bluuebunny/crossref_metadata_2025_split huggingface dataset:
PhenoMeNal: Processing and analysis of Metabolomics data in the Cloud
Authors: Peters Kristian , Bradbury James , Bergmann Sven , Capuccini Marco , Cascante Marta , de Atauri Pedro , Ebbels Timothy M D , Foguet Carles , Glen Robert , Gonzalez-Beltran Alejandra , Guenther Ulrich , Handakas Evangelos , Hankemeier Thomas , Haug Kenneth , Herman Stephanie , Holub Petr , Izzo Massimiliano , Jacob Daniel , Johnson David , Jourdan Fabien , Kale Namrata , Karaman Ibrahim , Khalili Bita , Khonsari Payam Emami , Kultima Kim , Lampa Samuel , Larsson Anders , Ludwig Christian , Moreno Pablo , Neumann Steffen , Novella Jon Ander , O’Donovan Claire , Pearce Jake TM , Peluso Alina , Pireddu Luca , Piras Marco Enrico , Reed Michelle AC , Rocca-Serra Philippe , Roger Pierrick , Rosato Antonio , Rueedi Rico , Ruttkies Christoph , Sadawi Noureddin , Salek Reza M , Sansone Susanna-Assunta , Selivanov Vitaly , Spjuth Ola , Schober Daniel , Thévenot Etienne A. , Tomasoni Mattia , van Rijswijk Merlijn , van Vliet Michael , Viant Mark R , Weber Ralf J. M. , Zanetti Gianluigi , Steinbeck Christoph 
Published: September 2018

AbstractBackgroundMetabolomics is the comprehensive study of a multitude of small molecules to gain insight into an organism’s metabolism. The research field is dynamic and expanding with applications across biomedical, biotechnological and many other applied biological domains. Its computationally-intensive nature has driven requirements for open data formats, data repositories and data analysis tools. However, the rapid progress has resulted in a mosaic of independent – and sometimes incompatible – analysis methods that are difficult to connect into a useful and complete data analysis solution.FindingsThe PhenoMeNal (Phenome and Metabolome aNalysis) e-infrastructure provides a complete, workflow-oriented, interoperable metabolomics data analysis solution for a modern infrastructure-as-a-service (IaaS) cloud platform. PhenoMeNal seamlessly integrates a wide array of existing open source tools which are tested and packaged as Docker containers through the project’s continuous integration process and deployed based on a kubernetes orchestration framework. It also provides a number of standardized, automated and published analysis workflows in the user interfaces Galaxy, Jupyter, Luigi and Pachyderm.ConclusionsPhenoMeNal constitutes a keystone solution in cloud infrastructures available for metabolomics. It provides scientists with a ready-to-use, workflow-driven, reproducible and shareable data analysis platform harmonizing the software installation and configuration through user-friendly web interfaces. The deployed cloud environments can be dynamically scaled to enable large-scale analyses which are interfaced through standard data formats, versioned, and have been tested for reproducibility and interoperability. The flexible implementation of PhenoMeNal allows easy adaptation of the infrastructure to other application areas and ‘omics research domains.
Estimation of realized rates of genetic gain and indicators for breeding program assessment
Authors: Rutkoski J.E. 
Published: September 2018

AbstractRoutine estimation of the rate of genetic gain (ΔGt) realized by a breeding program has been proposed as a means to monitor its effectiveness. Several methods of realizedΔGtestimation have been utilized in other studies, but none have been objectively evaluated in a plant breeding context. Stochastic simulations of 80 rice (Oryza sativa) breeding programs over 28 years were done to generate data used to evaluate five methods of realizedΔGtestimation in terms of error, precision, efficiency and correlation between true and predicted annual mean breeding values. Two indicators ofΔGt, the expectedΔGtand the average number of equivalent complete generations (EqCg), were described and evaluated. At best, estimates of realizedΔGtwere over or underestimated by 15% and 27% when considering all 28 years and the past 15 years of breeding respectively. The best methods were the control population, estimated breeding value, and ERA trial methods. Among these, correlations between true and estimatedΔGtwere at best 0.59, indicating that these methods cannot very accurately rank breeding programs in terms of realizedΔGt. The expectedΔGtand the average EqCg were shown to be useful indicators for determining if a non-zero genetic gain is expected. Determining which of the three best realizedΔGtestimation methods evaluated, if any, would be appropriate for any given breeding program should be done with careful consideration of the objectives, resources, seed stocks, and structure of the data available.
A SKI subcomplex specifically required for the degradation of ribosome-free RNA regions
Authors: Zhang Elodie , Khanna Varun , Namane Abdelkader , Doyen Antonia , Dacheux Estelle , Turcotte Bernard , Jacquier Alain , Fromont-Racine Micheline 
Published: September 2018

