bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influenza A viruses serially passaged in different MDCK cell lines exhibit limited sequence variation across their genomes, with the exception of the hemagglutinin gene
Authors: Barnard Karen N. , Wasik Brian R. , Alford-Lawrence Brynn K. , Hayward Jessica J. , Weichert Wendy S. , Voorhees Ian E.H. , Holmes Edward C. , Parrish Colin R. 
Published: February 2020

ABSTRACTNew methods for deep sequence analysis provide an opportunity to follow the emergence and dynamics of virus mutations in real time. Although viruses are commonly grown in cell culture for research and for vaccine development, the cells used to grow the virus are often not derived from the same tissue or even the same host that the virus naturally replicates in. The selective pressures of culturing virusin vitroare still only partially understood. MDCK cells are the standard cell for growing influenza viruses yet are derived from the epithelium of the canine kidney and are also heterogenous. We passaged human H3N2, H1N1 pandemic, and canine H3N2 influenza A viruses (IAV) in different lineages of MDCK cells, as well as lines engineered to express variant Sia receptors, including α2,3- and α2,6-linkages orN-glycolylneuraminic acid (Neu5Gc) orN-acetylneuraminic acid (Neu5Ac) forms. MDCK-Type II cells had lower infection efficiency and virus production, and infection appeared more dependent on protease activation of the virus. When viruses were passaged in the different cells, they exhibited only small numbers of consensus-level mutations, and most were within the HA gene. Both human IAVs showed selection for single nucleotide minority variants in the HA stem across cell types, as well as low frequency variants in the HA receptor binding site of virus passaged in cells expressing Neu5Gc. Canine H3N2 also showed minority variants near the receptor-binding site in cells expressing Neu5Gc and also in those expressingα2,6-linkages.IMPORTANCEThe genetic variation and adaptability of viruses are fundamental properties that allow their evolutionary success in the face of differing host environments and immune responses. The growth of viruses in cell culture is widely used for their study and for preparing vaccines. However, the selection pressures that cell passaging imposes on viruses are often poorly understood. We used deep sequence analysis to define, in detail, how three different influenza A viruses respond to passaging in different lineages of canine MDCK cells that are commonly used for their growth, as well as in variant cells engineered to express different forms of their cell surface receptor, sialic acid. This analysis revealed that most mutations occur in the HA gene and few sequence changes in the virus population reached high proportions. This is relevant for understanding the selective pressures of virus growth in cell culture and how it shapes evolutionary patterns.
AutoGeneS: Automatic gene selection using multi-objective optimization for RNA-seq deconvolution
Authors: Aliee Hananeh , Theis Fabian 
Published: February 2020

AbstractTissues are complex systems of interacting cell types. Knowing cell-type proportions in a tissue is very important to identify which cells or cell types are targeted by a disease or perturbation. When measuring such responses using RNA-seq, bulk RNA-seq masks cellular heterogeneity. Hence, several computational methods have been proposed to infer cell-type proportions from bulk RNA samples. Their performance with noisy reference profiles highly depends on the set of genes undergoing deconvolution. These genes are often selected based on prior knowledge or a single-criterion test that might not be useful to dissect closely correlated cell types. In this work, we introduceAutoGeneS, a tool that automatically extracts informative genes and reveals the cellular heterogeneity of bulk RNA samples. AutoGeneS requires no prior knowledge about marker genes and selects genes by simultaneously optimizing multiple criteria: minimizing the correlation and maximizing the distance between cell types. It can be applied to reference profiles from various sources like single-cell experiments or sorted cell populations. Results from human samples of peripheral blood illustrate that AutoGeneS outperforms other methods. Our results also highlight the impact of our approach on analyzing bulk RNA samples with noisy single-cell reference profiles and closely correlated cell types. Ground truth cell proportions analyzed by flow cytometry confirmed the accuracy of the predictions of AutoGeneS in identifying cell-type proportions. AutoGeneS is available for use via a standalone Python package (https://github.com/theislab/AutoGeneS).
In silicocharacterization ofGmSOS1provides a comprehensive understanding for its role in soybean salt tolerance
Authors: Mei Zhi-Chao , Yang Ling-Yan , Liu Zhi-Min , Tang Qi-Li , Hou Xin-Zhao , Xie Li-Jun , Wei Zhu-Jun 
Published: February 2020

