bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-cell RNA-Sequencing uncovers transcriptional states and fate decisions in haematopoiesis
Authors: Athanasiadis Emmanouil I. , Botthof Jan G. , Andres Helena , Ferreira Lauren , Lio Pietro , Cvejic Ana 
Published: March 2017

ABSTRACTThe success of marker-based approaches for dissecting haematopoiesis in mouse and human is reliant on the presence of well-defined cell-surface markers specific for diverse progenitor populations. An inherent problem with this approach is that the presence of specific cell surface markers does not directly reflect the transcriptional state of a cell. Here we used a marker-free approach to computationally reconstruct the blood lineage tree in zebrafish and order cells along their differentiation trajectory, based on their global transcriptional differences. Within the population of transcriptionally similar stem and progenitor cells our analysis revealed considerable cell-to-cell differences in their probability to transition to another, committed state. Once fate decision was executed, the suppression of transcription of ribosomal genes and up-regulation of lineage specific factors coordinately controlled lineage differentiation. Evolutionary analysis further demonstrated that this haematopoietic program was highly conserved between zebrafish and higher vertebrates.
A framework to identify modifier genes in patients with Phelan-McDermid syndrome
Authors: Tabet Anne-Claude , Rolland Thomas , Ducloy Marie , Lévy Jonathan , Buratti Julien , Mathieu Alexandre , Haye Damien , Perrin Laurence , Dupont Céline , Passemard Sandrine , Capri Yline , Verloes Alain , Drunat Séverine , Keren Boris , Mignot Cyril , Marey Isabelle , Jacquette Aurélia , Whalen Sandra , Pipiras Eva , Benzacken Brigitte , Chantot-Bastaraud Sandra , Afenjar Alexandra , Héron Delphine , Le Caignec Cédric , Beneteau Claire , Pichon Olivier , Isidor Bertrand , David Albert , Dupont Jean-Michel , Kemeny Stephan , Gouas Laetitia , Vago Philippe , Mosca-Boidron Anne-Laure , Faivre Laurence , Missirian Chantal , Philip Nicole , Sanlaville Damien , Edery Patrick , Satre Véronique , Coutton Charles , Devillard Françoise , Dieterich Klaus , Vuillaume Marie-Laure , Rooryck Caroline , Lacombe Didier , Pinson Lucile , Gatinois Vincent , Puechberty Jacques , Chiesa Jean , Lespinasse James , Dubourg Christèle , Quelin Chloé , Fradin Mélanie , Journel Hubert , Toutain Annick , Martin Dominique , Benmansour Abdelamdjid , Toro Roberto , Amsellem Frédérique , Delorme Richard , Bourgeron Thomas 
Published: March 2017

ABSTRACTPhelan-McDermid syndrome (PMS) is characterized by a variety of clinical symptoms with heterogeneous degrees of severity, including intellectual disability, speech impairment, and autism spectrum disorders (ASD). It results from a deletion of the 22q13 locus that in most cases includes theSHANK3gene.SHANK3is considered a major gene for PMS, but the factors modulating the severity of the syndrome remain largely unknown. In this study, we investigated 85 PMS patients with different 22q13 rearrangements (78 deletions, 7 duplications). We first explored their clinical features and provide evidence for frequent corpus callosum abnormalities. We then mapped candidate genomic regions at the 22q13 locus associated with risk of clinical features, and suggest a second locus associated with absence of speech. Finally, in some cases, we identified additional rearrangements at loci associated with ASD, potentially modulating the severity of the syndrome. We also report the firstSHANK3deletion transmitted to five affected daughters by a mother without intellectual disability nor ASD, suggesting that some individuals could compensate for such mutations. In summary, we shed light on the genotype-phenotype relationship of PMS, a step towards the identification of compensatory mechanisms for a better prognosis and possibly treatments of patients with neurodevelopmental disorders.
GROOLS: reactive graph reasoning for genome annotation through biological processes
Authors: Mercier Jonathan , Josso Adrien , Médigue Claudine , Vallenet David 
Published: March 2017

