bluuebunny/crossref_metadata_2025_split huggingface dataset:
Build a Better Bootstrap and the RAWR Shall Beat a Random Path to Your Door: Phylogenetic Support Estimation Revisited
Authors: Wang Wei , Liu Kevin J. 
Published: February 2020

AbstractMotivationThe standard bootstrap method is used throughout science and engineering to perform general-purpose non-parametric resampling and re-estimation. Among the most widely cited and widely used such applications is the phylogenetic bootstrap method, which Felsenstein proposed in 1985 as a means to place statistical confidence intervals on an estimated phylogeny (or estimate “phylogenetic support”). A key simplifying assumption of the bootstrap method is that input data are independent and identically distributed (i.i.d.). However, the i.i.d. assumption is an over-simplification for biomolecular sequence analysis, as Felsenstein noted. Special-purpose fully parametric or semi-parametric methods for phylogenetic support estimation have since been introduced, some of which are intended to address this concern.ResultsIn this study, we introduce a new sequence-aware non-parametric resampling technique, which we refer to as RAWR (“RAndom Walk Resampling”). RAWR consists of random walks that synthesize and extend the standard bootstrap method and the “mirrored inputs” idea of Landan and Graur. We apply RAWR to the task of phylogenetic support estimation. RAWR’s performance is compared to the state of the art using synthetic and empirical data that span a range of dataset sizes and evolutionary divergence. We show that RAWR support estimates offer comparable or typically superior type I and type II error compared to phylogenetic bootstrap support as well as GUIDANCE2, a state-of-the-art purpose-built fully parametric method. Additional simulation study experiments help to clarify practical considerations regarding RAWR support estimation. We conclude with thoughts on future research directions and the untapped potential for sequence-aware non-parametric resampling and re-estimation.AvailabilityData and software are publicly available under open-source software and open data licenses at:https://gitlab.msu.edu/liulab/RAWR-study-datasets-and-scripts.Contactkjl@msu.edu
Genomic variance of the 2019-nCoV coronavirus
Authors: Ceraolo Carmine , Giorgi Federico M. 
Published: February 2020

AbstractThere is rising global concern for the recently emerged novel Coronavirus (2019-nCov). Full genomic sequences have been released by the worldwide scientific community in the last few weeks in order to understand the evolutionary origin and molecular characteristics of this virus. Taking advantage of all the genomic information currently available, we constructed a phylogenetic tree including also representatives of othercoronaviridae, such as Bat coronavirus (BCoV) and SARS. We confirm high sequence similarity (>99%) between all sequenced 2019-nCoVs genomes available, with the closest BCoV sequence sharing 96.2% sequence identity, confirming the notion of a zoonotic origin of 2019-nCoV. Despite the low heterogeneity of the 2019-nCoV genomes, we could identify at least two hyper-variable genomic hotspots, one of which is responsible for a Serine/Leucine variation in the viral ORF8-encoded protein. Finally, we perform a full proteomic comparison with othercoronaviridae, identifying key aminoacidic differences to be considered for antiviral strategies deriving from previous anti-coronavirus approaches.
Estimating maximum sustainable yield of snow crab (Chionoecetes opilio) off Tohoku Japan via a state-space assessment model with time-varying natural mortality
Authors: Shibata Yasutoki , Nagao Jiro , Narimatsu Yoji , Morikawa Eisuke , Suzuki Yuto , Tokioka Shun , Yamada Manabu , Kakehi Shigeho , Okamura Hiroshi 
Published: February 2020

AbstractYield from fisheries is a tangible benefit of ecosystem services and sustaining or restoring a fish stock level to achieve a maximum sustainable yield (MSY). Snow crab (Chionoecetes opilio) off Tohoku has been managed by a total allowable catch since 1996, although their abundance has not increased even after 2011, when fishing pressure rapidly decreased because of the Great East Japan Earthquake. This implies that their biological characteristics, such as recruits, natural mortality coefficient (M), and terminal molting probabilities (p), might have changed. We developed “just another state-space stock assessment model (JASAM)” to estimate the MSY of the snow crab off Tohoku, Japan, considering interannual variations inMandp. The multi-model inference revealed thatMincreased from 0.2 in 1997 to 0.59 in 2018, although it was not different among the instars, sex, nor terminal molt of crabs. The parameterpalso increased by 1.34–2.46 times depending on the instar growth stages from 1997 to 2018. We estimated the MSYs in three scenarios, which drastically changed ifMandpwere set as they were in the past or at the current values estimated from this study. This result indicated that the MSY of snow crab would also be time-varying based on their time-varying biological characteristics.
Germline inherited small RNAs clear untranslated maternal mRNAs inC. elegansembryos
Authors: Quarato Piergiuseppe , Singh Meetali , Cornes Eric , Li Blaise , Bourdon Loan , Mueller Florian , Didier Celine , Cecere Germano 
Published: February 2020

