bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring biological networks in 3D, stereoscopic 3D and immersive 3D with iCAVE
Authors: Kalaycı Selim , Gümüş Zeynep H. 
Published: November 2017

ABSTRACTBiological networks are becoming increasingly large and complex, pushing the limits of existing 2D tools. iCAVE is an open source software tool for interactive visual explorations of large and complex networks in 3D, stereoscopic 3D or immersive 3D. It introduces new 3D network layout algorithms and 3D-extensions of popular 2D network layout, clustering and edge bundling algorithms to assists researchers in understanding the underlying patterns in large, multi-layered, clustered or complex networks. This protocol aims to guide new users on the basic functions of iCAVE for loading data, laying out networks (single or multi-layered), bundling edges, clustering networks, visualizing clusters, visualizing data attributes and saving output images or videos. It also provides examples on visualizing networks constrained in physical 3D space (e.g. proteins; neurons; brain). It is accompanied with a new version of iCAVE with an enhanced user interface and highlights new features useful for existing users.Significance StatementNetwork representations assist in systems-level data exploration in many research fields, providing valuable insights. However, with the recent advances in experimental technologies, biological networks are becoming increasingly large and complex, necessitating new data visualization solutions. We have recently developed iCAVE (Liluashvili et al., 2017), an open?source software platform that enables 3D (optionally stereoscopic and or immersive) visualizations of complex, dense or multi?layered biological networks. Users can select from several new 3D network layout and clustering algorithms, bundle network edges and customize network attributes to reveal hidden structures within them. This protocol guides new users on loading, navigating, customizing and saving networks in iCAVE and is accompanied by an updated version of the software.
Bioinformatics Workflow Management With The Wobidisco Ecosystem
Authors: Mondet Sebastien , Aksoy Bulent Arman , Rozenberg Leonid , Hodes Isaac , Hammerbacher Jeff 
Published: November 2017

ReferencesTo conduct our computational experiments, our team developed a set of workflow-management-related projects: Ketrew, Biokepi, and Coclobas. The family of tools and libraries are designed with reliability and flexibility as main guiding principles. We describe the components of the software stack and explain the choices we made. Every piece of software is free and open-source; the umbrella documentation project is available at https://github.com/hammerlab/wobidisco.
The elephant in the room- Universal coverage for Costly treatments in an upper middle income country
Authors: Kaur RP , Ho GF , Mastura MY , Goh PP , Salowi Mohamad Aziz , Muhd. Radzi AH , Hau Anwar , Sathar Jameela , Robaayah Z , Selladurai Benedict , Suleiman Abu Bakar , Morad Zaki , Ghazali A , Lim TO 
Published: November 2017

AbstractBackgroundUpper middle income countries have made substantial progress towards universal health coverage. We investigated whether the coverage extended to diseases that incur catastrophic health spending, the contribution of pooled financing and the factors driving it in Malaysia.MethodsWe adapted the WHO definition of catastrophic health spending to define costly treatment as one that cost, at prevailing market price, more than 10% of the median annual household income in Malaysia. Coverage is defined as the proportion of patients in a year who were in need of a treatment and who received it. Data to estimate coverage and financing were extracted from the published and grey literature, as well as secondary data sources available on disease epidemiology and healthcare in Malaysia.ResultsWe found coverage varies from universal for dialysis, cataract surgery, medicines for organ transplant and CML, to practically none for HCV, stroke, psoriasis and epilepsy surgery. Coverage of targeted therapies for solid cancers, knee replacement surgery, anti-TNF for arthritis and coagulation factors for haemophilia were poor while iron chelation for thalassemia, coronary revacularization, epoetin and anti-retrovirals were barely adequate. Coverage correlates negatively (r=-0.82) with health benefits foregone, and is entirely driven by the contribution of pooled financing (r=0.99 p<0.0001). The relative effectiveness of a treatment, its budget impact, media coverage and political influence of the disease area have little influence on financing. Only effectiveness of the leadership representing the therapy area is influential; an increase in one point on the leadership effectiveness scale is associated with 30% increase in the contribution of pooled financing.ConclusionCoverage for catastrophically costly treatments is uneven and inequitable in Malaysia, despite most of these are affordable. Decisions on coverage are driven by political-economic consideration.
Effects of single cage housing on stress, cognitive and seizure parameters in the rat and mouse pilocarpine models of epilepsy
Authors: Manouze H , Ghestem A , Poillerat V , Bennis M , Ba-M’hamed S , Benoliel JJ , Becker C , Bernard C 
Published: November 2017

