bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fast Numerical Optimization for Genome Sequencing Data in Population Biobanks
Authors: Li Ruilin , Chang Christopher , Tanigawa Yosuke , Narasimhan Balasubramanian , Hastie Trevor , Tibshirani Robert , Rivas Manuel A. 
Published: February 2021

AbstractWe develop two efficient solvers for optimization problems arising from large-scale regularized regressions on millions of genetic variants sequenced from hundreds of thousands of individuals. These genetic variants are encoded by the values in the set {0, 1, 2,NA}. We take advantage of this fact and use two bits to represent each entry in a genetic matrix, which reduces memory requirement by a factor of 32 compared to a double precision floating point representation. Using this representation, we implemented an iteratively reweighted least square algorithm to solve Lasso regressions on genetic matrices, which we namesnpnet-2.0. When the dataset contains many rare variants, the predictors can be encoded in a sparse matrix. We utilize the sparsity in the predictor matrix to further reduce memory requirement and computational speed. Our sparse genetic matrix implementation uses both the compact 2-bit representation and a simplified version of compressed sparse block format so that matrix-vector multiplications can be effectively parallelized on multiple CPU cores. To demonstrate the effectiveness of this representation, we implement an accelerated proximal gradient method to solve group Lasso on these sparse genetic matrices. This solver is namedsparse-snpnet, and will also be included as part ofsnpnetR package. Our implementation is able to solve group Lasso problems on sparse genetic matrices with more than 1, 000, 000 columns and almost 100, 000 rows within 10 minutes and using less than 32GB of memory.
Long-reads are revolutionizing 20 years of insect genome sequencing
Authors: Hotaling Scott , Sproul John S. , Heckenhauer Jacqueline , Powell Ashlyn , Larracuente Amanda M. , Pauls Steffen U. , Kelley Joanna L. , Frandsen Paul B. 
Published: February 2021

AbstractThe first insect genome (Drosophila melanogaster) was published two decades ago. Today, nuclear genome assemblies are available for a staggering 601 insect species representing 20 orders. In this study, we analyzed the most-contiguous assembly for each species and provide a “state of the field” perspective, emphasizing taxonomic representation, assembly quality, gene completeness, and sequencing technologies. Relative to species richness, genomic efforts have been biased towards four orders (Diptera, Hymenoptera, Collembola, and Phasmatodea), Coleoptera are underrepresented, and 11 orders still lack a publicly available genome assembly. The average insect genome assembly is 439.2 megabases in length with 87.5% of single-copy benchmarking genes intact. Most notable has been the impact of long-read sequencing; assemblies that incorporate long-reads are ~48x more contiguous than those that do not. We offer four recommendations as we collectively continue building insect genome resources: (1) seek better integration between independent research groups and consortia, (2) balance future sampling between filling taxonomic gaps and generating data for targeted questions, (3) take advantage of long read sequencing technologies, and (4) expand and improve gene annotations.Significance statementSince the first insect genome was sequenced ~20 years ago, sequencing technologies and the availability of insect genome assemblies have both advanced dramatically. In this study, we curated, analyzed, and summarized the field of insect genomics in terms of taxonomic representation, assembly quality, gene completeness, and sequencing technology. We show that 601 insect species have genome assemblies available, with some groups heavily overrepresented (e.g., Diptera) relative to others (e.g., Coleoptera). The major takeaway of our study is that genome assemblies produced with long reads are ~48x more contiguous than short read assemblies.
Expanding theMECP2network using comparative genomics reveals potential therapeutic targets for Rett syndrome
Authors: Unterman Irene , Bloch Idit , Cazacu Simona , Kazimirsky Gila , Berman Benjamin P. , Ben-Zeev Bruria , Brodie Chaya , Tabach Yuval 
Published: February 2021