ABSTRACTInheritance and clearance of maternal mRNAs are two of the most critical events required for animal early embryonic development. However, the mechanisms regulating this process are still largely unknown. Here, we show that together with maternal mRNAs,C. elegansembryos inherit a complementary pool of small non-coding RNAs capable of triggering the cleavage and removal of hundreds of maternal mRNAs. These antisense small RNAs are loaded into the maternal catalytically-active Argonaute CSR-1 and cleave complementary mRNAs no longer engaged in translation in somatic blastomeres. Induced depletion of CSR-1 specifically during embryonic development leads to embryonic lethality in a slicer-dependent manner and impairs the degradation of CSR-1 embryonic mRNA targets. Given the conservation of Argonaute catalytic activity, we propose that a similar mechanism operates to clear maternal mRNAs during the maternal-to-zygotic transition across species.
Dynamics ofmcr-1prevalence andmcr-1-positiveEscherichia coliafter the cessation of colistin use as a feed additive for animals in China: a prospective cross-sectional and whole genome sequencing based molecular epidemiological study
Authors: Shen Cong , Zhong Lan-Lan , Yang Yongqiang , Doi Yohei , Paterson David L , Stoesser Nicole , Ma Furong , Ahmed Mohamed Abd El-Gawad El-Sayed , Feng Siyuan , Huang Songying , Li Hong-Yu , Huang Xi , Wen Xin , Zhao Zihan , Lin Minmin , Chen Guanping , Liang Wanfei , Liang Yingjian , Xia Yong , Dai Min , Chen Ding-Qiang , Zhang Liyan , Liao Kang , Tian Guo-Bao 
Published: February 2020

AbstractBackgroundThe global dissemination of colistin resistance encoded bymcr-1has been attributed to extensive use of colistin in livestock, threatening colistin efficacy in medicine. The emergence ofmcr-1in common pathogens, such asEscherichia coli, is of particular concern. Therefore, China banned the use of colistin in animal feed from May 1ST2017. We investigated subsequent changes inmcr-1prevalence, and the genomic epidemiology ofmcr-1-positiveEscherichia coli(MCRPEC).MethodsSampling was conducted pre- (October-December 2016) and post-colistin ban (October-December, 2017 and 2018, respectively). 3675 non-duplicate pig fecal samples were collected from 14 provinces (66 farms) in China to determine intervention-related changes inmcr-1prevalence. 15193 samples were collected from pigs, healthy human volunteers, colonized and infected hospital inpatients, food and the environment in Guangzhou, to characterize source-specificmcr-1prevalence and the wider ecological impact of the ban. From these samples, 688 MCRPEC were analyzed with whole genome sequencing (WGS), plasmid conjugation and S1-PFGE/Southern blots to characterize associated genomic changes.FindingsAfter the ban,mcr-1prevalence decreased significantly in national pig farms, from 45·0% (308/684 samples) in 2016, to 19·4% (274/1416) in 2018 (p<0·0001). This trend was mirrored in samples from most sources in Guangzhou (overall 19·2% [959/5003 samples] in 2016; 5·3% [238/4489] in 2018; p<0·0001). The population structure of MCRPEC was diverse (23 sequence clusters [SCs]); ST10 clonal complex isolates were predominant (247/688 [36%]). MCRPEC causing infection in hospitalized inpatients were genetically more distinct and appeared less affected by the ban.mcr-1was predominantly found on plasmids (632/688 [92%]). Commonmcr-1plasmid types included IncX4, IncI2 and IncHI2 (502/656 [76.5%]); significant increases in IncI2-associatedmcr-1and a distinct lineage ofmcr-1-associated IncHI2 were observed post-ban. Changes in the frequency ofmcr-1-associated flanking sequences (ISApl1-negative MCRPEC), 63 core genome SNPs and 30 accessory genes were also significantly different after the ban, consistent with rapid genetic adaptation in response to changing selection pressures.InterpretationA rapid, ecosystem-wide, decline inmcr-1was observed after banning the use of colistin in animal feed, with associated genetic changes in MCRPEC. Genomic surveillance is key to assessing and monitoring stewardship interventions.FundingNational Natural Science Foundation of China
A Hierarchical Approach Using Marginal Summary Statistics for Multiple Intermediates in a Mendelian Randomization or Transcriptome Analysis
Authors: Jiang Lai , Xu Shujing , Mancuso Nicholas , Newcombe Paul J. , Conti David V. 
Published: February 2020

