bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptome-based prediction of complex traits in maize
Authors: Azodi Christina B. , Pardo Jeremy , VanBuren Robert , de los Campos Gustavo , Shiu Shin-Han 
Published: March 2019

AbstractThe ability to predict traits from genome-wide sequence information (Genomic Prediction, GP), has improved our understanding of the genetic basis of complex traits and transformed breeding practices. Transcriptome data may also be useful for GP. However, it remains unclear how well transcript levels can predict traits, particularly when traits are scored at different development stages. Using maize genetic markers and transcript levels from seedlings to predict mature plant traits, we found transcript and genetic marker models have similar performance. Surprisingly, genetic markers important for predictions were not close to or identified as regulatory variants for important transcripts. Thus, transcript levels are predictive not simply due to genetic variation. Furthermore, genetic marker models identified only one of 14 benchmark flowering time genes, while transcript models identified five. Our findings highlight that transcriptome data is useful for GP and can provide a link between traits and variation that cannot be readily captured at the sequence level.
Cerebral Blood Flow Increases Across Early Childhood
Authors: Paniukov Dmitrii , Lebel R. Marc , Giesbrecht Gerald , Lebel Catherine 
Published: March 2019

AbstractAdequate cerebral blood flow (CBF) is essential to proper brain development and function. Detailed characterization of CBF developmental trajectories will lead to better understanding of the development of cognitive, motor, and sensory functions, as well as behaviour in children. Previous studies have shown CBF increases during infancy and decreases during adolescence; however, the trajectories during childhood, and in particular the timing of peak CBF, remain unclear. Here, we used arterial spin labeling to map age-related changes of CBF across a large longitudinal sample that included 279 scans on 96 participants (46 girls and 50 boys) aged 2-7 years. CBF maps were analyzed using hierarchical linear regression for every voxel inside the grey matter mask, controlling for multiple comparisons. The results revealed a significant positive linear association between CBF and age in distributed brain regions including prefrontal, temporal, parietal, and occipital cortex, and in the cerebellum. There were no differences in developmental trajectories between males and females. Our findings suggest that CBF continues to increase at least until the age of 7 years, likely supporting the ongoing improvements in behaviour, cognition, motor, and sensory functions of the children in early childhood.Highlights*We mapped cerebral blood flow development longitudinally in 96 typically developing children aged 2-7 years*Cerebral blood flow increased over the full age range*No significant differences between males and females were foundConflicting of InterestR.M.L. is an employee of GE.
Generic and context-dependent gene modulations duringHydrawhole body regeneration
Authors: Wenger Yvan , Buzgariu Wanda , Perruchoud Chrystelle , Loichot Gregory , Galliot Brigitte 
Published: March 2019

AbstractThe cnidarianHydrais a classical model of whole-body regeneration. Historically,Hydraapical regeneration has received more attention than its basal counterpart, most studies considering these two regenerative processes independently. We present here a transcriptome-wide comparative analysis of apical and basal regeneration after decapitation and mid-gastric bisection, augmented with a characterization of positional and cell-type expression patterns in non-regenerating animals. The profiles of 25’637Hydratranscripts are available on HydrATLAS (https://hydratlas.unige.ch), a web interface allowing a convenient access to each transcript profile. These data indicate that generic impulse-type modulations occur during the first four hours post-amputation, consistent with a similar integration of injury-related cues on both sides of the amputation plane. Initial divergences in gene regulations are observed in regenerating tips between four and eight hours post-amputation, followed by a dramatic transcriptomic reprogramming between eight and 16 hours when regulations become sustained. As expected, central components of apical patterning,Wnt3andHyBra1, are among the earliest genes up-regulated during apical regeneration. During early basal regeneration, a BMP signaling ligand (BMP5-8c) and a potential BMP inhibitor (NBL1)are up-regulated, suggesting that BMP signaling is involved in the basal organizer, as supported by higher levels of phosphorylated Smad in the basal region and by the LiCl-induced extension ofNBL1expression. By contrast, upon ectopic activation of Wnt/β-catenin signaling,NBL1is no longer expressed, basal differentiation is not maintained and basal regeneration is abolished. A tight cross-talk between Wnt/β-catenin apically and BMP signaling basally appears necessary for maintaining and regeneratingHydraanatomy.
Causal Network Inference from Gene Transcriptional Time Series Response to Glucocorticoids
Authors: Lu Jonathan , Dumitrascu Bianca , McDowell Ian C. , Jo Brian , Barrera Alejandro , Hong Linda K. , Leichter Sarah M. , Reddy Timothy E. , Engelhardt Barbara E. 
Published: March 2019