ABSTRACTMany experimental approaches require housing rodents in individual cages, including in epilepsy research. However, rats and mice are social animals; and individual housing constitutes a stressful situation. The goal of the present study was to determine the effects of individual housing as compared to conditions maintaining social contact on stress markers and epilepsy. Control male mice socially housed during pretest and then transferred to individual cages for six weeks displayed anhedonia, increased anxiety and biological markers of stress as compared to pretest values or mice kept socially housed during six weeks. Pilocarpine-treated mice housed together showed increased levels of anhedonia, anxiety and stress markers as well as decreased cognitive performance as compared to the control group. The differences were more significant in pilocarpine-treated mice housed individually. Anxiety correlated linearly with cognitive performance and stress markers independently of the experimental conditions. In the male rat pilocarpine model, seizures were sixteen times more frequent in singly housed animals as compared to animals kept in pairs. Daily interactions with an experimenter in otherwise singly housed animals was sufficient to produce results identical to those found in animals kept in pairs. We propose that social isolation produces a severe phenotype in terms of stress and seizure frequency as compared to animals maintaining social contact (at least in these two models), a factor that needs to be taken into account for data interpretation, in particular for preclinical studies.Significance StatementMany experimental approaches require housing rodents in individual cages, a stressful condition for social animals, even in an enriched environment context. Using the pilocarpine model of epilepsy in rats and mice, we report that singly housing animals develop a more severe phenotype in terms of stress and epilepsy as compared to animals maintaining social contact. We propose that social isolation adds a degree of complexity for the interpretation of data, which may be particularly relevant for preclinical studies.
Improving microbial electrosynthesis of polyhydroxybutyrate (PHB) from CO2byRhodopseudomonas palustrisTIE-1 using an immobilized iron complex modified cathode
Authors: Rengasamy Karthikeyan , Ranaivoarisoa Tahina Onina , Singh Rajesh , Bose Arpita 
Published: November 2017

AbstractMicrobial electrosynthesis (MES) is a promising bioelectrochemical approach to produce biochemicals. A previous study showed thatRhodopseudomonas palustrisTIE-1 can directly use poised electrodes as electron donors for photoautotrophic growth at cathodic potentials that avoid electrolytic H2production (photoelectroautotrophy). To make TIE-1 an effective biocatalyst for MES, we need to improve its electron uptake ability and growth under photoelectroautotrophic conditions. Because TIE-1 interacts with various forms of iron while using it as a source of electrons for photoautotrophy (photoferrotrophy), we tested the ability of iron-based redox mediators to enhance direct electron uptake. Our data show that soluble iron cannot act as a redox mediator for electron uptake by TIE-1 from a cathode poised at +100mV vs. Standard Hydrogen electrode. We then tested whether an immobilized iron-based redox mediator Prussian Blue (PB) can enhance electron uptake by TIE-1. Chronoamperometry indicates that cathodic current uptake by TIE-1 increased from 1.47 ± 0.04 to 5.6 ± 0.09 µA/cm2(3.8 times) and the production of the bioplastic, polyhydroxybutyrate (PHB) improved from 13.5 ± 0.2 g/L to 18.8 ± 0.5 g/L (1.4 times) on electrodes coated with PB. Overall, our data show that immobilized PB can increase direct electron uptake by TIE-1 and enhances PHB production.
Population Differentiation at theHLAGenes
Authors: Brandt Débora Y. C. , César Jônatas , Goudet Jérôme , Meyer Diogo 
Published: November 2017

