and Biophysics, Stony Brook University [The State University of New York] ( SBU ), Astronomy Unit ( AU ), Queen Mary University of London ( QMUL ), Urban and Industrial Air Quality Group, CSIRO Energy Technology, Commonwealth Scientific and Industrial Research Organisation Energy Technology ( CSIRO Energy Technology ), Commonwealth Scientific and Industrial Research Organisation, Center for Polymer Studies ( CPS ), Boston University [Boston] ( BU ), Physics Department [Boston] ( BU-Physics ), Max Planck Institute for Psycholinguistics, Max-Planck-Institut, Department of Biology [Norton], Wheaton College [Norton], Mathematical Institute [Oxford] ( MI ), University of Oxford [Oxford], Centre for the Analysis of Time Series ( CATS ), London School of Economics and Political Science ( LSE ), Thomas Jefferson National Accelerator Facility ( Jefferson Lab ), Thomas Jefferson National Accelerator Facility, Laboratoire d'Energétique et de Mécanique Théorique Appliquée ( LEMTA ), Université de Lorraine ( UL ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire Evolution, Génomes et Spéciation ( LEGS ), Centre National de la Recherche Scientifique ( CNRS ), Department of Geology, University of Illinois at Urbana-Champaign [Urbana], Department of Electrical and Computer Engineering [Portland] ( ECE ), Portland State University [Portland] ( PSU ), Saint-Gobain Crystals [USA], SAINT-GOBAIN, Institute for Animal Health ( IAH ), Biotechnology and Biological Sciences Research Council, Center for Agricultural Resources Research, Chinese Academy of Sciences [Changchun Branch] ( CAS ), Ipsen Inc. [Milford] ( Ipsen ), IPSEN, Department of Physics [Berkeley], University of California [Berkeley], Institute for Climate and Atmospheric Science [Leeds] ( ICAS ), University of Leeds, Chung-Ang University ( CAU ), Chung-Ang University [Seoul], Antarctic Climate and Ecosystems Cooperative Research Center ( ACE-CRC ), Institute of Aerodynamics and Fluid Mechanics ( AER ), Technische Universität München [München] ( TUM ), Mer et santé ( MS ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), Imperial College London, Radio and Atmospheric Sciences Division, National Physical Laboratory [Teddington] ( NPL ), International Research Institute for Climate and Society ( IRI ), Earth Institute at Columbia University, Columbia University [New York]-Columbia University [New York], Soils Group, The Macaulay Institute, Department of Haematology, University of Cambridge [UK] ( CAM ), School of Biology and Biochemistry, Queen's University, Leslie Hill Institute for Plant Conservation ( PCU ), University of Cape Town, Institute for Microelectronics and Microsystems/ Istituto per la Microelettronica e Microsistemi ( IMM ), Consiglio Nazionale delle Ricerche ( CNR ), Laboratoire d'acoustique de l'université du Mans ( LAUM ), Le Mans Université ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Interactive Systems Labs ( ISL ), Carnegie Mellon University [Pittsburgh] ( CMU ), Dalian Institute of Chemical Physics ( DICP ), Architectures, Languages and Compilers to Harness the End of Moore Years ( ALCHEMY ), Laboratoire de Recherche en Informatique ( LRI ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ) -Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique ( Inria ), Clean Air Task Force ( CATF ), Clean Air Task Force, Space Physics Laboratory, Indian Space Research Organisation ( ISRO ), Centre d'études et de recherches appliquées à la gestion ( CERAG ), Université Pierre Mendès France - Grenoble 2 ( UPMF ) -Centre National de la Recherche Scientifique ( CNRS ), Department of Microbiology and Immunology, College of Medicine and Health Sciences-Sultan Qaboos University, European Molecular Biology Laboratory [Heidelberg] ( EMBL ), Department of Biostatistics, University of Michigan [Ann Arbor], Department of Radiation Oncology [Michigan] ( Radonc ), Department of Physics and Astronomy [Leicester], University of Leicester, Informatique, Biologie Intégrative et Systèmes Complexes ( IBISC ), Université d'Évry-Val-d'Essonne ( UEVE ) -Centre National de la Recherche Scientifique ( CNRS ), Institut für Meteorologie und Klimaforschung ( IMK ), Karlsruher Institut für Technologie ( KIT ), Physics Department [UNB], University of New Brunswick ( UNB ), Laboratoire Parole et Langage ( LPL ), Centre National de la Recherche Scientifique ( CNRS ) -Aix Marseille Université ( AMU ), Institut des Sciences Chimiques de Rennes ( ISCR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Ecole Nationale Supérieure de Chimie de Rennes-Institut National des Sciences Appliquées ( INSA ) -Centre National de la Recherche Scientifique ( CNRS ), Biogéosciences [Dijon] ( BGS ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Bioprojet, Laboratoire de Matériaux à Porosité Contrôlée ( LMPC ), Université de Haute-Alsace (UHA) Mulhouse - Colmar ( Université de Haute-Alsace (UHA) ) -Ecole Nationale Supérieure de Chimie de Mulhouse-Centre National de la Recherche Scientifique ( CNRS ), School of Information Engineering [USTB] ( SIE ), University of Science and Technology Beijing [Beijing] ( USTB ), Laboratory for Atmospheric and Space Physics [Boulder] ( LASP ), University of Colorado Boulder [Boulder], Department of Applied Mathematics [Sheffield], University of Sheffield [Sheffield], School of Mathematics and Statistics [Sheffield] ( SoMaS ), Laboratoire de Mécanique de Lille - FRE 3723 ( LML ), Université de Lille, Sciences et Technologies-Ecole Centrale de Lille-Centre National de la Recherche Scientifique ( CNRS ), Computer Science Department [UCLA] ( CSD ), University of California at Los Angeles [Los Angeles] ( UCLA ), Développement et évolution ( DE ), Université Paris-Sud - Paris 11 ( UP11 ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Biologie du Développement de Villefranche sur mer ( LBDV ), Laboratoire Pierre Aigrain ( LPA ), Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris ( FRDPENS ), Centre National de la Recherche Scientifique ( CNRS ) -École normale supérieure - Paris ( ENS Paris ) -Centre National de la Recherche Scientifique ( CNRS ) -École normale supérieure - Paris ( ENS Paris ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Department of Mathematics and Statistics [Mac Gill], McGill University, Departamento de Botánica [Comahue], Universidad nacional del Comahue, Bioénergétique Cellulaire et Pathologique ( BECP ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Environnements et Paléoenvironnements OCéaniques ( EPOC ), Observatoire aquitain des sciences de l'univers ( OASU ), Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers ( INSU - CNRS ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers ( INSU - CNRS ) -Centre National de la Recherche Scientifique ( CNRS ) -École pratique des hautes études ( EPHE ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Jacques