SummaryThe Ski2-Ski3-Ski8 (SKI) complex assists the RNA exosome during the 3’-5’ degradation of cytoplasmic transcripts. Previous reports showed that the SKI complex is involved in the 3’-5’ degradation of mRNA, including 3’ untranslated regions (UTRs), devoid of ribosomes. Paradoxically, we recently showed that the SKI complex directly interacts with ribosomes during the co-translational mRNA decay and that this interaction is necessary for its RNA degradation promoting activity. Here, we characterized a new SKI-associated factor, Ska1, which antagonizes the SKI-ribosome interaction. We showed that the SKI-Ska1-subcomplex is specifically involved in the degradation of ribosome-free RNA regions such as long mRNA 3’UTRs and cytoplasmic lncRNAs. We propose a model in which the SKI-exosome complex first targets ribosome-free RNA 3’ends in its Ska1-associated form. When the complex reaches the mRNA coding sequence, the Ska1-SKI-exosome complex is exchanged for the SKI-exosome, which interacts directly with ribosomes in order to resume the degradation process.
Behavioral Analysis of Substrate Texture Preference in a Leech,Helobdella austinensis
Authors: Kim Rachel C. , Le Dylan , Ma Kenny , Heath-Heckman Elizabeth A. C. , Whitehorn Nathan , Kristan William B. , Weisblat David A. 
Published: September 2018

ABSTRACTLeeches in the wild are often found on smooth surfaces, such as vegetation, smooth rocks or human artifacts such as bottles and cans, thus exhibiting what appears to be a “substrate texture preference behavior”. Here, we have reproduced this behavior under controlled circumstances, by allowing leeches to step about freely on a range of silicon carbide sandpaper substrates. To begin to understand the neural mechanisms underlying this texture preference behavior, we have determined relevant parameters of leech behavior both on uniform substrates of varying textures, and in a behavior choice paradigm in which the leech is confronted with a choice between rougher and smoother substrate textures at each step. We tested two non-exclusive mechanisms which could produce substrate texture preference: 1) a Diffusion Trap mechanism, in which a leech is more likely to stop moving on a smooth surface than on a rough one, and; 2) an Anterior Choice mechanism, in which a leech is more likely to attach its front sucker (prerequisite for taking a step) to a smooth surface than to a rough one. We propose that both mechanisms contribute to the texture preference exhibited by leeches.
Monitoring the eradication of the highly invasive topmouth gudgeon (Pseudorasbora parva) using a novel eDNA assay
Authors: Robinson Chloe Victoria , de Leaniz Carlos Garcia , Rolla Matteo , Consuegra Sofia 
Published: September 2018

AbstractAquatic Invasive Species (AIS) represent an important threat for Biodiversity and are one of the factors determining the ecological integrity of water bodies under the Water Framework Directive. Eradication is one of the most effective tools for the management of invasive species but has important economic and ecological trade-offs and its success needs to be carefully monitored. We assessed the eradication success of the topmouth gudgeon (Pseudorasbora parva), an invasive fish that poses significant risks to endemic aquatic fauna, in four ponds previously treated with the piscicide Rotenone using a novel environmental DNA (eDNA)-qPCR assay. Topmouth gudgeon was detected in all four treated ponds using 750 mL water samples and in three of the ponds using 15 mL samples, despite the eradication treatment. The highly sensitive qPCR assay detected topmouth gudgeon in a significantly greater proportion of sites (77.5%) than eDNA detection methods based on conventional PCR (35%). Our results highlight the difficulties of eradicating invasive fish and the need to incorporate reliable monitoring methods as part of a risk management strategy under the Water Framework Directive.
Improved inference of chromosome conformation from images of labeled loci
Authors: Ross Brian C. , Costello James 
Published: September 2018

