bluuebunny/crossref_metadata_2025_split huggingface dataset:
HiCHub: A Network-Based Approach to Identify Domains of Differential Interactions from 3D Genome Data
Authors: Li Xiang , Yuan Shuang , Zhu Shaoqi , Xue Hai-Hui , Peng Weiqun 
Published: April 2022

AbstractChromatin architecture is important for gene regulation. Existing algorithms for the identification of interactions changes focus on loops between focal loci. Here we develop a network-based algorithm HiCHub to detect chromatin interaction changes at larger scales. It identifies clusters of genomic elements in physical proximity in one state that exhibit concurrent decreases in interaction among them in the opposite state. The hubs exhibit concordant changes in chromatin state and expression changes, supporting their biological significance. HiCHub works well with data of limited sequencing coverage and facilitates the integration of the one-dimensional epigenetic landscape onto the chromatin architecture. HiCHub provides an approach for finding extended architectural changes and contributes to the connection with transcriptional output. HiCHub is freely available at https://github.com/WeiqunPengLab/HiCHub.
Structural dynamics of Zika Virus NS1 via a reductionist approach reveal the disordered nature of its beta roll domain in isolation
Authors: Kapuganti Shivani Krishna , Kumar Prateek , Giri Rajanish 
Published: April 2022

AbstractFlavivirus Non-structural 1 (NS1) protein performs multiple functions such as host immune evasion, interaction with complement system factors, membrane rearrangement, etc. Therefore, it is highly plausible that significant structural and folding dynamics of NS1 might play a role in its multifunctionality. The dimeric structures of NS1 of multiple flaviviruses, including Zika virus (ZIKV), are available. However, its domain-wise dynamics perspective has not been explored so far. Therefore, it is of utmost importance to understand the structural conformations of NS1 and its domains in isolation, possibly highlighting the implications on the overall NS1 protein dynamics. Here, we have employed extensively long molecular dynamic (MD) simulations to understand the role of monomer, dimer, and a reductionist approach in understanding the dynamics of the three structural domains (i.e., β- roll, wing, and β-ladder) in isolation. Further, we experimentally validated our findings using CD spectroscopy and confirmed the intrinsically disordered behavior of NS1 β-roll in isolation and lipid mimetic environments. We also found that the β-ladder domain is highly flexible during long simulations. Therefore, we believe this study may have implications for significant dynamics played by NS1 protein, specifically during oligomerization of NS1.Graphical AbstractSchematic representation of the ZIKV NS1 protein and the models that we have used in this study.
Plant-on-Chip: core morphogenesis processes in the tiny plantWolffia australiana
Authors: Li Feng , Yang Jing-Jing , Sun Zong-Yi , Wang Lei , Qi Le-Yao , Sina A , Liu Yi-Qun , Zhang Hong-Mei , Dang Lei-Fan , Wang Shu-Jing , Luo Chun-Xiong , Nian Wei-Feng , O’Conner Seth , Ju Long-Zhen , Quan Wei-Peng , Li Xiao-Kang , Wang Chao , Wang De-Peng , You Han-Li , Cheng Zhu-Kuan , Yan Jia , Tang Fu-Chou , Yang De-Chang , Xia Chu-Wei , Gao Ge , Wang Yan , Zhang Bao-Cai , Zhou Yi-Hua , Guo Xing , Xiang Sun-Huan , Liu Huan , Peng Tian-Bo , Su Xiao-Dong , Chen Yong , Ouyang Qi , Wang Dong-Hui , Zhang Da-Ming , Xu Zhi-Hong , Hou Hong-Wei , Bai Shu-Nong , Li Ling 
Published: April 2022