Monod ( IJM ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratori Nazionali del Sud ( LNS ), National Institute for Nuclear Physics ( INFN ), Departament de Matemàtiques [Barcelona], Universitat Autònoma de Barcelona [Barcelona] ( UAB ), Max-Planck-Institut für Kohlenforschung (coal research), Institute of Oceanology [CAS] ( IOCAS ), National Chiao Tung University ( NCTU ), Department of Hydrology and Water Resources ( HWR ), University of Arizona, Centre for Educational Technology, Environment Department [York], University of York [York, UK], State Key Laboratory of Nuclear Physics and Technology ( SKL-NPT ), Peking University [Beijing], Department of Physics and Astronomy [Iowa City], University of Iowa [Iowa], NASA Ames Research Center ( ARC ), Department of Materials, Digital Language & Knowledge Contents Research Association ( DICORA ), Hankuk University of Foreign Studies, Department of Physics [Coventry], University of Warwick [Coventry], Space Science and Technology Department [Didcot] ( RAL Space ), STFC Rutherford Appleton Laboratory ( RAL ), Science and Technology Facilities Council ( STFC ) -Science and Technology Facilities Council ( STFC ), Institut de biologie et chimie des protéines [Lyon] ( IBCP ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), H M Nautical Almanac Office [RAL] ( HMNAO ), Rutherford Appleton Laboratory, United Kingdom Met Office [Exeter], University College of London [London] ( UCL ), Department of Pathology and Laboratory Medicine [UCLA], University of California at Los Angeles [Los Angeles] ( UCLA ) -School of Medicine, School of Earth and Environmental Sciences [Seoul] ( SEES ), Seoul National University [Seoul], Department of Chemistry, Seoul Women's University, MicroMachines Centre ( MMC ), Nanyang Technological University [Singapour], Regroupement Québécois sur les Matériaux de Pointe ( RQMP ), École Polytechnique de Montréal ( EPM ) -Université de Sherbrooke [Sherbrooke]-McGill University-Université de Montréal-Fonds Québécois de Recherche sur la Nature et les Technologies ( FQRNT ), Département de Physique [Montréal], Université de Montréal, School of Earth and Environment [Leeds] ( SEE ), Centre for Ecology and Hydrology ( CEH ), Natural Environment Research Council ( NERC ), Norwegian Institute for Water Research ( NIVA ), Norwegian Institute for Water Research, Stony Brook University [SUNY] (SBU), State University of New York (SUNY)-State University of New York (SUNY), Astronomy Unit [London] (AU), Queen Mary University of London (QMUL), Commonwealth Scientific and Industrial Research Organisation Energy Technology (CSIRO Energy Technology), Commonwealth Scientific and Industrial Research Organisation [Canberra] (CSIRO), Department of Biochemistry and Molecular Biology [Houston], The University of Texas Medical School at Houston, Mathematical Institute [Oxford] (MI), University of Oxford, Centre for the Analysis of Time Series (CATS), London School of Economics and Political Science (LSE), Thomas Jefferson National Accelerator Facility (Jefferson Lab), Laboratoire Énergies et Mécanique Théorique et Appliquée (LEMTA ), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Evolution, Génomes et Spéciation (LEGS), Centre National de la Recherche Scientifique (CNRS), University of Illinois System-University of Illinois System, Department of Electrical and Computer Engineering [Portland] (ECE), Portland State University [Portland] (PSU), Saint-Gobain, Institute for Animal Health (IAH), Biotechnology and Biological Sciences Research Council (BBSRC), Chinese Academy of Sciences [Changchun Branch] (CAS), Ipsen Inc. [Milford] (Ipsen), University of California [Berkeley] (UC Berkeley), University of California (UC)-University of California (UC), Institute for Climate and Atmospheric Science [Leeds] (ICAS), School of Earth and Environment [Leeds] (SEE), University of Leeds-University of Leeds, Chung-Ang University (CAU), Antarctic Climate and Ecosystems Cooperative Research Centre (ACE-CRC), Institute of Aerodynamics and Fluid Mechanics (AER), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Mer et santé (MS), Station biologique de Roscoff [Roscoff] (SBR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), National Physical Laboratory [Teddington] (NPL), International Research Institute for Climate and Society (IRI), Macaulay Institute, University of Cambridge [UK] (CAM), Queen's University [Kingston, Canada], Leslie Hill Institute for Plant Conservation (PCU), Istituto per la Microelettronica e Microsistemi [Catania] (IMM), National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR), Laboratoire d'Acoustique de l'Université du Mans (LAUM), Le Mans Université (UM)-Centre National de la Recherche Scientifique (CNRS), Interactive Systems Labs (ISL), Carnegie Mellon University [Pittsburgh] (CMU), Dalian Institute of Chemical Physics (DICP), Architectures, Languages and Compilers to Harness the End of Moore Years (ALCHEMY), Laboratoire de Recherche en Informatique (LRI), Université Paris-Sud - Paris 11 (UP11)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Clean Air Task Force (CATF), Indian Space Research Organisation (ISRO), Centre d'études et de recherches appliquées à la gestion (CERAG), Université Pierre Mendès France - Grenoble 2 (UPMF)-Centre National de la Recherche Scientifique (CNRS), Sultan Qaboos University (SQU)-College of Medicine and Health Sciences [Baylor], Baylor University-Baylor University, European Molecular Biology Laboratory [Heidelberg] (EMBL), University of Michigan System-University of Michigan System, Department of Radiation Oncology [Michigan] (Radonc), Informatique, Biologie Intégrative et Systèmes Complexes (IBISC), Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Institute for Meteorology and Climate Research (IMK), Karlsruhe Institute of Technology (KIT), University of New Brunswick (UNB), Laboratoire Parole et Langage (LPL), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Biogéosciences [UMR 6282] (BGS), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Matériaux à Porosité Contrôlée (LMPC), Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS), School of Information Engineering [USTB] (SIE), University of Science and Technology Beijing [Beijing] (USTB), Laboratory for Atmospheric and Space Physics [Boulder] (LASP), University of Colorado [Boulder], School of Mathematics and Statistics [Sheffield] (SoMaS), Laboratoire de Mécanique de Lille - FRE 3723 (LML), Université de Lille, Sciences et Technologies-Centrale Lille-Centre National de la Recherche Scientifique (CNRS), Computer Science Department [UCLA] (CSD), University of California [Los Angeles] (UCLA), Développement et évolution (DE), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biologie du Développement de Villefranche sur mer (LBDV), Observatoire océanologique de Villefranche-sur-mer (OOVM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Pierre Aigrain (LPA), Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Department of Mathematics and Statistics [Montréal], McGill University = Université McGill [Montréal, Canada], Departamento de Botánica [Bariloche], Centro Regional Universitario Bariloche [Bariloche] (CRUB), Universidad Nacional del Comahue [Neuquén] (UNCOMA)-Universidad Nacional del Comahue [Neuquén] (UNCOMA), Bioénergétique Cellulaire et Pathologique (BECP), Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Environnements et Paléoenvironnements OCéaniques (EPOC), Observatoire aquitain des sciences de l'univers (OASU), Université Sciences et Technologies - Bordeaux 1 (UB)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1 (UB)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Laboratori Nazionali del Sud (LNS), Istituto Nazionale di Fisica Nucleare (INFN), Departament de Matemàtiques [Barcelona] (UAB), Universitat Autònoma de Barcelona (UAB), Max-Planck-Institut für Kohlenforschung (Coal Research), Max-Planck-Gesellschaft, CAS Institute of Oceanology (IOCAS), Chinese Academy of Sciences [Beijing] (CAS), National Chiao Tung University (NCTU), Department of Hydrology and Water Resources (HWR), State Key Laboratory of Nuclear Physics and Technology (SKL-NPT), University of Iowa [Iowa City], NASA Ames Research Center (ARC), Digital Language & Knowledge Contents Research Association (DICORA), Space Science and Technology Department [Didcot] (RAL Space), STFC Rutherford Appleton Laboratory (RAL), Science and Technology Facilities Council (STFC)-Science and Technology Facilities Council (STFC), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), H M Nautical Almanac Office [RAL] (HMNAO), University College of London [London] (UCL), University of California (UC)-University of California (UC)-School of Medicine, School of Earth and Environmental Sciences [Seoul] (SEES), Seoul National University [Seoul] (SNU), MicroMachines Centre (MMC), Regroupement Québécois sur les Matériaux de Pointe (RQMP), École Polytechnique de Montréal (EPM)-Université de Sherbrooke (UdeS)-McGill University = Université McGill [Montréal, Canada]-Université de Montréal (UdeM)-Fonds Québécois de Recherche sur la Nature et les Technologies (FQRNT), Université de Montréal (UdeM), Centre for Ecology and Hydrology (CEH), Natural Environment Research Council (NERC), Norwegian Institute for Water Research (NIVA), SEA URCHIN GENOME SEQUENCING CONSORTIUM, SODERGREN E, WEINSTOCK GM, DAVIDSON EH, CAMERON RA, GIBBS RA, ANGERER RC, ANGERER LM, ARNONE MI, BURGESS DR, BURKE RD, COFFMAN JA, DEAN M, ELPHICK MR, ETTENSOHN CA, FOLTZ KR, HAMDOUN A, HYNES RO, KLEIN WH, MARZLUFF W, MCCLAY DR, MORRIS RL, MUSHEGIAN A, RAST JP, SMITH LC, THORNDYKE MC, VACQUIER VD, WESSEL GM, WRAY G, ZHANG L, ELSIK CG, ERMOLAEVA O, HLAVINA W, HOFMANN G, KITTS P, LANDRUM MJ, MACKEY AJ, MAGLOTT D, PANOPOULOU G, POUSTKA AJ, PRUITT K, SAPOJNIKOV V, SONG X, SOUVOROV A, SOLOVYEV V, WEI Z, WHITTAKER CA, WORLEY K, DURBIN KJ, SHEN Y, FEDRIGO O, GARFIELD D, HAYGOOD R, PRIMUS A, SATIJA R, SEVERSON T, GONZALEZ-GARAY ML, JACKSON AR, MILOSAVLJEVIC A, TONG M, KILLIAN CE, LIVINGSTON BT, WILT FH, ADAMS N, BELLE R, CARBONNEAU S, CHEUNG R, CORMIER P, COSSON B, CROCE J, FERNANDEZ-GUERRA A, GENEVIERE AM, GOEL M, KELKAR H, MORALES J, MULNER-LORILLON O, ROBERTSON AJ, GOLDSTONE JV, COLE B, EPEL D, GOLD B, HAHN ME, HOWARD-ASHBY M, SCALLY M, STEGEMAN JJ, ALLGOOD EL, COOL J, JUDKINS KM, MCCAFFERTY SS, MUSANTE AM, OBAR RA, RAWSON AP, ROSSETTI BJ, GIBBONS IR, HOFFMAN MP, LEONE A, ISTRAIL S, MATERNA SC, SAMANTA MP, STOLC V, TONGPRASIT W, TU Q, BERGERON KF, BRANDHORST BP, WHITTLE J, BERNEY K, BOTTJER DJ, CALESTANI C, PETERSON K, CHOW E, YUAN QA, ELHAIK E, GRAUR D, REESE JT, BOSDET I, HEESUN S, MARRA MA, SCHEIN J, ANDERSON MK, BROCKTON V, BUCKLEY KM, COHEN AH, FUGMANN SD, HIBINO T, LOZA-COLL M, MAJESKE AJ, MESSIER C, NAIR SV, PANCER Z, TERWILLIGER DP, AGCA C, ARBOLEDA E, CHEN N, CHURCHER AM, HALLBOOK F, HUMPHREY GW, IDRIS MM, KIYAMA T, LIANG S, MELLOTT D, MU X, MURRAY G, OLINSKI RP, RAIBLE F, ROWE M, TAYLOR JS, TESSMAR-RAIBLE K, WANG D, WILSON KH, YAGUCHI S, GAASTERLAND T, GALINDO BE, GUNARATNE HJ, JULIANO C, KINUKAWA M, MOY GW, NEILL AT, NOMURA M, RAISCH M, READE A, ROUX MM, SONG JL, SU YH, TOWNLEY IK, VORONINA E, WONG JL, AMORE G, BRANNO M, BROWN ER, CAVALIERI, V, DUBOC V, DULOQUIN L, FLYTZANIS C, GACHE C, LAPRAZ F, LEPAGE T, LOCASCIO A, MART, University of California-University of California, Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Consiglio Nazionale delle Ricerche (CNR), Centre National de la Recherche Scientifique (CNRS)-Le Mans Université (UM), Centre National de la Recherche Scientifique (CNRS)-Université Pierre Mendès France - Grenoble 2 (UPMF), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Biogéosciences [UMR 6282] [Dijon] (BGS), Centre National de la Recherche Scientifique (CNRS)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Ecole Nationale Supérieure de Chimie de Mulhouse-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-École pratique des hautes études (EPHE), University of California-University of California-School of Medicine, Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Université de Lille, Sciences et Technologies-Centre National de la Recherche Scientifique (CNRS)-Centrale Lille, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF), University of Manchester Institute of Science and Technology (UMIST), Condensed Matter Physics and Materials Science Department, Brookhaven National Laboratory, Brookhaven National Laboratory [Upton, NY] (BNL), UT-Battelle, LLC-Stony Brook University [SUNY] (SBU), State University of New York (SUNY)-State University of New York (SUNY)-U.S. Department of Energy [Washington] (DOE)-UT-Battelle, LLC-Stony Brook University [SUNY] (SBU), State University of New York (SUNY)-State University of New York (SUNY)-U.S. Department of Energy [Washington] (DOE), Baylor College of Medicine (BCM), Baylor University, Laboratoire de Traitement de l'Information Medicale (LaTIM), Université européenne de Bretagne - European University of Brittany (UEB)-Université de Brest (UBO)-Télécom Bretagne-Institut Mines-Télécom [Paris] (IMT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Laboratoire de Modélisation et Simulation Multi Echelle (MSME), Université Paris-Est Marne-la-Vallée (UPEM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Duke University [Durham], Instituto Andaluz de Geofísica y Prevención de Desastres Sísmicos [Granada] (IAGPDS), Universidad de Granada (UGR), Laboratoire d'Ingénierie des Matériaux de Bretagne (LIMATB), Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Université de Brest (UBO), University of New South Wales [Sydney] (UNSW), Celera Genomics (CRA), Celera Genomics, Paléobiodiversité et paléoenvironnements, Muséum national d'Histoire