AbstractPlantSOS1encodes plasma membrane Na+/H+antiporter, which helps in the exclusion of Na+and improves plant salt tolerance. However, detailed studies ofSOS1in the important oil crop, soybean (Glycine max), are still lacking. In the present study, we carried out a comprehensivein silicoanalysis ofSOS1in soybean. Referring to the analysis of physicochemical properties and structural characteristics, the GmSOS1 is an acidic protein with instability and hydrophobicity. Subcellular localization ofGmSOS1supports the presumption that GmSOS1 is a plasma membrane Na+/H+antiporter. Post-translational modification site prediction indicates 4 amino acids that may be phosphorylated. Further, the protein-protein interaction network and co-functional network signify the potential role ofGmSOS1in salt stress tolerance. Although the interaction betweenGmSOS1andGmHKT1remains elusive, some of the intermediary signaling components of SOS pathway in soybean have been predicted. In addition,in silicoexpression analysis based on transcriptome datasets using publicly available database revealed thatGmSOS1was differentially expressed in tissues and different times. Due to the analysis of its regulation mechanism, we found transcription factors such as WRKY and ERF as well as three miRNAs can regulate the expression ofGmSOS1. Phylogenetic analysis using the homologous amino acid sequence of SOS1s from 26 species was performed to study the conserved motifs among these SOS1 members. Overall, we provide an extensive analysis of theGmSOS1and it promises the primary basis for the study in development and response to salt tolerance.
Next-generation phylogeography resolves post-glacial colonization patterns in a widespread carnivore, the red fox (Vulpes vulpes), in Europe
Authors: McDevitt Allan D. , Coscia Ilaria , Browett Samuel S. , Ruiz-González Aritz , Statham Mark J. , Ruczyńska Inka , Roberts Liam , Stojak Joanna , Frantz Alain C. , Norén Karin , Ågren Erik O. , Learmount Jane , Basto Mafalda , Fernandes Carlos , Stuart Peter , Tosh David G. , Sindicic Magda , Andreanszky Tibor , Isomursu Marja , Panek Marek , Korolev Andrey , Okhlopkov Innokentiy M. , Saveljev Alexander P. , Pokorny Boštjan , Flajšman Katarina , Harrison Stephen W. R. , Lobkov Vladimir , Ćirović Duško , Mullins Jacinta , Pertoldi Cino , Randi Ettore , Sacks Benjamin N. , Kowalczyk Rafał , Wójcik Jan M. 
Published: February 2020

AbstractCarnivores tend to exhibit a lack of (or less pronounced) genetic structure at continental scales in both a geographic and temporal sense and this can confound the identification of post-glacial colonization patterns in this group. In this study we used genome-wide data (using Genotyping-by-Sequencing (GBS)) to reconstruct the phylogeographic history of a widespread carnivore, the red fox (Vulpes vulpes), by investigating broad-scale patterns of genomic variation, differentiation and admixture amongst contemporary populations in Europe. Using 15,003 single nucleotide polymorphisms (SNPs) from 524 individuals allowed us to identify the importance of refugial regions for the red fox in terms of endemism (e.g. Iberia). In addition, we tested multiple post-glacial re-colonization scenarios of previously glaciated regions during the Last Glacial Maximum using an Approximate Bayesian Computation (ABC) approach that were unresolved from previous studies. This allowed us to identify the role of admixture from multiple source population post-Younger Dryas in the case of Scandinavia and ancient land-bridges in the colonization of the British Isles. A natural colonization of Ireland was deemed more likely than an ancient human-mediated introduction as has previously been proposed and potentially points to an increased mammalian fauna on the island in the early post-glacial period. Using genome-wide data has allowed us to tease apart broad-scale patterns of structure and diversity in a widespread carnivore in Europe that was not evident from using more limited marker sets and provides a foundation for next-generation phylogeographic studies in other non-model species.
Microbial association networks give relevant insights into plant pathobiomes
Authors: Pauvert Charlie , Fort Tania , Calonnec Agnès , Faivre d’Arcier Julie , Chancerel Emilie , Massot Marie , Chiquet Julien , Robin Stéphane , Bohan David A. , Vallance Jessica , Vacher Corinne 
Published: February 2020