ABSTRACTBalancing selection is defined as a class of selective regimes that maintain polymorphism above what is expected under neutrality. Theory predicts that balancing selection reduces population differentiation, as measured by FST. However, balancing selection regimes in which different sets of alleles are maintained in different populations could increase population differentiation. To tackle this issue, we investigated population differentiation at the HLA genes, which constitute the most striking example of balancing selection in humans. We found that population differentiation of single nucleotide polymorphisms (SNPs) at the HLA genes is on average lower than that of SNPs in other genomic regions. However, this result depends on accounting for the differences in allele frequency between selected and putatively neutral sites. Our finding of reduced differentiation at SNPs within HLA genes suggests a predominant role of shared selective pressures among populations at a global scale. However, in pairs of closely related populations, where genome-wide differentiation is low, differentiation at HLA is higher than in other genomic regions. This pattern was reproduced in simulations of overdominant selection. We conclude that population differentiation at the HLA genes is generally lower than genome-wide, but it may be higher for recently diverged population pairs, and that this pattern can be explained by a simple overdominance regime.
Modeling Spatial Genomic Interactions with the Hawkes model
Authors: Bonnet Anna , Rivoirard Vincent , Picard Franck 
Published: November 2017

AbstractThe spatial localization of many DNA-protein interactions is now available thanks to the development of ChIP-Seq, and their investigation calls for adapted statistical methods. Many methods were developped for peak calling, but few were proposed for the downstream analysis of peak-like data, whereas the spatial structure of such data may contain relevant biological information, like binding constraints for instance. Associations between the occurrences of two genomic features are usually assessed by overlaps, but here we propose a statistical model to precisely quantify the spatial interactions between the location of binding events. Our methodology relies on a multivariate spatial process, the Hawkes model, that can also be interpreted in terms of a graphical model to highlightspatial dependencies between genomic features. Using our method, we explore the chromatin landscape of replication origins, and we highlight attractive and repulsive patterns that can be related to the regulation of the spatial program of replication. We compete our method with both pairwise and multivariate approaches, implemented in the packages GenometriCorr and ppstat respectively. We show that our procedure describes with more details the complex patterns of spatial interactions and also provides estimates that are very convenient for interpretation.
Transcriptional Changes of DNA Replication and Repair Factors Over Uveal Melanoma Subtypes
Authors: Kucherlapati Melanie 
Published: November 2017

AbstractBackgroundUncontrolled replication is a process common to all cancers facilitated by the summation of changes accumulated as tumors progress. The aim of this study was to examine small groups of genes with known biology in replication and repair at the transcriptional and genomic levels, correlating alterations with survival in Uveal Melanoma tumor progression. Selected components of Pre-Replication, Pre-Initiation, and Replisome Complexes, DNA Damage Response and Mismatch Repair have been observed.MethodsWe have generated two groups for each gene examined above and below the average alteration level, and compared relative expression and survival across TCGA UVM subtypes based on somatic copy number alteration supported by DNA methylation and mRNA/miRNA/lncRNA expression. Significance between subtypes monosomic or disomic for chromosome 3 was determined by Fisher’s exact test. Kaplan Meier survival distribution based on disease specific survival was compared by log-rank test.ResultsSpecific genes with significant alteration include MCM2 MCM4 and MCM5 of the Minichromosome Maintenance helicase complex, CDC45, MCM10, CIZ1, PCNA, FEN1, LIG1, POLD1, POLE, HUS1, CHECK1, ATRIP, MLH3, and MSH6. We found evidence of Exon 4 skipping in CIZ1 previously identified as a cancer variant and reportedly used as an early serum biomarker in lung cancer, accompanied by evidence of instability of a mononucleotide repeat in Intron 3. Mismatch Repair protein MLH3 was found to have splicing variations with deletions to both Exon 5 and Exon 7 simultaneously. PCNA, FEN1, and LIG1 had increased relative expression levels not due to their mutation or to copy number variation.ConclusionWe have observed differences in relative and differential expression that support the concept that selected replication and repair genes and their products are causally involved in the origin and progression of uveal melanoma, suggesting specific avenues for early biomarker identification and also therapeutic approach.
Toward a Genome Scale Sequence Specific Dynamic Model of Cell-Free Protein Synthesis inEscherichia coli
Authors: Horvath Nicholas , Vilkhovoy Michael , Wayman Joseph A. , Calhoun Kara , Swartz James , Varner Jeffrey D. 
Published: November 2017