naturelle (MNHN)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Roma Tor Vergata [Roma], Unité de recherches forestières (BORDX PIERR UR ), Institut National de la Recherche Agronomique (INRA), Deptartment of Neuroscience, Uppsala University, State Key Laboratory of Palaeobiology and Stratigraphy, Nanjing Institute of Geology and Palaeontology (NIGPAS-CAS), Chinese Academy of Sciences [Nanjing Branch]-Chinese Academy of Sciences [Nanjing Branch], Institut Méditerranéen d'Ecologie et de Paléoécologie (IMEP), Université Paul Cézanne - Aix-Marseille 3-Université de Provence - Aix-Marseille 1-Avignon Université (AU)-Centre National de la Recherche Scientifique (CNRS), Key Laboratory of Ocean Circulation and Waves, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China, Université Paris Diderot - Paris 7 (UPD7), Department of Physical and Environmental Sciences [Toronto], University of Toronto at Scarborough, inconnu temporaire UPEMLV, Inconnu, Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Department of Atmospheric Sciences [Seattle], University of Washington [Seattle], National Institute of Advanced Industrial Science and Technology (AIST), Department of Pharmacy, Università degli studi di Genova = University of Genoa (UniGe), Interdisciplinary Arts and Sciences Department, St. Vincent's Hospital, Sydney, Laboratoire des Sciences de l'Environnement Marin (LEMAR) (LEMAR), Institut de Recherche pour le Développement (IRD)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Brest (UBO)-Institut Universitaire Européen de la Mer (IUEM), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Department of Electrical Engineering (DEE-POSTECH), Pohang University of Science and Technology (POSTECH), Centre Suisse d'Electronique et de Microtechnique SA [Neuchatel] (CSEM), Centre Suisse d'Electronique et Microtechnique SA (CSEM), Human Genome Sequencing Center [Houston] (HGSC), Brookhaven National Laboratory, Meteorological Service of Canada, 4905 Dufferin Street, Université européenne de Bretagne - European University of Brittany (UEB)-Télécom Bretagne-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Mines-Télécom [Paris] (IMT), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Université Paris-Est Marne-la-Vallée (UPEM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherches Forestières, Department of Physical and Environmental Sciences, University of Toronto [Scarborough, Canada], National Institute for Nuclear Physics (INFN), University of Genoa (UNIGE), Institut de Recherche pour le Développement (IRD)-Institut Universitaire Européen de la Mer (IUEM), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Université de Brest (UBO)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS), Universidad de Granada = University of Granada (UGR), Laboratoire d'Energétique et de Mécanique Théorique Appliquée (LEMTA ), Technische Universität München [München] (TUM), Queen's University [Kingston], Centre National de la Recherche Scientifique (CNRS)-Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Grenoble Alpes (UGA), Institut für Meteorologie und Klimaforschung (IMK), Karlsruher Institut für Technologie (KIT), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Rennes-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES), Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Sciences et Technologies-Ecole Centrale de Lille-Université de Lille, Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-École pratique des hautes études (EPHE)-Centre National de la Recherche Scientifique (CNRS), Universitat Autònoma de Barcelona [Barcelona] (UAB), École Polytechnique de Montréal (EPM)-Université de Sherbrooke [Sherbrooke]-Université de Montréal [Montréal]-McGill University-Fonds Québécois de Recherche sur la Nature et les Technologies (FQRNT), Université de Montréal [Montréal], U.S. Department of Energy [Washington] (DOE)-UT-Battelle, LLC-Stony Brook University [SUNY] (SBU), Université de Bretagne Sud (UBS)-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Université de Brest (UBO)-Université de Brest (UBO), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Paul Cézanne - Aix-Marseille 3-Centre National de la Recherche Scientifique (CNRS)-Avignon Université (AU)-Université de Provence - Aix-Marseille 1, Institut Universitaire Européen de la Mer (IUEM), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS)-Université de Brest (UBO), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université de Lille, Sciences et Technologies-Ecole Centrale de Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Paris (ENS Paris), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, MESH: Signal Transduction, MESH: Sequence Analysis, DNA, MESH : Transcription Factors, MESH : Calcification, Physiologic, Genome, MESH : Proteins, 0302 clinical medicine, MESH : Embryonic Development, MESH: Gene Expression Regulation, Developmental, Innate, MESH: Embryonic Development, Developmental, Nervous System Physiological Phenomena, MESH: Animals, MESH: Proteins, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Complement Activation, ComputingMilieux_MISCELLANEOUS, MESH: Evolution, Molecular, MESH : Strongylocentrotus purpuratus, Genetics, 0303 health sciences, MESH: Nervous System Physiological Phenomena, Multidisciplinary, biology, Medicine (all), MESH: Immunologic Factors, Gene Expression Regulation, Developmental, Genome project, MESH: Transcription Factors, MESH : Immunity, Innate, MESH : Complement Activation, MESH: Genes, Bacterial artificial chromosome (BAC)DeuterostomesStrongylocentrotus purpuratusVertebrate innovations, Echinoderm, MESH : Nervous System Physiological Phenomena, embryonic structures, MESH: Cell Adhesion Molecules, MESH : Genes, MESH: Immunity, Innate, Sequence Analysis, Signal Transduction, MESH: Computational Biology, Genome evolution, MESH: Complement Activation, Sequence analysis, Evolution, MESH: Strongylocentrotus purpuratus, MESH : Male, Embryonic Development, MESH : Immunologic Factors, Article, MESH: Calcification, Physiologic, Calcification, MESH : Cell Adhesion Molecules, Evolution, Molecular, 03 medical and health sciences, Calcification, Physiologic, Animals, Immunologic Factors, MESH: Genome, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH : Evolution, Molecular, Physiologic, Gene, Strongylocentrotus purpuratus, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, MESH : Signal Transduction, Bacterial artificial chromosome, Immunity, Molecular, Computational Biology, Proteins, Cell Adhesion Molecules, Genes, Immunity, Innate, Transcription Factors, Sequence Analysis, DNA, DNA, biology.organism_classification, MESH: Male, Gene Expression Regulation, MESH : Animals, MESH : Gene Expression Regulation, Developmental, MESH : Genome, 030217 neurology & neurosurgery, MESH : Computational Biology, MESH : Sequence Analysis, DNA
Abstract