AbstractA plant can be thought of as a colony comprising numerous growth buds, each developing to its own rhythm. Such lack of synchrony impedes efforts to describe core principles of plant morphogenesis, dissect the underlying mechanisms, and identify regulators. Here, we use the tiniest known angiosperm to overcome this challenge and provide an ideal model system for plant morphogenesis. We present a detailed morphological description of the monocotWolffia australiana, as well as high-quality genome information. Further, we developed the Plant-on-Chip culture system and demonstrate the application of advanced technologies such as snRNA-seq, protein structure prediction, and gene editing. We provide proof-of-concept examples that illustrate howW. australianacan open a new horizon for deciphering the core regulatory mechanisms of plant morphogenesis.SignificanceWhat is the core morphogenetic process in angiosperms, a plant like a tree indeterminately growing, or a bud sequentially generating limited types of organs?Wolffia australiana, one of the smallest angiosperms in the world may help to make a distinction. Wolffia plantlet constitutes of only three organs that are indispensable to complete life cycle: one leaf, one stamen and one gynoecium. Before the growth tip is induced to flower, it keeps branching from the leaf axil and the branches separate from the main plantlet. Here we present a high-quality genome ofW. australiana, detailed morphological description, a Plant-on-Chip cultural system, and some principle-proof experiments, demonstrating thatW. australianais a promising model system for deciphering core developmental program in angiosperms.
Gene editing is suitable to treat GM1 Gangliosidosis: a proof-of-concept study
Authors: Leclerc Delphine , Goujon Louise , Jaillard Sylvie , Nouyou Bénédicte , Cluzeau Laurence , Damaj Léna , Dubourg Christèle , Etcheverry Amandine , Levade Thierry , Froissart Roseline , Dréano Stéphane , Guillory Xavier , Eriksson Leif A , Launay Erika , Mouriaux Frédéric , Belaud-Rotureau Marc-Antoine , Odent Sylvie , Gilot David 
Published: April 2022

AbstractGanglioside-monosialic acid (GM1) gangliosidosis, a rare autosomal recessive disorder, is frequently caused by deleterious single nucleotide variants (SNVs) in GLB1 gene. These variants result in reduced β-galactosidase (β-gal) activity, leading to neurodegeneration associated with premature death. Currently, no effective therapy for GM1 gangliosidosis is available. Three ongoing clinical trials aim to deliver a functional copy of the GLB1 gene to stop disease progression. Here, we show that 41% of GLB1 pathogenic SNVs might be cured by adenine base editors (ABEs). Our results demonstrate that ABE efficiently corrects the pathogenic allele in patient-derived fibroblasts, restoring a therapeutic level of β-gal activity. Unbiased off-target DNA analysis did not detect off-target editing activity in treated patient’s cells except a bystander edit without consequences on β-gal activity. Altogether our results suggest that gene editing is an alternative strategy to cure GM1 gangliosidosis, by correcting the root cause of disease and avoiding repetitive adeno-associated virus injections.
Uncovering the “ZIP code” for bZIP dimers reveals novel motifs, regulatory rules and one billion years of cis-element evolution
Authors: Li Miaomiao , Lin Wanru , Hinckley Will , Yao Tao , Muchero Wellington , Chen Jin-Gui , Huang S. Carol 
Published: April 2022

AbstractMany eukaryotic transcription factors (TF) form homodimer or heterodimer complexes to regulate gene expression. For example, dimerization properties of the basic leucine zipper (bZIP) family play a critical role in regulating the unique biological functions in all eukaryotes. However, the molecular mechanism underlying the binding sequence and functional specificity of homo- versus heterodimers remains elusive. To fill this gap, we developed a double DNA Affinity Purification sequencing (dDAP-seq) technique that maps heterodimer DNA binding sites in an endogenous genome context. Our genome-wide binding profiles of twenty pairs of C/S1 bZIP heterodimers and S1 homodimers in Arabidopsis revealed that heterodimerization significantly expands the DNA binding preferences of bZIP TFs. Analysis of the heterodimer target genes in stress response and development suggest heterodimerization gives rise to regulatory responses that are distinct from the homodimers. In addition to the classic ACGT elements recognized by plant bZIPs, we found that the C/S1 heterodimers bound to motifs that might share an origin with the GCN4 cis-elements in yeast that diverged from plants more than one billion years ago. Importantly, heterodimer binding specificities can be distinguished by their relative preference for ACGT motifs versus GCN4-related motifs. More broadly, our study demonstrates the potential of dDAP-seq in deciphering the DNA binding specificities of interacting TFs that are key for combinatorial gene regulation.
Structure-based learning to model complex protein-DNA interactions and transcription-factor co-operativity incis-regulatory elements
Authors: Fornes O , Meseguer A , Aguirre-Plans J , Gohl P , Bota PM , Molina-Fernández R , Bonet J , Hernandez AC , Pegenaute F , Gallego O , Fernandez-Fuentes N , Oliva B 
Published: April 2022