AbstractWe previously published a method that infers chromosome conformation from images of fluorescently-tagged genomic loci, for the case when there are many loci labeled with each distinguishable color. Here we build on our previous work and improve the reconstruction algorithm to address previous limitations. We show that these improvements 1) increase the reconstruction accuracy and 2) allow the method to be used on large-scale problems involving several hundred labeled loci. Simulations indicate that full-chromosome reconstructions at 1/2 Mb resolution are possible using existing labeling and imaging technologies. The updated reconstruction code and the script files used for this paper are available at: https://github.com/heltilda/align3d.
Maternal Circulating MiRNAs That Predict Infant FASD Outcomes Influence Placental Maturation
Authors: Tseng Alexander M. , Mahnke Amanda H. , Wells Alan B. , Salem Nihal A. , Allan Andrea M. , Roberts Victoria H.J. , Newman Natali , Walter Nicole A.R. , Kroenke Christopher D. , Grant Kathleen A. , Akison Lisa K. , Moritz Karen M. , Chambers Christina D. , Miranda Rajesh C. ,   CIFASD
Published: September 2018

AbstractPrenatal Alcohol exposure (PAE), like other pregnancy complications, can result in placental insufficiency and fetal growth restriction, though the linking causal mechanisms are unclear. We previously identified 11 gestationally-elevated maternal circulating miRNAs that predicted infant growth deficits following PAE. Here, we investigated whether theseHEamiRNAs contribute to the pathology of PAE, by inhibiting trophoblast epithelial-mesenchymal transition (EMT), a pathway critical for placental development. We now report for the first time, that PAE inhibits expression of placental pro-EMT pathway members in both rodents and primates, and thatHEamiRNAs collectively, but not individually, mediate placental EMT inhibition.HEamiRNAs collectively, but not individually, also inhibited cell proliferation and the EMT pathway in cultured trophoblasts, while inducing cell stress, and following trophoblast syncytialization, aberrant endocrine maturation. Moreover, a single intra-vascular administration of the pooled murine-expressedHEamiRNAs, to pregnant mice, decreased placental and fetal growth and inhibited expression of pro-EMT transcripts in placenta. Our data suggests thatHEamiRNAs collectively interfere with placental development, contributing to the pathology of PAE, and perhaps also, to other causes of fetal growth restriction.SummaryMaternal gestational circulating microRNAs, predictive of adverse infant outcomes including growth deficits, following prenatal alcohol exposure, contribute to placental pathology by impairing the EMT pathway in trophoblasts.
Bacteria-mediated stabilization of a panel of Picornaviruses
Authors: Aguilera Elizabeth R. , Nguyen Y , Sasaki Jun , Pfeiffer Julie K. 
Published: September 2018

ABSTRACTSeveral viruses encounter various bacterial species within the host and in the environment. Despite these close encounters, the effects of bacteria on picornaviruses specifically is not completely understood. Previous work determined that poliovirus (PV), an enteric virus, has enhanced virion stability when exposed to bacteria or bacterial surface polysaccharides such as lipopolysaccharide. Virion stabilization by bacteria may be important for inter-host transmission since a mutant PV with reduced bacterial binding had a fecal-oral transmission defect in mice. Therefore, we investigated whether bacteria broadly enhance stability of picornaviruses from three different genera: Enterovirus (PV and coxsackievirus B3 (CVB3)), Kobuvirus (Aichi virus) and Cardiovirus (Mengo virus). Furthermore, to delineate strain-specific effects, we examined two strains of CVB3 and a PV mutant with enhanced thermal stability. We determined that specific bacterial strains enhance thermal stability of PV and CVB3, while Mengo virus and Aichi virus are stable at high temperatures in the absence of bacteria. Additionally, we determined that bacteria or lipopolysaccharide can stabilize PV, CVB3, Aichi virus, and Mengo virus during exposure to bleach. These effects are likely mediated through direct interactions with bacteria since viruses bound to bacteria in a pull-down assay. Overall, this work reveals shared and distinct effects of bacteria on a panel of picornaviruses.IMPORTANCERecent studies have shown that bacteria promote infection and stabilization of poliovirus particles, but the breadth of these effects on other members of the Picornaviridae family is unknown. Here, we compared the effect of bacteria on four distinct members of the Picornaviridae family. We found that bacteria reduced inactivation of all of the viruses during bleach treatment, but not all viral strains were stabilized by bacteria during heat treatment. Overall, our data provide insight into how bacteria play differential roles on picornavirus stability.
Full-length transcript characterization of SF3B1 mutation in chronic lymphocytic leukemia reveals downregulation of retained introns
Authors: Tang Alison D. , Soulette Cameron M. , Baren Marijke J van , Hart Kevyn , Hrabeta-Robinson Eva , Wu Catherine J. , Brooks Angela N. 
Published: September 2018