We report the sequence and analysis of the 814-megabase genome of the sea urchin Strongylocentrotus purpuratus , a model for developmental and systems biology. The sequencing strategy combined whole-genome shotgun and bacterial artificial chromosome (BAC) sequences. This use of BAC clones, aided by a pooling strategy, overcame difficulties associated with high heterozygosity of the genome. The genome encodes about 23,300 genes, including many previously thought to be vertebrate innovations or known only outside the deuterostomes. This echinoderm genome provides an evolutionary outgroup for the chordates and yields insights into the evolution of deuterostomes.

Published
2006
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38. Insights into social insects from the genome of the honeybee Apis mellifera

Author

George M. Weinstock, Andrew K. Jones, Katherine A Aronstein, Irene Gattermeier, Kiyoshi Kimura, Susan E. Fahrbach, Laura I. Decanini, Christina M. Grozinger, Evgeny M. Zdobnov, Susan J. Brown, Jonathan V. Sweedler, Kazutoyo Osoegawa, Christian A. Ross, Joseph J. Gillespie, Ngoc Nguyen, Geert Baggerman, Frank Hauser, Dan Graur, Michelle M. Elekonich, Alison R. Mercer, Amanda F. Svatek, Jean Marie Cornuet, Cornelis J. P. Grimmelikhuijzen, Aleksandar Milosavljevic, Anand Venkatraman, Andrew J. Schroeder, Huaiyang Jiang, Michael R. Kanost, Justin T. Reese, Margaret Morgan, Tomoko Fujiyuki, Kim C. Worley, Susanta K. Behura, Jun Kawai, Robert Kucharski, Gildardo Aquino-Perez, Miguel Corona, Diana E. Wheeler, Kathryn S. Campbell, William M. Gelbart, Amy L. Toth, Yanping Chen, Mira Cohen, Noam Kaplan, Michihira Tagami, Miguel A. Peinado, Peter K. Dearden, Glenford Savery, Liliane Schoofs, Takeo Kubo, Giuseppe Cazzamali, Sylvain Forêt, Thomas C. Newman, Ross Overbeek, Piero Carninci, Ryszard Maleszka, Barbara J. Ruef, Michal Linial, Alexandre S. Cristino, Mary A. Schuler, Huyen Dinh, J. Troy Littleton, Manoj P. Samanta, Waraporn Tongprasit, L. Sian Grametes, Eran Elhaik, Jean-Luc Imler, Zhen Zou, Rodrigo A. Velarde, Tanja Gempe, Dorothea Eisenhardt, Juan Manuel Anzola, Graham J. Thompson, Aaron J. Mackey, René Feyereisen, Mrcia M.G. Bitondi, Lora Lewis, Guy Bloch, Richard A. Gibbs, Jane Peterson, Jay D. Evans, Robert E. Page, Amanda B. Hummon, Viktor Stolc, Donna M. Muzny, Yair Shemesh, Francis M. F. Nunes, Dawn Lopez, Judith H. Willis, Martin Hasselmann, Mark S. Guyer, John G. Oakeshott, Pinglei Zhou, Eriko Kage, Dominique Vautrin, Kevin J. Hackett, Sandra L. Lee, Clay Davis, Christine Emore, Gene E. Robinson, Alexandre Souvorov, T.A. Richmond, Rachel Thorn, Jurgen Huybrechts, Elad B. Rubin, Craig Mizzen, Deborah R. Smith, Walter S. Sheppard, Takekazu Kunieda, Adam Felsenfeld, Bingshan Li, Jeffrey G. Reid, La Ronda Jackson, Jamie J. Cannone, Robin R. Gutell, Jireh Santibanez, Megan J. Wilson, David B. Sattelle, Azusa Kamikouchi, George Miner, Hideaki Takeuchi, Geoffrey Okwuonu, Jennifer Hume, Jonathan Miller, Kazuaki Ohashi, Angela Jovilet, Yoshihide Hayashizaki, Joseph Chacko, Paul Kitts, Erica Sodergren, Charles Hetru, Andrew V. Suarez, Brian P. Lazzaro, Susan E. St. Pierre, Evy Vierstraete, Haobo Jiang, Sandra Hines, Teresa D. Shippy, Greg J. Hunt, Peter Kosarev, Dan Hultmark, Stefan Albert, Susan M. Russo, Chung Li Shu, Michel Solignac, H. Michael G. Lattorff, Xu Ling, Grard Leboulle, Miklós Csürös, Neil D. Tsutsui, Lynne V. Nazareth, Ying Wang, Florence Mougel, Beverly B. Matthews, Kevin L. Childs, Rita A. Wright, Hugh M. Robertson, Lan Zhang, Peter Verleyen, Daniel B. Weaver, Christie Kovar, Chikatoshi Kai, Charles W. Whitfield, Madeline A. Crosby, Natalia V. Milshina, Reed M. Johnson, Michael A. Ewing, Peter L. Jones, Sandra L. Rodriguez-Zas, Michael B. Eisen, Klaus Hartfelder, Karl H.J. Gordon, W. Augustine Dunn, Ling Ling Pu, M. Monnerot, Stephen Richards, Richa Agarwala, Judith Hernandez, Pieter J. de Jong, Michael Williamson, Marcé D. Lorenzen, Zilá Luz Paulino Simões, Mark D. Drapeau, Donna Villasana, Katarína Bíliková, J. Spencer Johnston, David I. Schlipalius, Xuehong Wei, Laurent Duret, Venky N. Iyer, Andrew G. Clark, Christine G. Elsik, Hilary Ranson, Kyle T. Beggs, Mireia Jordà, Shiro Fukuda, Seth A. Ament, Vivek Iyer, Jozef Šimúth, Stewart H. Berlocher, May R. Berenbaum, Robin F. A. Moritz, Tatsuhiko Kadowaki, Charles Claudianos, Gro V. Amdam, Yue Liu, Naoko Sakazume, Morten Schioett, Paul Havlak, Anita M. Collins, Dirk C. de Graaf, Derek Collinge, Ivica Letunic, Carlos H. Lobo, Mizue Morioka, Martin Beye, Rachel Gill, C. Michael Dickens, Daisuke Sasaki, Victor V. Solovyev, Peer Bork, Sunita Biswas, David A. Wheeler, Heidi Paul, Bioinformatique, phylogénie et génomique évolutive (BPGE), Département PEGASE [LBBE] (PEGASE), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Evolution, Génomes et Spéciation (LEGS), Centre National de la Recherche Scientifique (CNRS), and Physical and genetic mapping