AbstractInactivating mutations in the Methyl-CpG Binding Protein 2 (MECP2) gene are the main cause of Rett syndrome (RTT). Despite extensive research into MECP2 function, no treatments for RTT are currently available. Here we use an evolutionary genomics approach to construct an unbiased MECP2 gene network, using 1,028 eukaryotic genomes to prioritize proteins with strong co-evolutionary signatures with MECP2. Focusing on proteins targeted by FDA approved drugs led to three promising candidates, two of which were previously linked to MECP2 function (IRAK, KEAP1) and one that was not (EPOR). We show that each of these compounds has the ability to rescue different phenotypes of MECP2 inactivation in cultured human neural cell types, and appear to act on Nuclear Factor Kappa B (NF-κB) signaling in inflammation. This study highlights the potential of comparative genomics to accelerate drug discovery, and yields potential new avenues for the treatment of RTT.Abstract Figure
c-Rel is required for IL-33-dependent activation of ILC2s
Authors: Zaini Aidil , Fulford Thomas S. , Grumont Raelene J. , Runting Jessica , Rodrigues Grace , Ng Judy , Gerondakis Steve , Zaph Colby , Scheer Sebastian 
Published: February 2021

AbstractGroup 2 innate lymphoid cells (ILC2s) are emerging as important cellular regulators of homeostatic and disease-associated immune processes. The cytokine interleukin-33 (IL-33) promotes ILC2-dependent inflammation and immunity, with IL-33 having been shown to activate NF-κB in a wide variety of cell types. However, it is currently unclear which NF-κB members play an important role in IL-33-dependent ILC2 biology. Here, we identify the NF-κB family member c-Rel as a critical component of the IL-33-dependent activation of ILC2s. Although c-Rel is dispensable for ILC2 development, it is critical for ILC2 function in the lung, with c-Rel-deficient (c-Rel–/–) mice resistant to papain- and IL-33-induced lung inflammation. We also show that the absence of c-Rel reduces the IL-33-dependent expansion of ILC2 precursors and lower levels of IL-5 and IL-13 cytokine production by mature ILC2s in the lung. Together, these results identify the IL-33-c-Rel axis as a central control point of ILC2 activation and function.
Effects of kinship correction on inflation of genetic interaction statistics in commonly used mouse populations
Authors: Tyler Anna L. , El Kassaby Baha , Kolishovski Georgi , Emerson Jake , Wells Ann , Mahoney J. Matthew , Carter Gregory W. 
Published: February 2021

AbstractIt is well understood that variation in relatedness among individuals, or kinship, can lead to false genetic associations. Multiple methods have been developed to adjust for kinship while maintaining power to detect true associations. However, relatively unstudied, are the effects of kinship on genetic interaction test statistics. Here we performed a survey of kinship effects on studies of six commonly used mouse populations. We measured inflation of main effect test statistics, genetic interaction test statistics, and interaction test statistics reparametrized by the Combined Analysis of Pleiotropy and Epistasis (CAPE). We also performed linear mixed model (LMM) kinship corrections using two types of kinship matrix: an overall kinship matrix calculated from the full set of genotyped markers, and a reduced kinship matrix, which left out markers on the chromosome(s) being tested. We found that test statistic inflation varied across populations and was driven largely by linkage disequilibrium. In contrast, there was no observable inflation in the genetic interaction test statistics. CAPE statistics were inflated at a level in between that of the main effects and the interaction effects. The overall kinship matrix overcorrected the inflation of main effect statistics relative to the reduced kinship matrix. The two types of kinship matrices had similar effects on the interaction statistics and CAPE statistics, although the overall kinship matrix trended toward a more severe correction. In conclusion, we recommend using a LMM kinship correction for both main effects and genetic interactions and further recommend that the kinship matrix be calculated from a reduced set of markers in which the chromosomes being tested are omitted from the calculation. This is particularly important in populations with substantial population structure, such as recombinant inbred lines in which genomic replicates are used.
Community end-of-life care during the COVID-19 pandemic: Initial findings of a UK primary care survey
Authors: Mitchell Sarah , Oliver Phillip , Gardiner Clare , Chapman Helen , Khan Dena , Boyd Kirsty , Dale Jeremy , Barclay Stephen , Mayland Catriona 
Published: February 2021