AbstractBackgroundHigh quality functional annotation is essential for understanding the phenotypic consequences encoded in a genome. Despite improvements in bioinformatics methods, millions of sequences in databanks are not assigned reliable functions. The curation of protein functions in the context of biological processes is a way to evaluate and improve their annotation.ResultsWe developed an expert system using paraconsistent logic, named GROOLS (Genomic Rule Object-Oriented Logic System), that evaluates the completeness and the consistency of predicted functions through biological processes like metabolic pathways. Using a generic and hierarchical representation of knowledge, biological processes are modeled in a graph from which observations (i.e. predictions and expectations) are propagated by rules. At the end of the reasoning, conclusions are assigned to biological process components and highlight uncertainties and inconsistencies. Results on 14 microbial organisms are presented.ConclusionsGROOLS software is designed to evaluate the overall accuracy of functional unit and pathway predictions according to organism experimental data like growth phenotypes. It assists biocurators in the functional annotation of proteins by focusing on missing or contradictory observations.
Genomic basis and evolutionary potential for extreme drought adaptation inArabidopsis thaliana
Authors: Exposito-Alonso Moises , Vasseur François , Ding Wei , Wang George , Burbano Hernán A. , Weigel Detlef 
Published: March 2017

Because earth is currently experiencing unprecedented climate change, it is important to predict how species will respond to it. However, geographically-explicit predictive studies frequently ignore that species are comprised of genetically diverse individuals that can vary in their degree of adaptation to extreme local environments; properties that will determine the species’ ability to withstand climate change. Because an increase in extreme drought events is expected to challenge plant communities with global warming, we carried out a greenhouse experiment to investigate which genetic variants predict surviving an extreme drought event and how those variants are distributed across EurasianArabidopsis thalianaindividuals. Genetic variants conferring higher drought survival showed signatures of polygenic adaptation, and were more frequently found in Mediterranean and Scandinavian regions. Using geoenvironmental models, we predicted that Central European populations might lag behind in adaptation by the end of the 21stcentury. Further analyses showed that a population decline could nevertheless be compensated by natural selection acting efficiently over standing variation or by migration of adapted individuals from populations at the margins of the species’ distribution. These findings highlight the importance of within-species genetic heterogeneity in facilitating an evolutionary response to a changing climate.One-sentence summary“Future genetic changes inA. thalianapopulations can be forecast by combining climate change models with genomic predictions based on experimental phenotypic data.”
SQANTI: extensive characterization of long read transcript sequences for quality control in full-length transcriptome identification and quantification
Authors: Tardaguila Manuel , Fuente Lorena de la , Marti Cristina , Pereira Cécile , Pardo-Palacios Francisco Jose , Risco Hector del , Ferrell Marc , Mellado Maravillas , Macchietto Marissa , Verheggen Kenneth , Edelmann Mariola , Ezkurdia Iakes , Vazquez Jesus , Tress Michael , Mortazavi Ali , Martens Lennart , Rodriguez-Navarro Susana , Moreno Victoria , Conesa Ana 
Published: March 2017

ABSTRACTHigh-throughput sequencing of full-length transcripts using long reads has paved the way for the discovery of thousands of novel transcripts, even in very well annotated organisms as mice and humans. Nonetheless, there is a need for studies and tools that characterize these novel isoforms. Here we present SQANTI, an automated pipeline for the classification of long-read transcripts that computes 47 descriptors that can be used to assess the quality of the data and of the preprocessing pipelines. We applied SQANTI to a neuronal mouse transcriptome using PacBio long reads and illustrate how the tool is effective in readily describing the composition of and characterizing the full-length transcriptome. We perform extensive evaluation of ToFU PacBio transcripts by PCR to reveal that an important number of the novel transcripts are technical artifacts of the sequencing approach, and that SQANTI quality descriptors can be used to engineer a filtering strategy to remove them. Most novel transcripts in this curated transcriptome are novel combinations of existing splice sites, result more frequently in novel ORFs than novel UTRs and are enriched in both general metabolic and neural specific functions. We show that these new transcripts have a major impact in the correct quantification of transcript levels by state-of-the-art short-read based quantification algorithms. By comparing our iso-transcriptome with public proteomics databases we find that alternative isoforms are elusive to proteogenomics detection and are variable in protein changes with respect to the principal isoform of their genes. SQANTI allows the user to maximize the analytical outcome of long read technologies by providing the tools to deliver quality-evaluated and curated full-length transcriptomes. SQANTI is available athttps://bitbucket.org/ConesaLab/sqanti.
CNN-based Encoding and Decoding of Visual Object Recognition in Space and Time
Authors: Seeliger K. , Fritsche M. , Güçlü U. , Schoenmakers S. , Schoffelen J.-M. , Bosch S. E. , van Gerven M. A. J. 
Published: March 2017