ABSTRACTTranscription factor (TF) binding is a key component of genomic regulation. There are numerous high-throughput experimental methods to characterize TF-DNA binding specificities. Their application, however, is both laborious and expensive, which makes profiling all TFs challenging. For instance, the binding preferences of ~25% human TFs remain unknown; they neither have been determined experimentally nor inferred computationally. We introduce a structure-based learning approach to predict the binding preferences of TFs and the automated modelling of TF regulatory complexes. We show the advantage of using our approach over the state-of-art nearest-neighbor prediction in the limits of remote homology. Starting from a TF sequence or structure, we predict binding preferences in the form of motifs that are then used to scan a DNA sequence for occurrences. The best matches are either profiled with a binding score or collected for their subsequent modeling into a higher-order regulatory complex with DNA. Cooperativity is modelled by: i) the co-localization of TFs; and ii) the structural modeling of protein-protein interactions between TFs and with co-factors. As case examples, we apply our approach to automatically model the interferon-β enhanceosome and the pioneering complex of OCT4, SOX2 and SOX11 with a nucleosome, which are compared with the experimentally known structures.
Development of a high-density 665 K SNP array for rainbow trout genome-wide genotyping
Authors: Bernard Maria , Dehaullon Audrey , Gao Guangtu , Paul Katy , Lagarde Henri , Charles Mathieu , Prchal Martin , Danon Jeanne , Jaffrelo Lydia , Poncet Charles , Patrice Pierre , Haffray Pierrick , Quillet Edwige , Dupont-Nivet Mathilde , Palti Yniv , Lallias Delphine , Phocas Florence 
Published: April 2022

AbstractSingle nucleotide polymorphism (SNP) arrays, also named « SNP chips », enable very large numbers of individuals to be genotyped at a targeted set of thousands of genome-wide identified markers. We used preexisting variant datasets from USDA, a French commercial line and 30X-coverage whole genome sequencing of INRAE isogenic lines to develop an Affymetrix 665 K SNP array (HD chip) for rainbow trout. In total, we identified 32,372,492 SNPs that were polymorphic in the USDA or INRAE databases. A subset of identified SNPs were selected for inclusion on the chip, prioritizing SNPs whose flanking sequence uniquely aligned to the Swanson reference genome, with homogenous repartition over the genome and the highest Minimum Allele Frequency in both USDA and French databases. Of the 664,531 SNPs which passed the Affymetrix quality filters and were manufactured on the HD chip, 65.3% and 60.9% passed filtering metrics and were polymorphic in two other distinct French commercial populations in which, respectively, 288 and 175 sampled fish were genotyped. Only 576,118 SNPs mapped uniquely on both Swanson and Arlee reference genomes, and 12,071 SNPs did not map at all on the Arlee reference genome. Among those 576,118 SNPs, 38,948 SNPs were kept from the commercially available medium-density 57K SNP chip. We demonstrate the utility of the HD chip by describing the high rates of linkage disequilibrium at 2 kb to 10 kb in the rainbow trout genome in comparison to the linkage disequilibrium observed at 50 kb to 100 kb which are usual distances between markers of the medium-density chip.
MetaPhage: an automated pipeline for analyzing, annotating, and classifying bacteriophages in metagenomics sequencing data
Authors: Pandolfo Mattia , Telatin Andrea , Lazzari Gioele , Adriaenssens Evelien M. , Vitulo Nicola 
Published: April 2022

AbstractIn the last decades, a great interest has emerged in the study and characterisation of the microbiota, especially the human gut microbiota, demonstrating that commensal microorganisms play a pivotal role in normal anatomical development and physiological function of the human body. To better understand the complex bacterial dynamics that characterize different environments, bacteriophage predation and gene transfer need to be considered as well, as they are important factors that may contribute to controlling the density, diversity, and network interactions among bacterial communities. To date, a variety of bacteriophage identification tools have been developed, differing on phage mining strategies, input files requested and results produced; however, new users approaching the bacteriophage analysis might struggle in untangling the variety of methods and comparing the different results produced. Here we present MetaPhage, a comprehensive reads-to-report pipeline that streamlines the use of multiple miners and generates an exhaustive report to both summarize and visualize the key findings and to enable further exploration of specific results with interactive filterable tables. The pipeline is implemented in Nextflow, a widely adopted workflow manager, that enables an optimized parallelization of the tasks on different premises, from local server to the cloud, and ensures reproducible results using containerized packages. MetaPhage is designed to allow scalability, reproducibility and to be easily expanded with new miners and methods, in a field that is constantly expanding. MetaPhage is freely available under a GPL-3.0 license at https://github.com/MattiaPandolfoVR/MetaPhage.
Multi-marker DNA metabarcoding detects suites of environmental gradients from an urban harbour
Authors: Robinson Chloe V. , Porter Teresita M. , McGee Katie M. , McCusker Megan , Wright Michael T.G. , Hajibabaei Mehrdad 
Published: April 2022