Subjects
Male, 0106 biological sciences, Transposable element, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], Proteome, Genome, Insect, Molecular Sequence Data, Genes, Insect, Genomics, Biology, 010603 evolutionary biology, 01 natural sciences, Genome, Article, Evolution, Molecular, 03 medical and health sciences, Molecular evolution, Phylogenetics, Animals, Gene, Phylogeny, abeille domestique, 030304 developmental biology, Whole genome sequencing, Genetics, Base Composition, 0303 health sciences, [SDV.GEN]Life Sciences [q-bio]/Genetics, Multidisciplinary, Behavior, Animal, Reproduction, SOCIAL BEHAVIOR, [SDV.BA]Life Sciences [q-bio]/Animal biology, Immunity, APIS MELLIFERA, food and beverages, Bees, Telomere, Physical Chromosome Mapping, INSECTE, Gene Expression Regulation, DNA methylation, DNA Transposable Elements, Female, GENETIQUE DES POPULATIONS, Signal Transduction
Abstract

Ce travail résulte de la collaboration de très nombreux chercheurs. Seuls les auteurs de la rubrique Physical and Genetic Mapping sont cités explicitement.; Here we report the genome sequence of the honeybee Apis mellifera, a key model for social behaviour and essential to global ecology through pollination. Compared with other sequenced insect genomes, the A. mellifera genome has high A1T and CpG contents, lacks major transposon families, evolves more slowly, and is more similar to vertebrates for circadian rhythm, RNA interference and DNA methylation genes, among others. Furthermore, A.mellifera has fewer genes for innate immunity, detoxification enzymes, cuticle-forming proteins and gustatory receptors, more genes for odorant receptors, and novel genes for nectar and pollen utilization, consistent with its ecology and social organization. Compared to Drosophila, genes in early developmental pathways differ in Apis, whereas similarities exist for functions that differ markedly, such as sex determination, brain function and behaviour. Population genetics suggests a novel African origin for the species A.mellifera and insights into whether Africanized bees spread throughout the New World via hybridization or displacement

Published
2006
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39. Genome-wide transcription analyses in rice using tiling microarrays

Author

Lei Li, Xing Wang Deng, Waraporn Tongprasit, Xiangfeng Wang, Xueyong Li, Viktor Stolc, Songgang Li, Dongfen Zhang, Zhukuan Cheng, Jun Wang, and Ning Su

Subjects
Genetics, Expressed Sequence Tags, Expressed sequence tag, Oryza sativa, Models, Genetic, Transcription, Genetic, food and beverages, Chromosome, Oryza, Biology, Genome, Homology (biology), Chromosomes, Intergenic region, Gene Expression Regulation, Plant, Tandem Repeat Sequences, DNA, Intergenic, DNA microarray, Gene, Genome, Plant, Oligonucleotide Array Sequence Analysis
Abstract

Sequencing and computational annotation revealed several features, including high gene numbers, unusual composition of the predicted genes and a large number of genes lacking homology to known genes, that distinguish the rice (Oryza sativa) genome from that of other fully sequenced model species. We report here a full-genome transcription analysis of the indica rice subspecies using high-density oligonucleotide tiling microarrays. Our results provided expression data support for the existence of 35,970 (81.9%) annotated gene models and identified 5,464 unique transcribed intergenic regions that share similar compositional properties with the annotated exons and have significant homology to other plant proteins. Elucidating and mapping of all transcribed regions revealed an association between global transcription and cytological chromosome features, and an overall similarity of transcriptional activity between duplicated segments of the genome. Collectively, our results provide the first whole-genome transcription map useful for further understanding the rice genome. Udgivelsesdato: 2006-Jan

Published
2005
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40. Global identification of human transcribed sequences with genome tiling arrays

Author

Alexander E. Urban, Paul Bertone, Michael Snyder, Xiaowei Zhu, Sherman M. Weissman, Mark Gerstein, Joel Rozowsky, John L. Rinn, Thomas Royce, Manoj P. Samanta, Waraporn Tongprasit, and Viktor Stolc

Subjects
DNA, Complementary, Transcription, Genetic, Computational biology, Biology, Genome, Conserved sequence, Mice, Intergenic region, Sequence Homology, Nucleic Acid, Databases, Genetic, Animals, Humans, RNA, Messenger, Gene, Conserved Sequence, Oligonucleotide Array Sequence Analysis, Genetics, Multidisciplinary, Tiling array, Base Sequence, Genome, Human, Reverse Transcriptase Polymerase Chain Reaction, Computational Biology, Nucleic Acid Hybridization, Proteins, Reproducibility of Results, Genome project, Exons, Introns, Human genome, CpG Islands, DNA, Intergenic, DNA microarray, Oligonucleotide Probes
Abstract

Elucidating the transcribed regions of the genome constitutes a fundamental aspect of human biology, yet this remains an outstanding problem. To comprehensively identify coding sequences, we constructed a series of high-density oligonucleotide tiling arrays representing sense and antisense strands of the entire nonrepetitive sequence of the human genome. Transcribed sequences were located across the genome via hybridization to complementary DNA samples, reverse-transcribed from polyadenylated RNA obtained from human liver tissue. In addition to identifying many known and predicted genes, we found 10,595 transcribed sequences not detected by other methods. A large fraction of these are located in intergenic regions distal from previously annotated genes and exhibit significant homology to other mammalian proteins.