AbstractDeep convolutional neural networks (CNNs) have been put forward as neurobiologically plausible models of the visual hierarchy. Using functional magnetic resonance imaging, CNN representations of visual stimuli have previously been shown to correspond to processing stages in the ventral and dorsal streams of the visual system. Whether this correspondence between models and brain signals also holds for activity acquired at high temporal resolution has been explored less exhaustively. Here, we addressed this question by combining CNN-based encoding models with magnetoencephalography (MEG). Human participants passively viewed 1000 images of objects while MEG signals were acquired. We modelled their high temporal resolution source-reconstructed cortical activity with CNNs, and observed a feedforward sweep across the visual hierarchy between 75-200 ms after stimulus onset. This spatiotemporal cascade was captured by the network layer representations, where the increasingly abstract stimulus representation in the hierarchical network model was reflected in different parts of the visual cortex, following the visual ventral stream. We further validated the accuracy of our encoding model by decoding stimulus identity in a left-out validation set of viewed objects, achieving state-of-the-art decoding accuracy.
A Species-Specific Nematocide that Results in Terminal Embryogenesis
Authors: Renahan Tess , Hong Ray L. 
Published: March 2017

AbstractNematode-insect interactions are ubiquitous, complex, and constantly changing as the host and nematode coevolve. The entomophilic nematodePristionchus pacificusis found on a myriad of beetle species worldwide, though the molecular dynamics of this relationship are largely unknown. To better understand how host cues affectP. pacificusembryogenesis, we characterized the threshold of sensitivity to the pheromone (Z)-7-tetradecen-2-one (ZTDO) by determining the minimum exposure duration and developmental window that results inP. pacificusembryonic lethality. We found early-stage embryos exposed to volatile ZTDO for as few as four hours all display terminal embryogenesis, characterized by punctuated development up to 48 hours later, with abnormal morphology and limited lumen formation. To determine if the pheromone arrests pre-hatching development by suffocating or permeabilizing the eggshells, we raised embryos under anoxic condition as well as examined eggshell permeability using the lipophilic dye FM4-64. We found that asphyxiating the embryos arrested embryogenesis in a reversible manner but did not phenocopy the effects of ZTDO exposure, whereas the ZTDO-induced disruption of embryogenesis did correlate with increased eggshell permeability. The effects of ZTDO are also highly specific, as other lipid insect compounds do not produce any detectable embryocidal effect. The high specificity and unusual teratogenic effect of ZTDO may be important in mediating the host-nematode relationship by regulatingP. pacificusdevelopment.Summary StatementInsect-associated nematodes coordinate their development using host cues to “walk the line” between mutualism and pathogenesis. A host pheromone causes terminal embryogenesis by permeablizing the nematode eggshell.
Eyes closed or Eyes open? Exploring the alpha desynchronization hypothesis in resting state functional connectivity networks with intracranial EEG
Authors: Gómez-Ramírez Jaime , Freedman Shelagh , Mateos Diego , Pérez-Velázquez José Luis , Valiante Taufik 
Published: March 2017