AbstractSF3B1 is one of the most frequently mutated genes in chronic lymphocytic leukemia (CLL) and is associated with poor patient prognosis. While alternative splicing patterns caused by mutations in SF3B1 have been identified with short-read RNA sequencing, a critical barrier in understanding the functional consequences of these splicing changes is that we lack the full transcript context in which these changes are occurring. Using nanopore sequencing technology, we have resequenced full-length cDNA from CLL samples with and without the hotspot SF3B1 K700E mutation, and a normal B cell. We have developed a workflow called FLAIR (Full-Length Alternative Isoform analysis of RNA), leveraging the full-length transcript sequencing data that nanopore affords. We report results from nanopore sequencing that are concordant with known SF3B1 biology from short read sequencing as well as altered intron retention events more confidently observed using long reads. Splicing analysis of nanopore reads between the SF3B1WT and SF3B1K700E samples identifies alternative upstream 3’ splice sites associated with SF3B1K700E. We also find downregulation of intron retention events in SF3B1K700E relative to SF3B1WT and no difference between CLL SF3B1MT and B cell, suggesting an aberrant intron retention landscape in CLL samples lacking SF3B1 mutation. With full-length isoforms, we are able to better estimate the abundance of RNA transcripts that are productive and will likely be translated versus those that are unproductive. Validation from short-read data also reveals a strong branch point sequence in these downregulated intron retention events, consistent with previously reported branch points associated with mutated SF3B1. As nanopore sequencing has yet to become a routine tool for characterization of the transcriptome, our work demonstrates the potential utility of nanopore sequencing for cancer and splicing research.
2.8 Å resolution cryo-EM structure of human parechovirus 3 in complex with Fab from a neutralizing antibody
Authors: Domanska Aušra , Flatt Justin W. , Jukonen Joonas J.J. , Geraets James A. , Butcher Sarah J. 
Published: September 2018

AbstractHuman parechovirus 3 (HPeV3) infection is associated with sepsis in neonates characterized by significant immune activation and subsequent tissue damage. Strategies to limit infection have been unsuccessful due to inadequate molecular diagnostic tools for early detection and lack of a vaccine or specific antiviral therapy. Towards the latter, we present a 2.8 Å-resolution structure of HPeV3 in complex with fragments from a neutralizing human monoclonal antibody AT12-015 using cryo-EM and image reconstruction. Modeling revealed that the epitope extends across neighboring asymmetric units with contributions from capsid proteins VP0, VP1, and VP3. Antibody decoration was found to block binding of HPeV3 to cultured cells. Additionally at high-resolution, it was possible to model a stretch of RNA inside the virion and from this identify the key features that drive and stabilize protein-RNA association during assembly.ImportanceHPeV3 is receiving increasing attention as a prevalent cause of sepsis-like symptoms in neonates, which despite the severity of disease, there are no effective treatments available. Structural and molecular insights into virus neutralization are urgently needed, especially as clinical cases are on the rise. Towards this goal, we present the first structure of HPeV3 in complex with fragments from a neutralizing monoclonal antibody. At high-resolution it was possible to precisely define the epitope that when targeted, prevents virions from binding to cells. Such an atomic-level description is useful for understanding host-pathogen interaction, viral pathogenesis mechanisms, and for finding potential cures for infection and disease.
A Novel Method for the Capture-based Purification of Whole Viral Native RNA Genomes
Authors: Tan Cedric Chih Shen , Maurer-Stroh Sebastian , Wan Yue , Sessions October Michael , de Sessions Paola Florez 
Published: September 2018