Published
2004

41. Towards an MD simulation of ion currents in the alpha hemolysin channel

Author

James OKeeffe, Viktor Stolc, and Ioana Cozmuta

Subjects
chemistry.chemical_classification, chemistry, Chemical physics, Computational chemistry, Electric field, Molecular biophysics, Nucleic acid, Ionic bonding, Ion current, Polymer, Macromolecule, Ion
Abstract

Experiments show that single stranded nucleic acids polymers can be transported across an alpha hemolysin channel under the action of an applied electric field. The translocation of the nucleic acid polymers causes transient blockades in the ion current. The physical and chemical details of the interactions between polymer, channel and ionic solution that lead to the blockade events are not yet fully understood. Atomistic simulations enable a realistic description of the dynamic motions of the solvated polymer-pore system as a function of time. Analysis of such calculated system trajectories leads to valuable insight possible energy barriers, ion mobilities and short time-scale interactions. This study investigates the relationship between the structural properties of the alpha hemolysin channel and the ionic current blockades that result from the translocation of single stranded nucleic acids.

Published
2004
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42. Functional profiling of a human cytomegalovirus genome

Author

Walter Dunn, David A. Patterson, Viktor Stolc, Rong Hai, Hong Li, Hua Zhu, Cassie Chou, and Fenyong Liu

Subjects
Human cytomegalovirus, Chromosomes, Artificial, Bacterial, viruses, Population, Molecular Sequence Data, Clone (cell biology), Cytomegalovirus, Genome, Viral, Biology, Virus Replication, Open Reading Frames, medicine, Humans, ORFS, education, Gene, Tropism, Genetics, education.field_of_study, Multidisciplinary, Gene Expression Profiling, Biological Sciences, medicine.disease, Virology, Gene expression profiling, Viral replication, Mutagenesis, DNA, Viral, Gene Deletion
Abstract

Human cytomegalovirus (HCMV), a ubiquitous herpesvirus, causes a lifelong subclinical infection in healthy adults but leads to significant morbidity and mortality in neonates and immunocompromised individuals. Its ability to grow in different cell types is responsible for HCMV-associated diseases, including mental retardation and retinitis, and vascular disorders. To globally assess viral gene function for replication in cells, we determined the genomic sequence of a bacterial artificial chromosome (BAC)-based clone of HCMV Towne strain and used this information to delete each of its 162 unique ORFs and generate a collection of viral mutants. The growth of these mutants in different cultured cells was examined to systematically investigate the necessity of each ORF for replication. Our results showed that 45 ORFs are essential for viral replication in fibroblasts and 117 are nonessential. Some genes were found to be required for viral replication in retinal pigment epithelial cells and microvascular endothelial cells, but not in fibroblasts, indicating their role as tropism factors. Interestingly, several viral mutants grew 10- to 500-fold better than the parental strain in different cell types, suggesting that the deleted ORFs encode replication temperance or repressing functions. Thus, HCMV encodes supportive and suppressive growth regulators for optimizing its replication in human fibroblasts, epithelial, and endothelial cells. Suppression of viral replication by virus-encoded temperance factors represents a novel mechanism for regulating the growth of an animal virus, and may contribute to HCMV's optimal infection of different tissues and successful proliferation among the human population.

Published
2003

43. Polymer translocation through a nanopore: a geometry dependence study

Author

Viktor Stolc, Ioana Cozmuta, and James OKeeffe

Subjects
chemistry.chemical_classification, Physics::Biological Physics, Quantitative Biology::Biomolecules, Drift velocity, Chemistry, Diffusion, Dynamics (mechanics), Geometry, Polymer, Radius, Electrostatics, Condensed Matter::Soft Condensed Matter, Quantitative Biology::Subcellular Processes, Nanopore, Electric field
Abstract

The translocation of a single stranded nucleic acid polymer through a nanopore, by an external electric field applied across the pore, may be well described by a 1-D drift-diffusion model. Translocation times and velocities are calculated for a homopolymer driven through a nanopore, where the polymer-pore interaction dominates the polymer dynamics. In this model a purely electrostatic polymer-pore interaction is introduced, calculated from atomic charges on the polymer and pore. Simulation results show that the peak repulsion force occurs on the polymer during entry into the pore. In addition, the peak polymer-pore interaction is shown to decrease with polymer length for homopolymers with less than 20 nucleotides. The modeling results offer an explanation for the enhanced drift velocities experimentally observed for such short polymers. The dependence of the polymer translocation time on the pore geometry is investigated. For increasing pore radius the translocation velocity approaches the free space drift velocity for the surrounding ionic solution.

Published
2003
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44. Pyrosequencing

Author

Mostafa Ronaghi, Viktor Stolc, and Nader Pourmand

Subjects
Massive parallel sequencing, Pyrosequencing, Computational biology, Biology, DNA sequencing
Published
2001
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45. Characterization of two scleroderma autoimmune antigens that copurify with human ribonuclease P

Author

Viktor Stolc, Ramesh Kekuda, Sidney Altman, and Paul S. Eder

Subjects
RNase P, Protein subunit, Immunoblotting, Molecular Sequence Data, Biology, Molecular cloning, Cross Reactions, Autoantigens, Ribonuclease P, Antigen, Complementary DNA, Endoribonucleases, medicine, Humans, RNA, Catalytic, Amino Acid Sequence, Cloning, Molecular, Autoimmune disease, Multidisciplinary, Scleroderma, Systemic, Base Sequence, Nuclear RNase P, RNA, Sequence Analysis, DNA, Biological Sciences, medicine.disease, Molecular biology, Precipitin Tests, HeLa Cells
Abstract

Human RNase P has been purified more than 2000-fold from HeLa cells. In addition to the RNA component, H1 RNA, polypeptides of molecular masses 14, 20, 25, 30, 38, and 40 kDa copurify with the enzyme activity. Sera from two different patients with the autoimmune disease scleroderma were used to immunodeplete human RNase P activity. These same sera cross-reacted on immunoblots with two of the copurifying polypeptides, p30 and p38, whereas an autoimmune serum that does not immunodeplete RNase P activity did not react with these proteins. Peptide fragments derived from purified p30 and p38 facilitated the molecular cloning and sequencing of cDNAs coding for these two polypeptides, which are now designated as Rpp30 and Rpp38, respectively. RPP38 cDNA encodes a polypeptide that may be identical to a previously identified antigen of ≈40 kDa, which is immunoprecipitated by Th and To autoimmune antisera, and that has been implicated as a protein subunit of human RNase P by virtue of its ability to bind to H1 RNA in vitro . The second autoimmune antigen, Rpp30, as such, has not been described previously.