AbstractBackgroundThousands of people in the UK have required end-of-life care in the community during the COVID-19 pandemic. Primary healthcare teams (general practice and community nursing services) have provided the majority of this care, alongside specialist colleagues. There is a need to learn from this experience in order to inform future service delivery and planning.AimTo understand the views of general practitioners and community nurses providing end-of-life care during the first wave of the COVID-19 pandemic.Design and SettingA web-based, UK-wide questionnaire survey circulated via professional general practice and community nursing networks during September and October 2020.MethodResponses were analysed using descriptive statistics and an inductive thematic analysis.ResultsValid responses were received from 559 individuals (387 community nurses, 156 General Practitioners (GPs) and 16 unspecified role), from all regions of the UK. The majority reported increased involvement in providing community end-of-life care. Contrasting and potentially conflicting roles emerged between GPs and community nurses. There was increased use of remote consultations, particularly by GPs. Community nurses took greater responsibility in most aspects of end-of-life care practice, particularly face-to-face care, but reported feeling isolated. For some GPs and community nurses, there has been considerable emotional distress.ConclusionPrimary healthcare services are playing a critical role in meeting increased need for end-of-life care in the community during the COVID-19 pandemic. They have adapted rapidly, but the significant emotional impact, especially for community nurses, needs addressing alongside rebuilding trusting and supportive team dynamics.How this fits in (4 sentences)This study provides insights into experiences of delivering end-of-life care in the community during the first wave of the COVID-19 pandemic from the perspectives of UK general practitioners (GPs) and community nurses.Services have changed and adapted rapidly to meet increased need in terms of both volume and complexity, with community nurses taking greater responsibility for most areas of palliative care clinical practice, and GPs undertaking more care planning conversations.While GPs and specialist palliative care services conducted more remote consultations, community nurses carried out face-to-face end-of-life care and reported a feeling of isolation.As the pandemic progresses, and the increased need for end-of-life care in the community persists, more effective service models and multi-disciplinary teamwork in primary care are urgently needed.
Anterior eye development in the brown anole,Anolis sagrei
Authors: Rasys Ashley M. , Pau Shana H. , Irwin Katherine E. , Luo Sherry , Menke Douglas B. , Lauderdale James D. 
Published: February 2021

AbstractBackgroundAnterior eye development has been explored in different vertebrate species ranging from fish to mammals. However, missing from this diverse group is a representative of reptiles. A promising candidate to fill this void is the brown anole,Anolis sagrei, which is easily raised in the laboratory and for which genome editing techniques exist. Here we provide a detailed histological analysis of the development of the anterior structures of the eye inA. sagrei, which include the cornea, iris, ciliary body, lens, trabecular meshwork, and sclera ossicles.ResultsDevelopment of the anterior segment in Anoles proceeds as for other vertebrates with the lens forming first followed by the cornea, then the iris, ciliary body, trabecular meshwork, and sclera ossicles. The onset of these latter structures occurs first temporally than nasally. Unlike the eyes of mammals and birds, anoles possess a remarkably thin cornea, flat ciliary body, and a trabecular meshwork that lacks an obvious Schlemm’s canal.ConclusionsThis study highlights several features present in anoles and represents an important step towards understanding reptile eye development.Key FindingsThe anole cornea epithelium is thin, composed mainly of a single basal cell layer.The ciliary body lacks a ciliary process.Iris and ciliary body formation occur in a spatiotemporal fashion, developing first temporally then nasally.The anole trabecular meshwork is composed of a spongiform tissue and lacks a Schlemm’s canal.
Parasite co-opts a ubiquitin receptor to induce a plethora of developmental changes
Authors: Huang Weijie , MacLean Allyson M. , Sugio Akiko , Maqbool Abbas , Busscher Marco , Cho Shu-Ting , Kamoun Sophien , Kuo Chih-Horng , Immink Richard G.H. , Hogenhout Saskia A. 
Published: February 2021