ABSTRACTInteractions between plant pathogens and other plant-associated microorganisms regulate disease. Deciphering the networks formed by these interactions, termed pathobiomes, is crucial to disease management. Our aim was to investigate whether microbial association networks inferred from metabarcoding data give relevant insights into pathobiomes, by testing whether inferred associations contain signals of ecological interactions. We used Poisson Lognormal Models to construct microbial association networks from metabarcoding data and then investigated whether some of these associations corresponded to interactions measurable in co-cultures or known in the literature, by using grapevine (Vitis vinifera) and the fungal pathogen causing powdery mildew (Erysiphe necator) as a model system. Our model suggested that the pathogen species was associated with 23 other fungal species, forming its putative pathobiome. These associations were not known as interactions in the literature, but one of them was confirmed by our co-culture experiments. The yeastBuckleyzyma aurantiacaimpeded pathogen growth and reproduction, in line with the negative association found in the microbial network. Co-cultures also supported another association involving two yeast species. Together, these findings indicate that microbial networks can provide plausible hypotheses of ecological interactions that could be used to develop microbiome-based strategies for crop protection.
Investigation of microbial community interactions between lake Washington methanotrophs using genome-scale metabolic modeling
Authors: Islam Mohammad Mazharul , Le Tony , Daggumati Shardhat Reddy , Saha Rajib 
Published: February 2020

AbstractBackgroundThe role of methane in global warming has become paramount to the environment and the human society, especially in the past few decades. Methane cycling microbial communities play an important role in the global methane cycle, which is why the characterization of these communities is critical to understand and manipulate their behavior. Methanotrophs are a major player in these communities and are able to oxidize methane as their primary carbon source.ResultsLake Washington is a freshwater lake characterized by a methane-oxygen countergradient that contains a methane cycling microbial community. The major microbial members include methanotrophs such asMethylobacter Tundripaludum 21/22andMethylomonas sp. LW13. In this work, these methanotrophs are studied via developing highly curated genome-scale metabolic models. Each model was then integrated to form a community model with a multi-level optimization framework. The metabolic interactions for the community were also characterized. While both organisms are competitors for methane,Methylobacterwas found to display altruistic behavior in consuming formaldehyde produced byMethylomonasthat inhibits its growth. The community was next tested under carbon, oxygen, and nitrogen limited conditions to observe the systematic shifts in the internal metabolic pathways and extracellular metabolite exchanges. Each condition showed variable differences within the methane oxidation pathway, serine cycle, pyruvate metabolism, and the TCA cycle as well as the excretion of formaldehyde and carbon di-oxide from the community. Finally, the community model was simulated under fixed ratios of these two members to reflect the opposing behavior of the community in synthetic and natural communities. The simulated community demonstrated a noticeable switch in intracellular carbon metabolism and formaldehyde transfer between community members in natural vs. synthetic condition.ConclusionIn this work, we attempted to reveal the response of a simplified methane recycling microbial community from Lake Washington to varying environments and also provide an insight into the difference of dynamics in natural community and synthetic co-cultures. Overall, this study lays the ground forin silicosystems-level studies of freshwater lake ecosystems, which can drive future efforts of understanding, engineering, and modifying these communities for dealing with global warming issues.
Highly reproducible characterization ofEscherichia colitRNA epitranscriptome with a simple method of library preparation for deep sequencing
Authors: Wang Ji , Toffano-Nioche Claire , Lorieux Florence , Gautheret Daniel , Lehmann Jean 
Published: February 2020