AbstractThis paper addresses a fundamental question, are eyes closed and eyes open resting states equivalent baseline conditions, or do they have consistently different electrophysiological signatures? We compare the functional connectivity patterns in an eyes closed resting state with an eyes open resting state, and show that functional connectivity in the alpha band decreases in the eyes open condition compared to eyes closed. This "alpha desynchronization " or reduction in the number of connections from eyes closed to eyes open, is here, for the first time, studied with intracranial recordings. We provide two calculations of the wiring cost, local and mesoscopic, defined in terms of the distance between the electrodes and the likelihood that they are functionally connected. We find that, in agreement with the "alpha desynchronization" hypothesis, the local wiring cost decreases going from eyes closed to eyes open. However, when the wiring cost calculation takes into account the connectivity pattern, the wiring cost variation from eyes closed to eyes open is not as consistent and shows regional specificity. The wiring cost measure defined here, provides a new avenue for understanding the electrophysiology of resting state.
Characterization of nitrogen deposition by means of atmospheric biomonitors
Authors: Díaz-Álvarez E. A. , de la Barrera E. 
Published: March 2017

AbstractAn increase of nitrogen deposition resulting from human activities is not only a major threat for global biodiversity, but also for human health, especially in highly populated regions. It is thus important and in some instances legally mandated to monitor reactive nitrogen species in the atmosphere. The utilization of widely distributed biological species suitable for biomonitoring may be a good alternative. We assessed the suitability of an ensemble of atmospheric biomonitors of nitrogen deposition by means of an extensive sampling of a lichen, two mosses, and a bromeliad throughout the Valley of Mexico, whose population reaches 30 million, and subsequent measurements of nitrogen metabolism parameters. In all cases we found significant responses of nitrogen content, C:N ratio and the δ15N to season and site. In turn, the δ15N for the mosses responded linearly to the wet deposition. Also, the nitrogen content (R2= 0.7), the C:N ratio (R2= 0.6), and δ15N (R2= 0.5) for the bromeliad had a linear response to NOx. However, the bromeliad was not found in sites with NOx concentrations exceeding 80 ppb, apparently of as a consequence of exceeding nitrogen. These biomonitors can be utilized in tandem to determine the status of atmospheric nitrogenous pollution in regions without monitoring networks for avoiding health problems for ecosystems and humans.
ChIPSeqFPro, a pipeline for sequential processing of ChIP-Seq fastq to bigwig files
Authors: Pjanic Milos 
Published: March 2017

AbstractChIPSeqFPro is a pipeline that automates processing of a collection of ChIPSeq or ATAC-Seq data starting from the gzip compressed fastq files. It performs the quality control using FastQC, mapping to the human genome hg19 or mouse mm10 using BWA mapper, for both single read or paired end sequencing fastq files, followed with sam to bam conversion using samtools view, creates statistics on bam files using samtools flagstat, peak calling with MACS, and finally creates high resolution bigwig files from bam files using a custom script bam2bigwig that invokes bedtools bamtobed and UCSC scripts, bedItemOverlapCount, bedGraphToBigWig and fetchChromSizes.
Genetic and epigenetic insight into morphospecies in a reef coral
Authors: Dimond James L. , Gamblewood Sanoosh K. , Roberts Steven B. 
Published: March 2017

AbstractIncongruence between conventional and molecular systematics has left the delineation of many species unresolved. Reef-building corals are no exception, with phenotypic plasticity among the most plausible explanations for alternative morphospecies. As potential molecular signatures of phenotypic plasticity, epigenetic processes may contribute to our understanding of morphospecies. We compared genetic and epigenetic variation in Caribbean branchingPoritesspp., testing the hypothesis that epigenetics— specifically, differential patterns of DNA methylation—play a role in alternative morphotypes of a group whose taxonomic status has been questioned. We used reduced representation genome sequencing to analyze over 1,000 single nucleotide polymorphisms and CpG sites in 27Poritesspp. exhibiting a range of morphotypes from a variety of habitats in Belize. We found stronger evidence for genetic rather than epigenetic structuring, identifying three well-defined genetic groups. One of these groups exhibited significantly thicker branches, and branch thickness was a better predictor of genetic groups than depth, habitat, or symbiont type. Epigenetic patterns were more subtle, with no clear groups. The more thickly branched individuals in one of the genetic groups exhibited some epigenetic similarity, suggesting potential covariation of genetics and epigenetics. This covariation was further supported by a positive association between pairwise genetic and epigenetic distance. We speculate that epigenetic patterns are a complex mosaic reflecting inheritance and diverse environmental histories. Given the role of genetics in branchingPoritesspp. morphospecies we were able to detect with genome-wide sequencing, use of such techniques throughout the geographic range may help settle their phylogeny.
Antibody-mediated depletion of protein variant expression in living cells (Protein interference)
Authors: Ulaganathan Vijay K. , Ullrich Axel 
Published: March 2017