AbstractGene regulatory network inference is essential to uncover complex relationships among gene pathways and inform downstream experiments, ultimately paving the way for regulatory network re-engineering. Network inference from transcriptional time series data requires accurate, interpretable, and efficient determination of causal relationships among thousands of genes. Here, we develop Bootstrap Elastic net regression from Time Series (BETS), a statistical framework based on Granger causality for the recovery of a directed gene network from transcriptional time series data. BETS uses elastic net regression and stability selection from bootstrapped samples to infer causal relationships among genes. BETS is highly parallelized, enabling efficient analysis of large transcriptional data sets. We show competitive accuracy on a community benchmark, the DREAM4 100-gene network inference challenge, where BETS is one of the fastest among methods of similar performance but additionally infers whether the causal effects are activating or inhibitory. We apply BETS to transcriptional time series data of 2, 768 differentially-expressed genes from A549 cells exposed to glucocorticoids over a period of 12 hours. We identify a network of 2, 768 genes and 31, 945 directed edges (FDR ≤ 0.2). We validate inferred causal network edges using two external data sources: overexpression experiments on the same glucocorticoid system, and genetic variants associated with inferred edges in primary lung tissue in the Genotype-Tissue Expression (GTEx) v6 project. BETS is freely available as an open source software package athttps://github.com/lujonathanh/BETS.
NOD1 mediates non-canonical inflammasome processing of interleukin-18 in epithelial cells toHelicobacter pyloriinfection
Authors: Tran L. S. , Ying L. , D’Costa K. , Wray-McCann G. , Kerr G. , Le L. , Allison C. C. , Ferrand J. , Chaudhry H. , Emery J. , De Paoli A. , Creed S. , Kaparakis-Liaskos M. , Como J. , Dowling J. , Johanesen P. A. , Kufer T. A. , Pedersen J. S. , Mansell A. , Philpott D. J. , Elgass K. , Abud H. E. , Nachbur U. , Croker B. A. , Masters S. L. , Ferrero R. L. 
Published: March 2019

AbstractThe interleukin-1 family members, IL-1β and IL-18, are processed into their biologically active forms by multi-protein complexes, known as inflammasomes. Although the inflammasome pathways that mediate IL-1β processing in myeloid cells have been extensively studied, those involved in IL-18 processing, particularly in non-myeloid cells, are still poorly understood. Here, we have identified the cytosolic sensor NOD1 as a key regulator of IL-18 processing in epithelial cells responding toHelicobacter pyloriinfection. Importantly, NOD1 processing of IL-18 occurs independently of the canonical inflammasome proteins, NLRP3 and ASC. Instead, NOD1 interacts directly with caspase-1 via homotypic binding of caspase-activation recruitment domains. We show that IL-18 is important in maintaining tissue homeostasis and protecting against pre-neoplastic changes due to gastricH. pyloriinfection. These findings reveal an unanticipated role for NOD1 in a new type of inflammasome that regulates epithelial cell production of bioactive IL-18 with tissue protective functions.
A Transcriptome Fingerprinting Assay for Clinical Immune Monitoring
Authors: Altman Matthew C , Baldwin Nicole , Whalen Elizabeth , Al-Shaikhly Taha , Presnell Scott , Khaenam Prasong , Gersuk Vivian H , Chiche Laurent , Jourde-Chiche Noemie , Phillips J Theodore , Klintmalm Goran , O’Garra Anne , Berry Matthew , Bloom Chloe , Wilkinson Robert J , Graham Christine M , Lipman Marc , Lertmemongkolchai Ganjana , Kheradmand Farrah , Mejias Asuncion , Ramilo Octavio , Palucka Karolina , Pascual Virginia , Banchereau Jacques , Chaussabel Damien 
Published: March 2019