AbstractBackgroundPrevious research has demonstrated the usefulness of hierarchical modeling for incorporating a flexible array of prior information in genetic association studies. When this prior information consists of effect estimates from association analyses of single nucleotide polymorphisms (SNP)-intermediate or SNP-gene expression, a hierarchical model is equivalent to a two-stage instrumental or transcriptome-wide association study (TWAS) analysis, respectively.MethodsWe propose to extend our previous approach for the joint analysis of marginal summary statistics (JAM) to incorporate prior information via a hierarchical model (hJAM). In this framework, the use of appropriate effect estimates as prior information yields an analysis similar to Mendelian Randomization (MR) and TWAS approaches such as FUSION and S-PrediXcan. However,hJAMis applicable to multiple correlated SNPs and multiple correlated intermediates to yield conditional estimates of effect for the intermediate on the outcome, thus providing advantages over alternative approaches.ResultsWe investigate the performance ofhJAMin comparison to existing MR approaches (inverse-variance weighted MR and multivariate MR) and existing TWAS approaches (S-PrediXcan) for effect estimation, type-I error and empirical power. We applyhJAMto two examples: estimating the conditional effects of body mass index and type 2 diabetes on myocardial infarction and estimating the effects of the expressions of geneNUCKS1andPM20D1on the risk of prostate cancer.ConclusionsAcross numerous causal simulation scenarios, we demonstrate thathJAMis unbiased, maintains correct type-I error and has increased power.Key MessagesMendelian randomization and transcriptome-wide association studies (TWAS) can be viewed as similar approaches via a hierarchical model.The hierarchal joint analysis of marginal summary statistics (hJAM) is a multivariate Mendelian randomization approach which offers a simple way to address the pleiotropy bias that is introduced by genetic variants associated with multiple risk factors or expressions of genes.hJAMincorporates the linkage disequilibrium structure of the single nucleotide polymorphism (SNPs) in a reference population to account for the correlation between SNPs.In addition to Mendelian randomization and TWAS,hJAMoffers flexibility to incorporate functional or genomic annotation or information from metabolomic studies.
A mouse SWATH-MS reference spectral library enables deconvolution of species-specific proteomic alterations in human tumour xenografts
Authors: Krasny Lukas , Bland Philip , Burns Jessica , Lima Nadia Carvalho , Harrison Peter T. , Pacini Laura , Elms Mark L. , Ning Jian , Garcia Martinez Victor , Yu Yi-Ru , Acton Sophie E. , Ho Ping-Chih , Calvo Fernando , Swain Amanda , Howard Beatrice A. , Natrajan Rachael C. , Huang Paul H. 
Published: February 2020

AbstractSWATH-mass spectrometry (MS) enables accurate and reproducible proteomic profiling in multiple model organisms including the mouse. Here we present a comprehensive mouse reference spectral library (MouseRefSWATH) that permits quantification of up to 10,597 proteins (62.2% of the mouse proteome) by SWATH-MS. We exploit MouseRefSWATH to develop an analytical pipeline for species-specific deconvolution of proteomic alterations in human tumour xenografts (XenoSWATH). This method overcomes the challenge of high sequence similarity between mouse and human proteins, facilitating the study of host microenvironment-tumour interactions from ‘bulk tumour’ measurements. We apply the XenoSWATH pipeline to characterise an intraductal xenograft model of breast ductal carcinoma in-situ and uncover complex regulation of cell migration pathways that are not restricted to tumour cells but also operate in the mouse stroma upon progression to invasive disease. MouseRefSWATH and XenoSWATH opens new opportunities for in-depth and reproducible proteomic assessment to address wide-ranging biological questions involving this important model organism.
Impact of immediate cryopreservation on the establishment of patient derived xenografts from head and neck cancer patients
Authors: Abel Lindsey , Durmaz Arda , Hu Rong , Longhurst Colin , Baschnagel Andrew M. , Wheeler Deric , Scott Jacob G. , Kimple Randall J. 
Published: February 2020