ABSTRACTIn conventional RNA high-throughput sequencing, modified bases prevent a large fraction of tRNA transcripts to be converted into cDNA libraries. Recent proposals aiming at resolving this issue take advantage of the interference of base modifications with RT enzymes to detect and identify them by establishing signals from aborted cDNA transcripts. Because some modifications, such as methyl groups, do almost not allow RT bypassing, demethylation and highly processive RT enzymes have been used to overcome these obstacles. Working withEscherichia colias a model system, we show that with a conventional (albeit still engineered) RT enzyme and key optimizations in library preparation, all RT-impairing modifications can be highlighted along the entire tRNA length without a demethylation procedure. This is achieved by combining deep-sequencing samples, which allows to establish aborted transcription signal of higher accuracy and reproducibility, with the potential for differentiating tiny differences in the state of modification of all cellular tRNAs. In addition, our protocol provides estimates of the relative tRNA abundance.
Prevalence of pathogenic variants in DNA damage response genes in patients undergoing cancer risk assessment and reporting a personal history of early-onset renal cancer
Authors: Hartman Tiffiney R. , Demidova Elena V. , Lesh Randy W. , Hoang Lily , Richardson Marcy , Forman Andrea , Kessler Lisa , Speare Virginia , Golemis Erica A. , Hall Michael J. , Daly Mary B. , Arora Sanjeevani 
Published: February 2020

ABSTRACTPurposePathogenic variants (PVs) in a number of genes are known to increase the risk of hereditary renal cancer (hRC). However, many early-onset RC (eoRC) patients undergoing genetic testing lack PVs in hRC genes; thus, their genetic risk remains undefined. To determine if PVs in DNA damage response (DDR) genes are enriched in a convenience sample of eoRC patients undergoing genetic testing.Materials and MethodsRetrospective review of results for 844 unselected eoRC patients, undergoing genetic testing with a multi-gene cancer panel by Ambry Genetics [between July 2012 and December 2016]. The patients were tested with CancerNext and/or CancerNext Expanded panels for a variety of indications. Identified PVs were compared with patient characteristics.ResultsMean age of RC diagnosis was 48 years [range 24-60]. In addition to eoRC, 57.9% patients tested reported at least one additional cancer; breast cancer being the most common (40.1% of females, 2.5% of males). PVs in cancer risk genes were identified in 12.8% of patients—3.7% in RC-specific genes, and 8.55% in DDR genes. DDR gene PVs were most commonly identified inCHEK2, BRCA1/2, andATM. Among the 2.1% of patients with aBRCA1/2PV, <50% reported a personal history of hereditary breast/ovarian-associated cancer. No association between age of RC diagnosis, and prevalence of PVs in RC-specific or DDR genes was observed.ConclusionsMulti-gene panel testing including DDR genes may provide a more comprehensive risk assessment in unselected eoRC patients, and their families. Validation in larger datasets is needed to characterize the association with eoRC.
Polyploidization enhancing genetic recombination of the ancestral diploid genome in the evolution of hexaploid wheat
Authors: Wan Hongshen , Li Jun , Ma Shengwei , Wang Qin , Zhu Xinguo , Liu Zehou , Yang Fan , Yang Manyu , Zheng Jianmin , Li Shizhao , Luo Jiangtao , Yang Wuyun 
Published: February 2020

AbstractAllopolyploidy increases its evolutionary potential by fixing heterosis and the advantage of gene redundancy. Allelic combinations generated from genetic recombination potentially provide many variations to the selection pools for evolution. May there be any relationship between allopolyploidization and genetic recombination? To study the impact of polyploidy on genetic recombination, we selected wheat as a model and simulated its evolution pathway of allopolyploidy by developing synthetic hexaploid wheat. The change of homologous chromosome recombination were investigated on their diploid DD and tetraploid AABB genomes after their allohexaploidization, respectively. The genetic recombination of the ancestral diploid genome ofAegilops tauschiiwas enhanced significantly more than 2 folds after their hexaploidization. Hexaploidization enhancing genetic recombination of the ancestral diploid D genome was firstly reported to be a new way to increase evolutionary potential of wheat, which is beneficial for wheat to conquer their narrow origination of D genome, quickly spread and make it a major crop of the world. Finally, re-synthetizing hexaploid wheat using diverseAe. tauschiispecies with tetraploid wheat can be considered as a pleiotropic strategy to speed adaptive evolution of bread wheat in breeding processes by increasing both gene allele types and genetic recombination variations.
GreenMaps: a Tool for Addressing the Wallacean Shortfall in the Global Distribution of Plants
Authors: Daru Barnabas H. 
Published: February 2020