AbstractThere is increasing need for biodiversity monitoring, especially in places where potential anthropogenic disturbance may significantly impact ecosystem health. We employed a combination of traditional morphological and bulk macroinvertebrate metabarcoding analyses to benthic samples collected from Toronto Harbour (Ontario, Canada) to compare taxonomic and functional diversity of macroinvertebrates and their responses to environmental gradients. At the species rank, sites assessed using COI metabarcoding showed more variation than sites assessed using morphological methods. Depending on the assessment method, we detected gradients in magnesium (morphological taxa), ammonia (morphological taxa, COI sequence variants), pH (18S sequence variants) as well as gradients in contaminants such as metals (COI & 18S sequence variants) and organochlorines (COI sequence variants). Observed responses to contaminants such as aromatic hydrocarbons and metals align with known patchy distributions in harbour sediments. We determined that the morphological approach may limit the detection of macroinvertebrate responses to lake environmental conditions due to the effort needed to obtain fine level taxonomic assignments necessary to investigate responses. DNA metabarcoding, however, need not be limited to macroinvertebrates, can be automated, and taxonomic assignments are associated with a certain level of accuracy from sequence variants to named taxonomic groups. The capacity to detect change using a scalable approach such as metabarcoding is critical for addressing challenges associated with biodiversity monitoring and ecological investigations.
An atlas of genetic scores to predict multi-omic traits
Authors: Xu Yu , Ritchie Scott C. , Liang Yujian , Timmers Paul R. H. J. , Pietzner Maik , Lannelongue Loïc , Lambert Samuel A. , Tahir Usman A. , May-Wilson Sebastian , Johansson Åsa , Surendran Praveen , Nath Artika P , Persyn Elodie , Peters James E. , Oliver-Williams Clare , Deng Shuliang , Prins Bram , Foguet Carles , Luan Jian’an , Bomba Lorenzo , Soranzo Nicole , Angelantonio Emanuele Di , Pirastu Nicola , Tai E Shyong , van Dam Rob M , Davenport Emma E , Paul Dirk S. , Yau Christopher , Gerszten Robert E. , Mälarstig Anders , Danesh John , Sim Xueling , Langenberg Claudia , Wilson James F. , Butterworth Adam S. , Inouye Michael 
Published: April 2022

AbstractGenetically predicted levels of multi-omic traits can uncover the molecular underpinnings of common phenotypes in a highly efficient manner. Here, we utilised a large cohort (INTERVAL; N=50,000 participants) with extensive multi-omic data for plasma proteomics (SomaScan, N=3,175; Olink, N=4,822), plasma metabolomics (Metabolon HD4, N=8,153), serum metabolomics (Nightingale, N=37,359), and whole blood Illumina RNA sequencing (N=4,136). We used machine learning to train genetic scores for 17,227 molecular traits, including 10,521 which reached Bonferroni-adjusted significance. We evaluated genetic score performances in external validation across European, Asian and African American ancestries, and assessed their longitudinal stability within diverse individuals. We demonstrated the utility of these multi-omic genetic scores by quantifying the genetic control of biological pathways and by generating a synthetic multi-omic dataset of UK Biobank to identify disease associations using a phenome-wide scan. Finally, we developed a portal (OmicsPred.org) to facilitate public access to all genetic scores and validation results as well as to serve as a platform for future extensions and enhancements of multi-omic genetic scores.
CD200R1 promotes IL-17 production by ILC3s, by enhancing STAT3 activation
Authors: Linley Holly , Ogden Alice , Jaigirdar Shafqat , Buckingham Lucy , Cox Joshua , Priestley Megan , Saunders Amy 
Published: April 2022