ABSTRACTCurrent technologies for targeted characterization and manipulation of viral RNA primarily involve amplification or ultracentrifugation with isopycnic gradients of viral particles to decrease host RNA background. The former strategy is non-compatible for characterizing properties innate to RNA strands such as secondary structure, RNA-RNA interactions, and also for nanopore direct RNA sequencing involving the sequencing of native RNA strands. The latter strategy, ultracentrifugation, causes loss in genomic information due to its inability to retrieve unassembled viral RNA. To address this, we developed a novel application of current nucleic acid hybridization technologies for direct characterization of RNA. In particular, we modified a current enrichment protocol to capture whole viral native RNA genomes for downstream RNA assays to circumvent the abovementioned problems. This technique involves hybridization of biotinylated baits at 500 nucleotides (nt) intervals, stringent washes and release of free native RNA strands using DNase I treatment, with a turnaround time of about 6 h 15 min. RT-qPCR was used as the primary proof of concept that capture-based purification indeed removes host background. Subsequently, capture-based purification was applied to direct RNA sequencing as proof of concept that capture-based purification can be coupled with downstream RNA assays. We report that this protocol was able to successfully purify viral RNA by 561-791 fold. We also report that application of this protocol to direct RNA sequencing yielded a reduction in human host RNA background by 1580 fold, a 99.91% recovery of viral genome with at least 15x coverage, and a mean coverage across the genome of 120x. This report is, to the best of our knowledge, the first description of a capture-based purification method for assays that involve direct manipulation or characterisation of native RNA. This report also describes a successful application of capture-based purification as a direct RNA sequencing strategy that addresses certain limitations of current strategies in sequencing RNA viral genomes.
Mi-2/NuRD complex protects stem cell progeny from mitogenic Notch signaling
Authors: Zacharioudaki Eva , Sanjuan Julia Falo , Bray Sarah 
Published: September 2018

AbstractTo progress towards differentiation, the progeny of stem cells need to extinguish expression of stem cell maintenance genes. Failures in these mechanisms that suppress stem cell programmes can lead to supernumerary stem cells and drive tumorigenesis. In Drosophila neural stem cell lineages, excessive Notch signalling results in supernumerary stem cells causing hyperplasia. But the onset of hyperplasia is considerably delayed implying there are mechanisms that resist the mitogenic signal. Monitoring live the expression of an early NSC marker, the Notch target gene E(spl)mγ, revealed that the normal process of NSC fate attenuation is still initiated even in the presence of excess Notch activity so that the re-emergence of stem cell properties occurs only in older progeny. Screening for factors responsible, we found that depletion of Mi-2 and other members of the NuRD ATP remodeling complex dramatically enhanced the Notch-induced hyperplasia. Under these conditions, E(spl)mγ was no longer extinguished in the stem cell progeny, but instead remained at high levels. We propose that Mi-2 is required for decommissioning stem cell enhancers in their progeny, enabling the switch towards a more differentiated fate and rendering them insensitive to mitogenic factors such as Notch.
EMT network-based feature selection improves prognosis prediction in lung adenocarcinoma
Authors: Shao Borong , Bjaanæs Maria M , Åslaug Helland , Schütte Christof , Conrad Tim 
Published: September 2018

AbstractVarious feature selection algorithms have been proposed to identify cancer prognostic biomarkers. In recent years, however, their reproducibility is criticized. The performance of feature selection algorithms is shown to be affected by the datasets, underlying networks and evaluation metrics. One of the causes is the curse of dimensionality, which makes it hard to select the features that generalize well on independent data. Even the integration of biological networks does not mitigate this issue because the networks are large and many of their components are not relevant for the phenotype of interest. With the availability of multi-omics data, integrative approaches are being developed to build more robust predictive models. In this scenario, the higher data dimensions create greater challenges.We proposed a phenotype relevant network-based feature selection (PRNFS) framework and demonstrated its advantages in lung cancer prognosis prediction. We constructed cancer prognosis relevant networks based on epithelial mesenchymal transition (EMT) and integrated them with different types of omics data for feature selection. With less than 2.5% of the total dimensionality, we obtained EMT prognostic signatures that achieved remarkable prediction performance (average AUC values >0.8), very significant sample stratifications, and meaningful biological interpretations. In addition to finding EMT signatures from different omics data levels, we combined these single-omics signatures into multi-omics signatures, which improved sample stratifications significantly. Both single- and multi-omics EMT signatures were tested on independent multi-omics lung cancer datasets and significant sample stratifications were obtained.