ABSTRACTBackgroundWhile our understanding of the role that the immune system plays in health and disease is growing at a rapid pace, available clinical tools to capture this complexity are lagging. We previously described the construction of a third-generation modular transcriptional repertoire derived from genome-wide transcriptional profiling of blood of 985 subjects across 16 diverse immunologic conditions, which comprises 382 distinct modules.ResultsHere we describe the use of this modular repertoire framework for the development of a targeted transcriptome fingerprinting assay (TFA). The first step consisted in down-selection of the number of modules to 32, on the basis of similarities in changes in transcript abundance and functional interpretation. Next down-selection took place at the level of each of the 32 modules, with each one of them being represented by four transcripts in the final 128 gene panel. The assay was implemented on both the Fluidigm high throughput microfluidics PCR platform and the Nanostring platform, with the list of assays target probes being provided for both. Finally, we provide evidence of the versatility of this assay to assess numerous immune functionsin vivoby demonstrating applications in the context of disease activity assessment in systemic lupus erythematosus and longitudinal immune monitoring during pregnancy.ConclusionsThis work demonstrates the utility of data-driven network analysis applied to large-scale transcriptional profiling to identify key markers of immune responses, which can be downscaled to a rapid, inexpensive, and highly versatile assay of global immune function applicable to diverse investigations of immunopathogenesis and biomarker discovery.
The planktonic protist interactome: where do we stand after a century of research?
Authors: Markussen Bjorbækmo Marit F. , Evenstad Andreas , Røsæg Line Lieblein , Krabberød Anders K. , Logares Ramiro 
Published: March 2019

AbstractMicrobial interactions are crucial for Earth ecosystem function, yet our knowledge about them is limited and has so far mainly existed as scattered records. Here, we have surveyed the literature involving planktonic protist interactions and gathered the information in a manually curated Protist Interaction DAtabase (PIDA). In total, we have registered ~2,500 ecological interactions from ~500 publications, spanning the last 150 years. All major protistan lineages were involved in interactions as hosts, symbionts, parasites, predators and/or prey. Symbiosis was the most common interaction (43% of all records), followed by predation (39%) and parasitism (18%). Using bipartite networks, we found that protistan predators seem to be “multivorous”, while parasite-host and symbiont-host interactions appear to have moderate degrees of specialization. The SAR supergroup (i.e. Stramenopiles, Alveolata and Rhizaria) heavily dominated PIDA, and comparisons against a global-ocean molecular survey (TARA Oceans) indicated that several SAR lineages, which are abundant and diverse in the marine realm, were underrepresented among the compiled interactions. All in all, despite historical biases, our work not only unveils large-scale eco-evolutionary trends in the protist interactome, but it also constitutes an expandable resource to investigate protist interactions and to test hypotheses deriving from omics tools.
Revealing virulence potential of clinical and environmental Aspergillus fumigatus isolates using Whole-genome sequencing
Authors: Puértolas-Balint F. , Rossen J.W.A. , Oliveira dos Santos C. , Chlebowicz M.A. , Raangs E. , van Putten M.L. , Sola-Campoy P.J. , Han L. , Schmidt M. , García-Cobos S. 
Published: March 2019