AbstractBackgroundPatient-derived xenografts established from human cancers are important tools for investigating novel anti-cancer therapies. Establishing PDXs requires a significant investment and many PDXs may be used infrequently due to their similarity to existing models, their growth rate, or the lack of relevant mutations. We performed this study to determine whether we could efficiently establish PDXs after cryopreservation to allow molecular profiling to be completed prior to implanting the human cancer.MethodsFresh tumor was split with half used to establish a PDX immediately and half cryopreserved for later implantation. Resulting tumors were assessed histologically and tumors established from fresh or cryopreserved tissues compared as to the growth rate, extent of tumor necrosis, mitotic activity, keratinization, and grade. All PDXs were subjected to short tandem repeat testing to confirm identity and assess similarity between methods.ResultsTumor growth was seen in 70% of implanted cases. No growth in either condition was seen in 30% of tumors. One developed a SCC from the immediate implant but a lymphoproliferative mass without SCC from the cryopreserved specimen. No difference in growth rate was seen. No difference between histologic parameters was seen between the two approaches.ConclusionsFresh human cancer tissue can be immediately cryopreserved and later thawed and implanted to establish PDXs. This resource saving approach allows for tumor profiling prior to implantation into animals thus maximizing the probability that the tumor will be utilized for future research.
Neuroligin dependence of social behaviour inC. elegansprovides a model to investigate an autism associated gene
Authors: Rawsthorne Helena , Calahorro Fernando , Feist Emily , Holden-Dye Lindy , O’Connor Vincent , Dillon James 
Published: February 2020

AbstractAutism spectrum disorder (ASD) is characterised by a triad of behavioural impairments including social behaviour. Neuroligin, a trans-synaptic adhesion molecule, has emerged as a penetrant genetic determinant of behavioural traits that signature the neuroatypical behaviours of autism. However, the function of neuroligin in social circuitry and the impact of genetic variation to this gene is not fully understood. Indeed, in animal studies designed to model autism there remains controversy regarding the role of neuroligin dysfunction in the expression of disrupted social behaviours. The model organism,C. elegans,offers an informative experimental platform to investigate the impact of genetic variants on social behaviour. In a number of paradigms it has been shown that inter-organismal communication by chemical cues regulatesC. eleganssocial behaviour. We utilise this social behaviour to investigate the effect of autism associated genetic variants within the social domain of the research domain criteria. We have identified neuroligin as an important regulator of social behaviour and segregate the importance of this gene to the recognition and/or processing of social cues. We also use CRISPR/Cas9 to edit an R-C mutation that mimics a highly penetrant human mutation associated with autism.C. eleganscarrying this mutation phenocopy the behavioural dysfunction of aC. elegansneuroligin null mutant, thus confirming its significance in the regulation of animal social biology. This highlights that quantitative behaviour and precision genetic intervention can be used to manipulate discrete social circuits of the worm to provide further insight to complex social behaviour.
Perinatal THC Exposure via Lactation Induces Lasting Alterations to Social Behavior and Prefrontal Cortex Function in Rats at Adulthood
Authors: Scheyer Andrew F , Borsoi Milene , Manzoni Olivier JJ 
Published: February 2020

AbstractCannabis is the world’s most widely abused illicit drug and consumption amongst women during and surrounding the period of pregnancy is increasing. Previously, we have shown that cannabinoid exposure via lactation during the early postnatal period disrupts early developmental trajectories of prefrontal cortex maturation and induces behavioral abnormalities during the first weeks of life in male and female rat progeny. Here, we investigated the lasting consequences of this postnatal cannabinoid exposure on synaptic and behavioral parameters in the adult offspring of Δ9-tetrahydrocannabinol (THC)-treated dams. At adulthood, these perinatally THC-exposed rats exhibits deficits in social discrimination accompanied by an overall augmentation of social exploratory behavior. These behavioral alterations were further correlated with multiple abnormalities in synaptic plasticity in the prefrontal cortex, including lost endocannabinoid-mediated long-term depression (LTD), lost long-term potentiation and augmented mGlu2/3-LTD. Finally, basic parameters of intrinsic excitability at prefrontal cortex pyramidal neurons were similarly altered by the perinatal THC exposure. Thus, perinatal THC exposure via lactation induces lasting deficits in behavior and synaptic function which persist into adulthood life in male and female progeny.
New Tools for Hop Cytogenomics: Identification of Tandem Repeat Families from Long-Read Sequences ofHumulus lupulus
Authors: Easterling Katherine A. , Pitra Nicholi J. , Morcol Taylan B. , Aquino Jenna R. , Lopes Lauren G. , Bussey Kristin C. , Matthews Paul D. , Bass Hank W. 
Published: February 2020