AbstractThe exponential growth of species occurrence data can facilitate dynamic biodiversity analyses. However, raw biodiversity data alone should not be used indiscriminately due to inherent sampling biases, impediments that contribute to Wallacean shortfall (i.e. the paucity of species’ geographic information). It has been suggested that Wallacean shortfall is a common phenomenon across taxa, however, there is no global assessment geared toward overcoming this impediment for plants, despite the fundamental role of plants in ecosystem stability, food security and biodiversity conservation. Here, I present GreenMaps, a new tool that will permit a rapid initial assessment of the Wallacean shortfall for plants by building base maps of species’ predicted distributions upon which citizen science participation could contribute to spatial
validation of the actual range occupied by species. The initial stages of GreenMaps have now been accomplished, providing a massive dataset of modeled range maps for over 194,000 vascular plant species. This will make it the largest and only global assessment of geographic distributions for plant species at scales relevant to research and conservation. Ultimately, GreenMaps will interface with a mobile application to enable volunteers from any region of the world to validate predicted species distributions to be used for the generation of new and improved global map of plant distributions.
Genome-wide identification and analysis of enhancer regulated microRNAs across 31 human cancers
Authors: Tang Fei , Lang Mei , Wang Wenzhu , Li Yanjing , Li Changying , Tan Zheng tang , Yue Junjie , Guo Zhiyun 
Published: February 2020

AbstractEnhancers are cis-regulatory DNA elements that positively regulate the transcription of target genes in a tissue-specific manner and dysregulation in various diseases such as cancer. Recent studies showed that enhancers can regulate miRNAs and participate in the biological synthesis of miRNAs. However, the network of enhancer-regulated miRNAs across multiple cancers is still unclear. Here, a total of 2,418 proximal enhancer-miRNA interactions and 1,280 distal enhancer-miRNA interactions were identified through the integration of genomic distance, co-expression, and 3D genome data in 31 cancers. The results showed that both proximal and distal interactions exhibited significant tissue-specific feature and there was a noteworthy positive correlation between the expression of miRNA and the number of regulated enhancers in most tissues. Furthermore, it was found that there was a high correlation between the formation of enhancer-miRNA pairs and the expression of eRNAs whether in distal or proximal regulation. The characteristics analysis showed that miRes (enhancers that regulated miRNAs) and non-miRes presented significant differences in sequence conservation, GC content and histone modification signatures. Notably, GC content, H3K4me1, H3K36me3 were present differently between distal regulation and proximal regulation, suggesting they might participate in chromosome looping of enhancer-miRNA interactions. Finally, we introduced a case study, enhancer: chr1:1186391-1186507∼miR-200a was highly relevant to the survival of thyroid cancer patients and a cis-eQTL SNP on enhancer affected the expression TNFRSF18 gene as a tumor suppressor.
Genome wide association study reveals plant loci controlling heritability of the rhizosphere microbiome
Authors: Deng Siwen , Caddell Daniel , Yang Jinliang , Dahlen Lindsay , Washington Lorenzo , Coleman-Derr Devin 
Published: February 2020

AbstractHost genetics has recently been shown to be a driver of plant microbiome composition. However, identifying the underlying genetic loci controlling microbial selection remains challenging. Genome wide association studies (GWAS) represent a potentially powerful, unbiased method to identify microbes sensitive to host genotype, and to connect them with the genetic loci that influence their colonization. Here, we conducted a population-level microbiome analysis of the rhizospheres of 200 sorghum genotypes. Using 16S rRNA amplicon sequencing, we identify rhizosphere-associated bacteria exhibiting heritable associations with plant genotype, and identify significant overlap between these lineages and heritable taxa recently identified in maize. Furthermore, we demonstrate that GWAS can identify host loci that correlate with the abundance of specific subsets of the rhizosphere microbiome. Finally, we demonstrate that these results can be used to predict rhizosphere microbiome structure for an independent panel of sorghum genotypes based solely on knowledge of host genotypic information.