AbstractAspergillus fumigatus is an opportunistic airborne pathogen and one of the most common causative agents of human fungal infections. A restricted number of virulence factors have been described but none of them lead to a differentiation of the virulence level among different strains. In this study, we analyzed the whole-genome sequence of a set of A. fumigatus isolates from clinical and environmental origin to compare their genomes and to determine their virulence profiles. For this purpose, a database containing 244 genes known to be associated with virulence was built. The genes were classified according to their biological function into factors involved in thermotolerance, resistance to immune responses, cell wall structure, toxins and secondary metabolites, allergens, nutrient uptake and signaling and regulation. No difference in virulence profiles was found between clinical isolates causing an infection and a colonizing clinical isolate, nor between isolates from clinical and environmental origin. We observed the presence of genetic repetitive elements located next to virulence related gene groups, which could potentially influence their regulation. In conclusion, our genomic analysis reveals that A. fumigatus, independently of their source of isolation, are potentially pathogenic at the genomic level, which may lead to fatal infections in vulnerable patients. However, other determinants such as genetic variations in virulence related genes and host-pathogen interactions most likely influence A. fumigatus pathogenicity and further studies should be performed.ImportanceAspergillus spp. infections are among the most clinically relevant fungal infections also presenting treatment difficulties due to increasing antifungal resistance. The lack of key virulence factors and a broad genomic diversity complicates the development of targeted diagnosis and novel treatment strategies. A widely spread variability in virulence has been reported for experimental, clinical and environmental isolates. Here we provide supporting evidence that members of this species are fully capable of establishing an infection in immunosuppressed hosts according to their virulence content at the genomic level. Due to the possible clinical complications, studies are urgently required linking strain’s virulent phenotype with the genotype to better understand the virulence activation of this important fungal pathogen.
Yellow Fever Vaccine Protects Resistant and Susceptible Mice Against Zika Virus Infection
Authors: Santos Ana C. Vicente , Guedes-da-Silva Francisca H. , Dumard Carlos H. , Ferreira Vivian N. S. , Costa Igor P. S. da , Machado Ruana A. , Barros-Aragão Fernanda G. Q. , Neris Rômulo L. S. , dos-Santos Júlio S. , Assunção-Miranda Iranaia , Figueiredo Claudia P. , Dias André A. , Gomes Andre M. O. , Matos Guedes Herbert L. de , Oliveira Andrea C. , Silva Jerson L. 
Published: March 2019

AbstractZika virus (ZIKV) emerged as an important infectious disease agent in Brazil in 2016. Infection usually leads to mild symptoms but severe congenital neurological disorders and Guillain-Barré syndrome have been reported following ZIKV exposure. The development of an effective vaccine against Zika virus is a public health priority, encouraging the preclinical and clinical studies of different vaccine strategies. Here, we describe the protective effect of an already licensed attenuated yellow fever vaccine (17DD) on type-I interferon receptor knockout mice (A129) and immunocompetent (BALB/c) mice infected with ZIKV. Yellow fever virus vaccination results in robust protection against ZIKV, with decreased mortality in the A129 mice, a reduction in the cerebral viral load in all mice, and weight loss prevention in the BALB/c mice. Despite the limitation of yellow fever (17DD) vaccine to elicit antibody production and neutralizing activity against ZIKV, we found that YF immunization prevented the development of neurological impairment induced by intracerebral virus inoculation in adult. Although we used two vaccine doses in our protocol, a single dose was protective, reducing the cerebral viral load. Different Zika virus vaccine models have been tested; however, our work shows that an efficient and certified vaccine, available for use for several decades, effectively protects mice against Zika virus infection. These findings open the possibility for using an available and inexpensive vaccine to a large-scale immunization in the event of a Zika virus outbreak.
Comparative genomics guides elucidation of vitamin B12 biosynthesis in novel human associatedAkkermansia
Authors: Kirmiz Nina , Galindo Kadir , Cross Karissa L. , Luna Estefani , Rhoades Nicholas , Podar Mircea , Flores Gilberto E. 
Published: March 2019

ABSTRACTBackgroundAkkermansia muciniphilais a mucin-degrading bacterium found in the gut of most healthy humans and is considered a ‘next-generation probiotic.’ However, knowledge of the genomic and physiological diversity of human associatedAkkermansiais limited, as only one species has been formally described.ResultsTo begin to fill this knowledge gap, we reconstructed 35 high-quality metagenome assembled genomes from children and combined them with 40 other publicly available genomes from adults and mice for comparative genomic analysis. We identified at least four species-level phylogroups (AmI-AmIV) with distinct functional potentials. Most notably, we identified the presence of putative cobalamin (vitamin B12) biosynthesis genes within the AmII (n=26/28) and AmIII (n=2/2) phylogroups. To test these predictions, 10 novel strains ofAkkermansiawere isolated from adults and screened for essential vitamin B12 biosynthesis genes via PCR. Two strains of the AmII phylogroup were positive for the presence of vitamin B12 biosynthesis genes, while all AmI strains, including the type strainA. muciniphilaMucT, were negative. To demonstrate vitamin B12 biosynthesis, we measured the production of acetate, succinate, and propionate in the presence and absence of vitamin supplementation in representative strains of the AmI and AmII phylogroups since cobalamin is a cofactor in propionate metabolism. Results show that theAkkermansiaAmII strain produced acetate and propionate in the absence of supplementation, which is indicative ofde novovitamin B12 biosynthesis. In contrast, acetate and succinate were the main fermentation products for the AmI strains when vitamin B12 was not supplied in the culture medium.ConclusionsWe identifiedAkkermansiastrains as potentially important vitamin B12 biosynthetic bacteria in the human gut. This novel physiological trait of human associatedAkkermansiamay impact how these bacteria interact with the human host and other members of the human gut microbiome.
Single-step genome-wide association study for resistance toPiscirickettsia salmonisin rainbow trout (Oncorhynchus mykiss)
Authors: Marín-Nahuelpi Rodrigo , Barría Agustín , Cáceres Pablo , López María E. , Bassini Liane N. , Lhorente Jean P. , Yáñez José M. 
Published: March 2019