AbstractCell-free protein expression systems have become widely used in systems and synthetic biology. In this study, we developed an ensemble of dynamicE. colicell-free protein synthesis (CFPS) models. Model parameters were estimated from a training dataset for the cell-free production of a protein product, chloramphenicol acetyltransferase (CAT). The dataset consisted of measurements of glucose, organic acids, energy species, amino acids, and CAT. The ensemble accurately predicted these measurements, especially those of the central carbon metabolism. We then used the trained model to evaluate the optimality of protein production. CAT was produced with an energy efficiency of 12%, suggesting that the process could be further optimized. Reaction group knockouts showed that protein productivity and the metabolism as a whole depend most on oxidative phosphorylation and glycolysis and gluco-neogenesis. Amino acid biosynthesis is also important for productivity, while the overflow metabolism and TCA cycle affect the overall system state. In addition, the translation rate is shown to be more important to productivity than the transcription rate. Finally, CAT production was robust to allosteric control, as was most of the network, with the exception of the organic acids in central carbon metabolism. This study is the first to use kinetic modeling to predict dynamic protein production in a cell-freeE. colisystem, and should provide a foundation for genome scale, dynamic modeling of cell-freeE. coliprotein synthesis.
JQ1 affects BRD2-dependent and independent transcription regulation without disrupting H4-hyperacetylated chromatin states
Authors: Handoko Lusy , Kaczkowski Bogumil , Hon Chung-Chau , Lizio Marina , Wakamori Masatoshi , Matsuda Takayoshi , Ito Takuhiro , Jeyamohan Prashanti , Sato Yuko , Sakamoto Kensaku , Yokoyama Shigeyuki , Kimura Hiroshi , Minoda Aki , Umehara Takashi 
Published: November 2017

ABSTRACTThe bromodomain and extra-terminal domain (BET) proteins are promising drug targets for cancer and immune diseases. However, BET inhibition effects have been studied more in the context of bromodomain-containing protein 4 (BRD4) than BRD2, and the BET protein association to histone H4-hyperacetylated chromatin is not understood at the genome-wide level. Here, we report transcription start site (TSS)-resolution integrative analyses of ChIP-seq and transcriptome profiles in human non-small cell lung cancer (NSCLC) cell line H23. We show that di-acetylation at K5 and K8 of histone H4 (H4K5acK8ac) co-localizes with H3K27ac and BRD2 in the majority of active enhancers and promoters, where BRD2 has a stronger association with H4K5acK8ac than H3K27ac. Interestingly, although BET inhibition by JQ1 led to complete reduction of BRD2 binding to chromatin, only local changes of H4K5acK8ac levels were observed. In addition, a remarkable number of BRD2-bound genes, including MYC and its downstream target genes, were transcriptionally upregulated upon JQ1 treatment. Using BRD2-enriched sites and transcriptional activity analysis, we identified candidate transcription factors potentially involved in the JQ1 response in BRD2-dependent and independent manner.
Resolving outbreak dynamics using Approximate Bayesian Computation for stochastic birth-death models
Authors: Lintusaari Jarno , Blomstedt Paul , Sivula Tuomas , Gutmann Michael U. , Kaski Samuel , Corander Jukka 
Published: November 2017