AbstractA significant development in the field of human biology is the revelation of millions of unannotated protein sequence variants emerging from the several human genotyping and genome sequencing initiatives. This presents unique opportunities as well as confounding challenges in our understanding of how molecular signalling outcomes vary among individuals in the general population. As a result the conventional ‘one drug fits all’ lines of approach in the drug discovery process is becoming obsolete. However, an innovative genotype-specific approach targeting protein sequence variants instead of a reference protein target is currently lacking. In this short communication we report a remarkable observation of antibody-mediated knockdown of intracellular protein expression. This suggests allele-specific inhibition of protein-variant expression can be achieved by intracellular delivery of lipid conjugated linear epitope-specific monoclonal antibodies. The results presented here demonstrate novel opportunities for interrogating the protein coding variations in the human genomes and new therapeutic strategies for the inhibition of pathogenic protein variants in a genotype-centric manner.
Expanding gene families helps generate the metabolic robustness required for antibiotic biosynthesis
Authors: Schniete Jana K , Cruz-Morales Pablo , Selem Nelly , Fernández-Martínez Lorena T. , Hunter Iain S , Barona-Gómez Francisco , Hoskisson Paul A 
Published: March 2017

Introductory paragraphExpanding the genetic repertoire of an organism by gene duplication or horizontal gene transfer (HGT) can aid adaptation.Streptomycesspecies are prolific producers of bioactive specialised metabolites with adaptive functions in nature and some have found utility in human medicine such as antibiotics. Whilst the biosynthesis of these specialised metabolites is directed by dedicated biosynthetic gene clusters (BGCs), little attention has been focussed on how these organisms have evolved robustness into their genomes to facilitate the metabolic plasticity required to provide chemical precursors for biosynthesis. Here we show that specific expansions of gene families in central carbon metabolism have evolved and become fixed inStreptomycesbacteria to enable plasticity and robustness that maintain cell functionality whilst costly specialised metabolites are produced. These expanded gene families, in addition to being a metabolic adaptation, make excellent targets for metabolic engineering of industrial specialised metabolite producing bacteria.
Data-Driven Prediction of CRISPR-Based Transcription Regulation for Programmable Control of Metabolic Flux
Authors: Sheng Jiayuan , Guo Weihua , Ash Christine , Freitas Brendan , Paoletti Mitchell , Feng Xueyang 
Published: March 2017

AbstractMultiplex and multi-directional control of metabolic pathways is crucial for metabolic engineering to improve product yield of fuels, chemicals, and pharmaceuticals. To achieve this goal, artificial transcriptional regulators such as CRISPR-based transcription regulators have been developed to specifically activate or repress genes of interest. Here, we found that by deploying guide RNAs to target on DNA sites at different locations of genetic cassettes, we could use just one synthetic CRISPR-based transcriptional regulator to simultaneously activate and repress gene expressions. By using the pairwise datasets of guide RNAs and gene expressions, we developed a data-driven predictive model to rationally design this system for fine-tuning expression of target genes. We demonstrated that this system could achieve programmable control of metabolic fluxes when using yeast to produce versatile chemicals. We anticipate that this master CRISPR-based transcription regulator will be a valuable addition to the synthetic biology toolkit for metabolic engineering, speeding up the “design-build-test” cycle in industrial biomanufacturing as well as generating new biological insights on the fates of eukaryotic cells.