AbstractPsoriasis is a common chronic inflammatory skin disease with no cure. It is driven by the IL-23/IL-17A axis and TH17 cells but, recently group 3 innate lymphoid cells (ILC3s) have also been implicated. However, the development, and factors regulating the activity of ILC3s remain incompletely understood.Immune regulatory pathways are particularly important at barrier sites such as the skin, gut and lung, which are exposed to environmental substances and microbes. CD200R1 is an immune regulatory cell surface receptor which inhibits proinflammatory cytokine production in myeloid cells. CD200R1 is also highly expressed on ILCs, where its function remains largely unexplored. We previously observed reduced CD200R1 signalling in psoriasis skin, suggesting that dysregulation may promote disease. Here we show that contrary to this, psoriasis models are less severe in CD200R1-deficient mice due to reduced IL-17 production. Here we uncover a key cell-intrinsic role for CD200R1 in promoting IL-23-driven IL-17A production by ILC3s, by promoting STAT3 activation. CD200R1 is expressed on ILC precursors and is particularly high on neonatal ILC3s, suggesting CD200R1 may function during ILC development. Therefore, CD200R1 is required on ILC3s, potentially during their development, to promote IL-23-stimulated STAT3 activation triggering optimal IL-17 production.
SOAR elucidates disease mechanisms and empowers drug discovery through spatial transcriptomics
Authors: Li Yiming , Dennis Saya , Hutch Meghan R. , Ding Yanyi , Zhou Yadi , Li Yawei , Pillai Maalavika , Ghotbaldini Sanaz , Garcia Mario Alberto , Broad Mia S. , Mao Chengsheng , Cheng Feixiong , Zeng Zexian , Luo Yuan 
Published: April 2022

AbstractSpatial transcriptomics provides researchers with a better understanding of gene expression within the tissue context. Although large volumes of spatial transcriptomics data have been generated, the lack of systematic curation and analysis makes data reuse challenging. Herein, we present Spatial transcriptOmics Analysis Resource (SOAR), a resource with an extensive, systematically compiled collection of spatial transcriptomics data across tissues, organs, and pathological conditions. SOAR is a comprehensive database with uniformly processed and annotated samples, facilitating future benchmark studies and method development. SOAR also offers multi-pronged analysis capability, including an integrative approach toward drug discovery that allows for efficient exploration of novel and targeted therapeutic uses for existing compounds.
(A)symmetric interaction between house prices, stock market and exchange rates using linear and nonlinear approach: the case of Iran
Authors: Mahmoudinia Davoud , Mostolizadeh Seyed Mohammad 
Published: April 2022

PurposeThe purpose of this study was to investigate the dynamic interactive link between housing prices, stock market price and effective exchange rate in the Iranian economy for a monthly period from April, 2004, to March, 2019. In addition, for a more accurate analysis, three control and determinates variables including real interest rate, real GDP and FDI have been added to the base model.Design/methodology/approachFor this purpose, we will consider this issue by developing the study of Lean & Smyth (2014), Ali & Zaman (2017) and Coskun et al (2017) in the framework of ADRL and NARDL models. Also, this study analyzed the asymmetric/non-linear impact of stock market indexes and effective exchange rate on Iran’s housing inflation. Asymmetries imply to both positive and negative changes in the variables.FindingsThe results obtained from the ADRL and NARDL models suggest that the existence of cointegration relationship between housing market price and its determinants. From linear model, we found that the exchange rate and stock market price have a positive effect on the real estate inflation in the short run; this relationship is also confirmed in the long run. Other empirical results indicate that the GDP stimulates housing price in both long and short run cases, while FDI and real interest rate have an opposite effect. In addition, the results provided by the asymmetric model lead to the rejection of the null hypothesis of no co-integration between the variables. In addition, we found that the effect of stock price in the short and long term are asymmetric and there also is an asymmetric long-run effect of real exchange rate on the real estate price.Originality/valueFinally, to analyze the sensitivity, we entered two explanatory variables of inflation and money supply to the baseline equation. The finding represented that in both linear and nonlinear framework, a positive correlation between these two variables with housing prices have been proved.
Benefits on productivity indicators after quality management implementation: evidence in the dairy industry
Authors: Ruales Guzmán Bertha Viviana , Castellanos Domínguez Oscar Fernando 
Published: April 2022

PurposeThis study aims to address two objectives: to analyse how the benefits of quality management (QM) are perceived on specific productivity indicators of the Colombian dairy industry and to analyse the degree of QM implementation.Design/methodology/approachThe methodology used was a multiple case study and involved four companies in the Colombian dairy industry. The study variables were 32 QM practices and 7 productivity indicators. Data collection instruments were in-depth interviews and checklists.FindingsFindings revealed that all productivity indicators exhibit changes after QM implementation. In addition, cases approaching ISO 9001 have the highest number of practices implemented, as well as evidence of control of all productivity indicators, which allows them to perceive greater benefits.Originality/valueThis research generates novel findings that contribute to the consolidation of theory by analysing changes in specific productivity indicators of the dairy industry after the QM implementation. At the same time, it provides valuable and useful information for managers, practitioners and policymakers.