AbstractEarlier research has suggested that Approximate Bayesian Computation (ABC) makes it possible to fit simulator-based intractable birth-death models to investigate communicable disease outbreak dynamics with accuracy comparable to that of exact Bayesian methods. However, recent findings have indicated that key parameters such as the reproductive number R may remain poorly identifiable. Here we show that the identifiability issue can be resolved by taking into account disease-specific characteristics of the transmission process in closer detail. Using tuberculosis (TB) in the San Francisco Bay area as a case-study, we consider the situation where the genotype data are generated as a mixture of three stochastic processes, each with their distinct dynamics and clear epidemiological interpretation.The ABC inference yields stable and accurate posterior inferences about outbreak dynamics from aggregated annual case data with genotype information. We also show that under the proposed model, the infectious population size can be reliably inferred from the data. The estimate is approximately two orders of magnitude smaller compared to assumptions made in the earlier ABC studies, and is much better aligned with epidemiological knowledge about active TB prevalence. Similarly, the reproductive number R related to the primary underlying transmission process is estimated to be nearly three-fold compared with the previous estimates, which has a substantial impact on the interpretation of the fitted outbreak model.
Transcriptional Profiling of Somatostatin Interneurons in the Spinal Dorsal Horn
Authors: Chamessian Alexander , Young Michael , Qadri Yawar , Berta Temugin , Ji Ru-Rong , Van De Ven Thomas 
Published: November 2017

AbstractThe spinal dorsal horn (SDH) is comprised of distinct neuronal populations that process different somatosensory modalities. Somatostatin (SST)-expressing interneurons in the SDH have been implicated specifically in mediating mechanical pain. Identifying the transcriptomic profile of SST neurons could elucidate the unique genetic features of this population and enable selective analgesic targeting. To that end, we combined the Isolation of Nuclei Tagged in Specific Cell Types (INTACT) method and Fluorescence Activated Nuclei Sorting (FANS) to capture tagged SST nuclei in the SDH of adult male mice. Using RNA-sequencing (RNA-seq), we uncovered more than 13,000 genes. Differential gene expression analysis revealed more than 900 genes with at least 2-fold enrichment. In addition to many known dorsal horn genes, we identified and validated several novel transcripts from pharmacologically tractable functional classes: Carbonic Anhydrase 12 (Car12), Phosphodiesterase 11A (Pde11a), Protease-Activated Receptor 3 (F2rl2) and G-protein Coupled Receptor 26 (Gpr26). In situ hybridization of these novel genes revealed differential expression patterns in the SDH, demonstrating the presence of transcriptionally distinct subpopulations within the SST population. Pathway analysis revealed several enriched signaling pathways including cyclic AMP-mediated signaling, Nitric Oxide Synthase signaling, and voltage-gated calcium channels, highlighting the importance of these pathways to SST neuron function. Overall, our findings provide new insights into the gene repertoire of SST dorsal horn neurons and reveal several candidate targets for pharmacological modulation of this pain-mediating population.Significance StatementSomatostatin(SST)-expressing interneurons in the spinal dorsal horn (SDH) are required for the perception of mechanical pain. Identifying the distinctive genes expressed by SST neurons could facilitate the development of novel, circuit-targeting analgesics. Thus, we applied cell type-specific RNA-sequencing (RNA-seq) to provide the first transcriptional profile of SST neurons in the SDH. Bioinformatic analysis revealed hundreds of genes enriched in SST neurons, including several previously undescribed genes from druggable classes (Car12, Pde11a, F2rl2 and Gpr26). Taken together, our study unveils a comprehensive transcriptional signature for SST neurons, highlights promising candidate genes for future analgesic development, and establishes a flexible method for transcriptional profiling of any spinal cord cell type.
Identification of stable reference genes for quantitative PCR in koalas
Authors: Sarker N. , Fabijan J. , Emes R.D. , Hemmatzadeh F. , Meers J. , Moreton J. , Owen H. , Seddon J. M. , Simmons G. , Speight N. , Trott D. , Woolford L. , Tarlinton R.E 
Published: November 2017

ABSTRACTTo better understand host and immune response to diseases, gene expression studies require identification of reference genes with stable expression for accurate normalisation. This study describes the selection and testing of reference genes with stable expression profiles in koala lymph node tissues across two genetically distinct koala populations. From the 25 most stable genes identified in transcriptome analysis, 11 genes were selected for verification using reverse transcription quantitative PCR, in addition to the commonly usedACTBandGAPDHgenes. The expression data were analysed using stable genes statistical software - geNorm, BestKeeper, NormFinder, the comparative ΔCt method and RefFinder. All 13 genes showed relative stability in expression in koala lymph node tissues, howeverTmem97andHmg20awere identified as the most stable genes across the two koala populations.