AbstractObligate parasites can induce complex and substantial phenotypic changes in their hosts in ways that favour their transmission to other trophic levels. However, mechanisms underlying these changes remain largely unknown. Here, we demonstrate how SAP05 protein effectors from insect-vectored plant pathogenic phytoplasmas take control of several plant developmental processes to simultaneously prolong host lifespan and induce witch’s broom-like proliferations of leaf and sterile shoots, organs colonized by phytoplasmas and vectors. SAP05 acts by mediating the concurrent degradation of SPL and GATA developmental regulators via a process that uniquely relies on hijacking the plant ubiquitin receptor RPN10 independently of substrate lysine ubiquitination. RPN10 is highly conserved among eukaryotes, but SAP05 does not bind insect vector RPN10. A two-amino-acid substitution within plant RPN10 generates a functional variant that is resistant to SAP05 activities. Therefore, one effector protein enables obligate parasitic phytoplasmas to induce a plethora of developmental phenotypes in their hosts.
Comparative Analysis of common alignment tools for single cell RNA sequencing
Authors: Brüning Ralf Schulze , Tombor Lukas , Schulz Marcel H. , Dimmeler Stefanie , John David 
Published: February 2021

AbstractWith the rise of single cell RNA sequencing new bioinformatic tools became available to handle specific demands, such as quantifying unique molecular identifiers and correcting cell barcodes. Here, we analysed several datasets with the most common alignment tools for scRNA-seq data. We evaluated differences in the whitelisting, gene quantification, overall performance and potential variations in clustering or detection of differentially expressed genes.We compared the tools Cell Ranger 5, STARsolo, Kallisto and Alevin on three published datasets for human and mouse, sequenced with different versions of the 10X sequencing protocol.Striking differences have been observed in the overall runtime of the mappers. Besides that Kallisto and Alevin showed variances in the number of valid cells and detected genes per cell. Kallisto reported the highest number of cells, however, we observed an overrepresentation of cells with low gene content and unknown celtype. Conversely, Alevin rarely reported such low content cells.Further variations were detected in the set of expressed genes. While STARsolo, Cell Ranger 5 and Alevin released similar gene sets, Kallisto detected additional genes from the Vmn and Olfr gene family, which are likely mapping artifacts. We also observed differences in the mitochondrial content of the resulting cells when comparing a prefiltered annotation set to the full annotation set that includes pseudogenes and other biotypes.Overall, this study provides a detailed comparison of common scRNA-seq mappers and shows their specific properties on 10X Genomics data.Key messagesMapping and gene quantifications are the most resource and time intensive steps during the analysis of scRNA-Seq data.The usage of alternative alignment tools reduces the time for analysing scRNA-Seq data.Different mapping strategies influence key properties of scRNA-SEQ e.g. total cell counts or genes per cellA better understanding of advantages and disadvantages for each mapping algorithm might improve analysis results.
The social cerebellum: A large-scale investigation of functional and structural specificity and connectivity
Authors: Metoki Athanasia , Wang Yin , Olson Ingrid R. 
Published: February 2021

AbstractThe cerebellum has been traditionally disregarded in relation to non-motor functions, but recent findings indicate it may be involved in language, affective processing, and social functions. Mentalizing is the ability to infer mental states of others and this skill relies on a distributed network of brain regions. Here, we leveraged large-scale multimodal neuroimaging data to elucidate the structural and functional role of the cerebellum in mentalizing. We used functional activations to determine whether the cerebellum has a domain-general or domain-specific functional role, and effective connectivity and probabilistic tractography to map the cerebello-cerebral mentalizing network. We found that the cerebellum is organized in a domain-specific way and that there is a left cerebellar effective and structural lateralization, with more and stronger effective connections from the left cerebellar hemisphere to the right cerebral mentalizing areas, and greater cerebello-thalamo-cortical (CTC) and cortico-ponto-cerebellar (CPC) streamline counts from and to the left cerebellum. Our study provides novel insights to the network organization of the cerebellum, an overlooked brain structure, and mentalizing, one of humans’ most essential abilities to navigate the social world.
Effect of aging-related network changes on unimanual sensorimotor learning – a simultaneous EEG-fMRI study
Authors: Chettouf Sabrina , Triebkorn Paul , Daffertshofer Andreas , Ritter Petra 
Published: February 2021

