bluuebunny/crossref_metadata_2025_split huggingface dataset:
ChAlPred: A Web Server for Prediction of Allergenicity of Chemical Compounds
Authors: Sharma Neelam , Patiyal Sumeet , Dhall Anjali , Devi Naorem Leimarembi , Raghava Gajendra P. S. 
Published: May 2021

AbstractAllergy is the abrupt reaction of the immune system that may occur after the exposure with allergens like protein/peptide or chemical allergens. In past number of methods of have been developed for classifying the protein/peptide based allergen. To the best of our knowledge, there is no method to classify the allergenicity of chemical compound. Here, we have proposed a method named “ChAlPred”, which can be used to fill the gap for predicting the chemical compound that might cause allergy. In this study, we have obtained the dataset of 403 allergen and 1074 non-allergen chemical compounds and used 2D, 3D and FP descriptors to train, test and validate our prediction models. The fingerprint analysis of the dataset indicates that PubChemFP129 and GraphFP1014 are more frequent in the allergenic chemical compounds, whereas KRFP890 is highly present in non-allergenic chemical compounds. Our XGB based model achieved the AUC of 0.89 on validation dataset using 2D descriptors. RF based model has outperformed other classifiers using 3D descriptors (AUC = 0.85), FP descriptors (AUC = 0.92), combined descriptors (AUC = 0.93), and hybrid model (AUC = 0.92) on validation dataset. In addition, we have also reported some FDA-approved drugs like Cefuroxime, Spironolactone, and Tioconazole which can cause the allergic symptoms. A user user-friendly web server named “ChAlPred” has been developed to predict the chemical allergens. It can be easily accessed at https://webs.iiitd.edu.in/raghava/chalpred/.
Optimal spatial monitoring of populations described by reaction-diffusion models
Authors: Parisey Nicolas , Leclerc Melen , Adamczyk-Chauvat Katarzyna 
Published: May 2021

AbstractUsing spatialised population measurements and related geographic habitat data, it is quite feasible nowadays to derive parsimonious spatially explicit population models and to carry on their parameter estimation. To achieve such goal, reaction-diffusion models are fairly common in conservation biology and agricultural plant health where they are used, for example, for landscape planning or epidemiological surveillance. Unfortunately, if the mathematical methods and computational power are readily available, biological measurements are not. Despite the high throughput of some habitat related remote sensors, the experimental cost of biological measurements are, in our view, one of the worst bottleneck against a widespread usage of reaction-diffusion models. Hence, in this paper, we will recall some classical methods for optimal experimental design that we deem useful to spatial ecologist. Using two case studies, one in landscape ecology and one in conservation biology, we will show how to constructa prioriexperimental design minimizing variance of parameter estimates, enabling optimal experimental setup with pre and post hoc filtering for accommodating additional constraints.
Tools for accurate post hoc determination of marker location within whole-brain microscopy images
Authors: Tyson Adam L. , Vélez-Fort Mateo , Rousseau Charly V. , Cossell Lee , Tsitoura Chryssanthi , Obenhaus Horst A. , Claudi Federico , Lenzi Stephen C. , Branco Tiago , Margrie Troy W. 
Published: May 2021

AbstractTo interpret in vivo experiments designed to understand brain function, high-resolution whole-brain microscopy provides a means for post hoc determination of the location of implanted devices and recorded cells in three dimensional brain space that is a critical step for data interrogation. Here we have developed Python-based tools (brainreg and brainreg-segment) to accurately map, in a common coordinate space, the position of dye-labelled probe tracks and two-photon imaged cell populations expressing fluorescent protein. The precise location of probes and cells were validated using physiological recordings and human raters that indicate accuracy levels to less than 70µm. These flexible, open-source methodologies are expected to further evolve with need and to deliver the anatomical precision that is necessary for understanding the functional architecture of the brain.
recount3: summaries and queries for large-scale RNA-seq expression and splicing
Authors: Wilks Christopher , Zheng Shijie C. , Chen Feng Yong , Charles Rone , Solomon Brad , Ling Jonathan P. , Imada Eddie Luidy , Zhang David , Joseph Lance , Leek Jeffrey T. , Jaffe Andrew E. , Nellore Abhinav , Collado-Torres Leonardo , Hansen Kasper D. , Langmead Ben 
Published: May 2021

ABSTRACTWe present recount3, a resource consisting of over 750,000 publicly available human and mouse RNA sequencing (RNA-seq) samples uniformly processed by our new Monorail analysis pipeline. To facilitate access to the data, we provide the recount3 and snapcount R/Bioconductor packages as well as complementary web resources. Using these tools, data can be downloaded as study-level summaries or queried for specific exon-exon junctions, genes, samples, or other features. Monorail can be used to process local and/or private data, allowing results to be directly compared to any study in recount3. Taken together, our tools help biologists maximize the utility of publicly available RNA-seq data, especially to improve their understanding of newly collected data. recount3 is available from http://rna.recount.bio.
Silencing Doublesex expression triggers three-level pheromonal feminization in Nasonia males
Authors: Wang Yidong , Sun Weizhao , Fleischmann Sonja , Millar Jocelyn G. , Ruther Joachim , Verhulst Eveline C 
Published: May 2021