ABSTRACTHop (Humulus lupulusL.) is known for its use as a bittering agent in beer and has a rich history of cultivation, beginning in Europe and now spanning the globe. There are five wild varieties worldwide, which may have been introgressed with cultivated varieties. As a dioecious species, its obligate outcrossing, non-Mendelian inheritance, and genomic structural variability have confounded directed breeding efforts. Consequently, understanding genome evolution in Humulus represents a considerable challenge, requiring additional resources, including integrated genome maps. In order to facilitate cytogenetic investigations into the transmission genetics of hop, we report here the identification and characterization of 17 new and distinct tandem repeat sequence families. A tandem repeat discovery pipeline was developed using k-mer filtering and dot plot analysis of PacBio long-read sequences from the hop cultivar Apollo. We produced oligonucleotide FISH probes from conserved regions of HuluTR120 and HulTR225 and demonstrated their utility to stain meiotic chromosomes from wild hop, var. neomexicanus. The HuluTR225 FISH probe hybridized to several loci per nucleus and exhibited irregular, non-Mendelian transmission in male meiocytes of wild hop. Collectively, these tandem repeat sequence families not only represent unique and valuable new cytogenetic reagents but also have the capacity to inform genome assembly efforts and support comparative genomic analyses.
Identifiability and experimental design in perturbation studies
Authors: Gross Torsten , Blüthgen Nils 
Published: February 2020

AbstractMotivationA common strategy to infer and quantify interactions between components of a biological system is to deduce them from the network’s response to targeted perturbations. Such perturbation experiments are often challenging and costly. Therefore, optimising the experimental design is essential to achieve a meaningful characterisation of biological networks. However, it remains difficult to predict which combination of perturbations allows to infer specific interaction strengths in a given network topology. Yet, such a description of identifiability is necessary to select perturbations that maximize the number of inferable parameters.ResultsWe show analytically that the identifiability of network parameters can be determined by an intuitive maximum flow problem. Furthermore, we used the theory of matroids to describe identifiability relationships between sets of parameters in order to build identifiable effective network models. Collectively, these results allowed to device strategies for an optimal design of the perturbation experiments. We benchmarked these strategies on a database of human pathways. Remarkably, full network identifiability was achieved with on average less than a third of the perturbations that are needed in a random experimental design. Moreover, we determined perturbation combinations that additionally decreased experimental effort compared to single-target perturbations. In summary, we provide a framework that allows to infer a maximal number of interaction strengths with a minimal number of perturbation experiments.AvailabilityIdentiFlow is available atgithub.com/GrossTor/IdentiFlow.Contactnils.bluethgen@charite.de
Imaging mass spectrometry and shotgun proteomics reveal dysregulated pathways in hormone induced male infertility
Authors: Lahiri Shibojyoti , Walenta Lena , Aftab Wasim , Strauss Leena , Poutanen Matti , Mayerhofer Artur , Imhof Axel 
Published: February 2020

AbstractSpermatogenesis is a complex multi-step process involving intricate interactions between different cell types in the male testis. Disruption of these interactions results in infertility. Combination of shotgun tissue proteomics with MALDI imaging mass spectrometry is markedly potent in revealing topological maps of molecular processes within tissues. Here, we use a combinatorial approach on a characterized mouse model of hormone induced male infertility to uncover misregulated pathways. Comparative testicular proteome of wildtype and mice overexpressing human P450 aromatase (AROM+) with pathologically increased estrogen levels unravels gross dysregulation of spermatogenesis and emergence of proinflammatory pathways in AROM+ testis.In situMS allowed us to localize misregulated proteins/peptides to defined regions within the testis. Results suggest that infertility is associated with substantial loss of proteomic heterogeneity, which define distinct stages of seminiferous tubuli in healthy animals. Importantly, considerable loss of mitochondrial factors, proteins associated with late stages of spermatogenesis and steroidogenic factors characterise AROM+ mice. Thus, the novel proteomic approach pinpoints in unprecedented ways the disruption of normal processes in testis and provides a signature for male infertility.