Published
1997

46. [Untitled]

Author

Lei Li, Songgang Li, Xiping Wang, Jun-Jun Wang, Viktor Stolc, Mian Xia, Ning Su, Xiangfeng Wang, Zhiyu Peng, and Xing Wang Deng

Subjects
2. Zero hunger, 0106 biological sciences, Genetics, 0303 health sciences, Euchromatin, Microarray analysis techniques, Heterochromatin, food and beverages, Genome project, Biology, 01 natural sciences, Genome, Gene expression profiling, 03 medical and health sciences, DNA microarray, Gene, 030304 developmental biology, 010606 plant biology & botany
Abstract

Background: Sequencing and annotation of the genome of rice (Oryza sativa) have generated gene models in numbers that top all other fully sequenced species, with many lacking recognizable sequence homology to known genes. Experimental evaluation of these gene models and identification of new models will facilitate rice genome annotation and the application of this knowledge to other more complex cereal genomes. Results: We report here an analysis of the chromosome 10 transcriptome of the two major rice subspecies, japonica and indica, using oligonucleotide tiling microarrays. This analysis detected expression of approximately three-quarters of the gene models without previous experimental evidence in both subspecies. Cloning and sequence analysis of the previously unsupported models suggests that the predicted gene structure of nearly half of those models needs improvement. Coupled with comparative gene model mapping, the tiling microarray analysis identified 549 new models for the japonica chromosome, representing an 18% increase in the annotated protein-coding capacity. Furthermore, an asymmetric distribution of genome elements along the chromosome was found that coincides with the cytological definition of the heterochromatin and euchromatin domains. The heterochromatin domain appears to associate with distinct chromosome level transcriptional activities under normal and stress conditions. Conclusion: These results demonstrated the utility of genome tiling microarrays in evaluating annotated rice gene models and in identifying novel transcriptional units. The tiling microarray analysis further revealed a chromosomewide transcription pattern that suggests a role for transposable element-enriched heterochromatin in shaping global transcription in response to environmental changes in rice.

Published
2005
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47. A Pilot Study of Transcription Unit Analysis in Rice Using Oligonucleotide Tiling-path Microarray.

Author

Viktor Stolc, Xiangfeng Wang, and Xueyong Li

Subjects
GENOMES, CELL nuclei, RNA, GENETICS
Abstract

Abstract As the international efforts to sequence the rice genome are completed, an immediate challenge and opportunity is to comprehensively and accurately define all transcription units in the rice genome. Here we describe a strategy of using high-density oligonucleotide tiling-path microarrays to map transcription of the japonica rice genome. In a pilot experiment to test this approach, one array representing the reverse strand of the last 11.2 Mb sequence of chromosome 10 was analyzed in detail based on a mathematical model developed in this study. Analysis of the array data detected 77% of the reference gene models in a mixture of four RNA populations. Moreover, significant transcriptional activities were found in many of the previously annotated intergenic regions. These preliminary results demonstrate the utility of genome tiling microarrays in evaluating annotated rice gene models and in identifying novel transcription units that will facilitate rice genome annotation. [ABSTRACT FROM AUTHOR]

Published
2005

48. GENETIC CONTROL OF BLOOD NEUTROPHIL CONCENTRATION IN THE RAT

Author

Viktor Stolc

Subjects
Genetics, Neutrophils, Offspring, Neutrophile, Immunology, Rats, Inbred Strains, Immunogenetics, Quantitative trait locus, Biology, Phenotype, Rats, Andrology, Leukocyte Count, Backcrossing, Animals, Lymphocytes, Allele, Alleles, Crosses, Genetic, Hybrid
Abstract

SUMMARY Two phenotypes that characterize low and high neutrophil concentrations in blood were found in the rat. It is possible that either two regulating alleles control the high (Nr-1a) and the low (Nr-1b) neutrophil concentration or that a polygenic system affects the neutrophil concentration in blood. The F1 hybrids of four intercrosses had low neutrophil levels in blood that suggested a dominant effect of the Nr-1b allele. The backcross progeny showed abnormal segregation of the neutrophil phenotypes. The high phenotype was expressed in only 5% of the offspring. The presence of the two phenotypes and their distribution in the backcross progeny was confirmed by the computer program SKUMIX that resolved the quantitative traits into two discrete distributions with 95% and 5% representation. Because the logistic of SKUMIX can not rule out the polygenic effect, only further breeding studies using linked markers can resolve the mechanism of the genetic control of neutrophil concentration in the rat.

Published
1988
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49. Genetics of meprin in the rat

Author

Viktor Stolc

Subjects
Genetics, chemistry.chemical_classification, Kidney, Locus (genetics), Biology, Molecular biology, Centimorgan, Enzyme, medicine.anatomical_structure, chemistry, Backcrossing, medicine, High activity, Allele, Gene
Abstract

The locus encoding for meprin activity in kidney was found polymorphic in the rat. The BDIV and COP strains that carried theMep-1a allele had high meprin concentration in the kidney, while the ACI, BN, LE and LEW strains that carried theMep-1b allele had low meprin levels. TheMep-1a allele that controlled the high activity enzyme was expressed in a dominant fashion in the (BN × COP) F1 progeny. The backcross studies showed that the segregation of alleles at theMep-1 and theGlo-1 loci was normal and that the genes were linked (x2 = 4.06,P < 0.05). The map distance between theMep-1 andGlo-1 genes was 41 ± 4 centimorgans.

Published
1986
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50. Restrained Adenyl Cyclase in Human Neutrophils: Stimulation of Cyclic Adenosine 3':5'-Monophosphate Formation and Adenyl Cyclase Activity by Phagocytosis and Prostaglandins

Author

Viktor Stolc

Subjects
medicine.medical_specialty, Chemistry, Phagocytosis, Immunology, Adrenergic, Adenylate kinase, Alpha (ethology), Stimulation, Cell Biology, Hematology, Propranolol, Biochemistry, Cyclase, Endocrinology, Phentolamine, Internal medicine, medicine, medicine.drug
Abstract

We observed that prostuglandins (PG) E1, E2, A1, A2, B1, and F2 alpha increase cAMP concentration in resting neutrophils. In phagocytosing cells, an additional enhancement was seen with PG E1 and PG A2. Such a stimulatory effect of Pg E1 was noted any time during phagocytosis of latex microparticles (3-18 min). Adrenergic inhibitors, phentolamine and propranolol, did not interfere with the stimulatory action of PG E1 on cAMP level in resting and phagocytosing leukocytes. Both aforementioned inhibitors enhanced cAMP level in resting and phagocytosing neutrophils at 1 mM concentration, and an additional increase was seen in PG E1stimulated leukocytes. Although phosphodiesterase activity was unchanged by phagocytosis and PG E1 action, adenylate cyclase (AC) activity was significantly higher in neutrophil homogenates after phagocytosis of latex particles. In contrary, contact of human lymphocytes with latex particles revealed a decrease in AC activity. These data indicate that AC-cAMP system is partly in a restrained state in resting neutrophils and can be relieved by phagocytosis.

Published
1974
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