ABSTRACTOne of the main pathogens affecting rainbow trout (Oncorhynchus mykiss) farming is the facultative intracellular bacteriaPiscirickettsia salmonis. Current treatments, such as antibiotics and vaccines, have not had the expected effectiveness in field conditions. Genetic improvement by means of selection for resistance is proposed as a viable alternative for control. Genomic information can be used to identify the genomic regions associated with resistance and enhance the genetic evaluation methods to speed up the genetic improvement for the trait. The objectives of this study were to i) identify the genomic regions associated with resistance toP. salmonis; and ii) identify candidate genes associated with the trait. We experimentally challenged 2,130 rainbow trout withP. salmonisand genotyped them with a 57 K SNP array. Resistance toP. salmoniswas defined as time to death (TD) and as binary survival (BS). Significant heritabilities were estimated for TD and BS (0.48 ± 0.04 and 0.34 ± 0.04, respectively). A total of 2,047 fish and 26,068 SNPs passed quality control for samples and genotypes. Using a single-step genome wide association analysis (ssGWAS) we identified four genomic regions explaining over 1% of the genetic variance for TD and three for BS. Interestingly, the same genomic region located onOmy27was found to explain the highest proportion of genetic variance for both traits (2.4 and 1.5% for TD and BS, respectively). The identified SNP in this region is located within an exon of a gene related with actin cytoskeletal organization, a protein exploited byP. salmonisduring infection. Other important candidate genes identified are related with innate immune response and oxidative stress. The moderate heritability values estimated in the present study show it is possible to improve resistance toP. salmonisthrough artificial selection in the current rainbow trout population. Furthermore, our results suggest a polygenic genetic architecture and provide novel insights into the candidate genes underpinning resistance toP. salmonisinO. mykiss.
Quantitative Principles ofcis-translational control by general mRNA sequence features in eukaryotes
Authors: Li Jingyi Jessica , Chew Guo-Liang , Biggin Mark D. 
Published: March 2019

ABSTRACTBACKGROUNDGeneral translationalcis-elements are present in the mRNAs of all genes and affect the recruitment, assembly, and progress of preinitiation complexes and the ribosome under many physiological states. These elements are: mRNA folding, upstream open reading frames, specific nucleotides flanking the initiating AUG codon, protein coding sequence length, and codon usage. The quantitative contributions of these sequence features and how and why they coordinate together to control translation rates are not well understood.RESULTSHere we show that these sequence features specify 42%–81% of the variance in translation rates inS.cerevisiae, S.pombe, Arabidopsis thaliana, M.musculus, andH.Sapiens. We establish that control by RNA secondary structure is chiefly mediated by highly folded 25–60 nucleotide segments within mRNA 5’ regions; that changes in tri-nucleotide frequencies between highly and poorly translated 5’ regions are correlated between all species; and that control by distinct biochemical processes is extensively correlated as is regulation by a single process acting in different parts of the same mRNA.CONCLUSIONSOur work shows that the general features control a much larger fraction of the variance in translation rates than previously realized. We provide a more detailed and accurate understanding of the aspects of RNA structure that direct translation in diverse eukaryotes. In addition, we note that the strongly correlated regulation between and withincis-control features will cause more even densities of translational complexes along each mRNA and therefore more efficient use of the translation machinery by the cell.