AbstractSensorimotor coordination requires orchestrated network activity mediated by inter- and intra-hemispheric, excitatory and inhibitory neuronal interactions. Aging-related structural changes may alter these interactions. Disbalancing strength and timing of excitation and inhibition may limit motor performance. This is particularly true during motor coordination tasks that have to be learned through practice. To investigate this, we simultaneously acquired electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) in two groups of healthy adults (young N=13: 20-25y and elderly N=14: 59-70y), while they were practicing a unimanual motor task. Both groups learned the task during brain scanning, which was confirmed by a 24h follow-up retention test. On average, quality of performance of older participants stayed significantly below that of the younger ones. Accompanying decreases in motor-event-related EEG-source beta band power (β, 15-30 Hz) were lateralized in both groups towards the contralateral side, albeit more so in younger participants. In the latter, the mean β-power during motor learning in bilateral pre-motor cortex (PM1) was significantly higher than in the older group. Combined EEG/fMRI analysis revealed positive correlations between fMRI signals and source-reconstructed β-amplitude time courses in contralateral and ipsilateral M1, and negative correlations in bilateral PM1 for both groups. The β-positive fMRI response in bilateral M1 might be explained by an increased cross-talk between hemispheres during periods of pronounced β-activity. During learning, the Rolandic β-power relative to rest was higher in bilateral PM1 in younger participants, suggesting less task-related beta band desynchronization in this (better performing) group. We also found positive correlations between Rolandic β-amplitude and fMRI-BOLD in bilateral M1 and negative correlations bilateral in PM1. This indicates that increased β-amplitudes are associated with increased M1 “activity” (positive BOLD response) and decreased PM1 “activity” (negative BOLD response). Our results point at decreased pre-motor inhibitory inputs to M1 as possible source for increased interhemispheric crosstalk and an aging-related decline in motor performance.HighlightsSensorimotor coordination performance decreases with increasing age.During motor learning the β-power in pre-motor areas is reduced with age.EEG/fMRI points at less effective inhibitory inputs from PM1 to ipsilateral M1 in older adults.
Id4 is required for normal ependymal cell development
Authors: Rocamonde Brenda , Herranz-Pérez Vicente , Garcia-Verdugo Jose-Manuel , Huillard Emmanuelle 
Published: February 2021

AbstractEpendymal cells are radial glia-derived multiciliated cells lining the lateral ventricles of the brain and spinal cord. Correct development and coordinated cilia beating is essential for proper cerebrospinal fluid flow (CSF) and neurogenesis modulation. Dysfunctions of ependymal cells were associated with transcription factor deregulation. Here we provide evidence that the transcriptional regulator Id4 is involved in ependymal cell development and maturation. We observed thatId4-deficient mice display altered ependymal cytoarchitecture, decreased ependymal cell number, altered CSF flow and enlarged ventricles. Our findings open the way for a potential role of Id4 in ependymal cell development and/or motor cilia function.
Different evolutionary trends form the twilight zone of the bacterial pan-genome
Authors: Horesh Gal , Taylor-Brown Alyce , McGimpsey Stephanie , Lassalle Florent , Corander Jukka , Heinz Eva , Thomson Nicholas R. 
Published: February 2021

AbstractThe pan-genome is defined as the combined set of all genes in the gene pool of a species. Pan-genome analyses have been very useful in helping to understand different evolutionary dynamics of bacterial species: an open pan-genome often indicates a free-living lifestyle with metabolic versatility, while closed pan-genomes are linked to host-restricted, ecologically specialised bacteria. A detailed understanding of the species pan-genome has also been instrumental in tracking the phylodynamics of emerging drug resistance mechanisms and drug resistant pathogens. However, current approaches to analyse a species’ pan-genome do not take the species population structure into account, nor do they account for the uneven sampling of different lineages, as is commonplace due to over-sampling of clinically relevant representatives. Here we present the application of a population structure-aware approach for classifying genes in a pan-genome based on within-species distribution. We demonstrate our approach on a collection of 7,500E. coligenomes, one of the most-studied bacterial species used as a model for an open pan-genome. We reveal clearly distinct groups of genes, clustered by different underlying evolutionary dynamics, and provide a more biologically informed and accurate description of the species’ pan-genome.