AbstractThe transcription factor Doublesex (Dsx) has a conserved function in controlling sexual morphological differences in insects, but our knowledge on its role in regulating sexual behavior is widely limited to Drosophila. Here, we show in the parasitoid wasp Nasonia vitripennis that males whose Dsx gene had been silenced by RNA interference (NvDsx-i) underwent a three-level pheromonal feminization: (1) NvDsx-i males were no longer able to attract females from a distance, owing to drastically reduced titers of the abdominal long-range sex pheromone. (2) NvDsx-i males were courted by wild-type males like females which correlated with a lower abundance of alkenes in their cuticular hydrocarbon (CHC) profiles. Supplementation of NvDsx-i male CHC profiles with realistic amounts of synthetic (Z)-9-hentriacontene (Z9C31), the most significantly reduced alkene in NvDsx-i males, interrupted courtship by wild-type conspecific males. Supplementation of female CHC profiles with Z9C31 reduced courtship and mating attempts by wild-type males. These results prove that Z9C31 is crucial for sex discrimination in Nasonia. (3) Nvdsx-i males were hampered in eliciting female receptivity during courtship and thus experienced severely reduced mating success, suggesting that they are unable to produce the hitherto unidentified oral aphrodisiac pheromone reported in N. vitripennis males. We conclude that Dsx is a multi-level key regulator of pheromone-mediated sexual communication in N. vitripennis. Silencing Dsx by RNA interference provides a new avenue for unraveling the molecular mechanisms underlying the pheromone-mediated sexual communication in insects.
A proteomics sample metadata representation for multiomics integration, and big data analysis
Authors: Dai Chengxin , Füllgrabe Anja , Pfeuffer Julianus , Solovyeva Elizaveta , Deng Jingwen , Moreno Pablo , Kamatchinathan Selvakumar , Kundu Deepti Jaiswal , George Nancy , Fexova Silvie , Grüning Björn , Föll Melanie Christine , Griss Johannes , Vaudel Marc , Audain Enrique , Locard-Paulet Marie , Turewicz Michael , Eisenacher Martin , Uszkoreit Julian , Van Den Bossche Tim , Schwämmle Veit , Webel Henry , Schulze Stefan , Bouyssié David , Jayaram Savita , Duggineni Vinay Kumar , Samaras Patroklos , Wilhelm Mathias , Choi Meena , Wang Mingxun , Kohlbacher Oliver , Brazma Alvis , Papatheodorou Irene , Bandeira Nuno , Deutsch Eric W. , Vizcaíno Juan Antonio , Bai Mingze , Sachsenberg Timo , Levitsky Lev , Perez-Riverol Yasset 
Published: May 2021

AbstractThe amount of public proteomics data is increasing at an extraordinary rate. Hundreds of datasets are submitted each month to ProteomeXchange repositories, representing many types of proteomics studies, focusing on different aspects such as quantitative experiments, post-translational modifications, protein-protein interactions, or subcellular localization, among many others. For every proteomics dataset, two levels of data are captured: the dataset description, and the data files (encoded in different file formats). Whereas the dataset description and data file formats are supported by all ProteomeXchange partner repositories, there is no standardized format to properly describe the sample metadata and their relationship with the dataset files in a way that fully allows their understanding or re-analysis. It is left to the user’s choice whether to provide or not an ad hoc document containing this information. Therefore, in many cases, understanding the study design and data requires going back to the associated publication. This can be tedious and may be restricted in the case of non-open access publications. In many cases, this problem limits the generalization and reuse of public proteomics data.Here we present a standard representation for sample metadata tailored to proteomics datasets produced by the HUPO Proteomics Standards Initiative and supported by ProteomeXchange resources. We repurposed the existing data format MAGE-TAB used routinely in the transcriptomics field to represent and annotate proteomics datasets. MAGETAB-Proteomics defines a set of annotation rules that the datasets submitted to ProteomeXchange should follow, ranging from sample properties to data analysis protocols. We also introduce a crowdsourcing project that enabled the manual curation of over 200 public datasets using MAGE-TAB-Proteomics. In addition, we describe an ecosystem of tools and libraries that were developed to validate and submit sample metadata-related information to ProteomeXchange. We expect that these tools will improve the reproducibility of published results and facilitate the reanalysis and integration of public proteomics datasets.
Vcflib and tools for processing the VCF variant call format
Authors: Garrison Erik , Kronenberg Zev N. , Dawson Eric T. , Pedersen Brent S. , Prins Pjotr 
Published: May 2021

AbstractSince its introduction in 2011 the variant call format (VCF) has been widely adopted for processing DNA and RNA variants in practically all population studies — as well as in somatic and germline mutation studies. VCF can present single nucleotide variants, multi-nucleotide variants, insertions and deletions, and simple structural variants called against a reference genome. Here we present over 125 useful and much used free and open source software tools and libraries, part of vcflib tools and bio-vcf. We also highlight cyvcf2, hts-nim and slivar tools. Application is typically in the comparison, filtering, normalisation, smoothing, annotation, statistics, visualisation and exporting of variants. Our tools run daily and invisibly in pipelines and countless shell scripts. Our tools are part of a wider bioinformatics ecosystem and we consider it very important to make these tools available as free and open source software to all bioinformaticians so they can be deployed through software distributions, such as Debian, GNU Guix and Bioconda. vcflib, for example, was installed over 40,000 times and bio-vcf was installed over 15,000 times through Bioconda by December 2020. We shortly discuss the design of VCF, lessons learnt, and how we can address more complex variation that can not easily be represented by the VCF format. All source code is published under free and open source software licenses and can be downloaded and installed from https://github.com/vcflib.Author summaryMost bioinformatics workflows deal with DNA/RNA variations that are typically represented in the variant call format (VCF) — a file format that describes mutations (SNP and MNP), insertions and deletions (INDEL) against a reference genome. Here we present a wide range of free and open source software tools that are used in biomedical sequencing workflows around the world today.
Distribution-free complex hypothesis testing for single-cell RNA-seq differential expression analysis
Authors: Gauthier Marine , Agniel Denis , Thiébaut Rodolphe , Hejblum Boris P. 
Published: May 2021

SummaryState-of-the-art methods for single-cell RNA sequencing (scRNA-seq) Differential Expression Analysis (DEA) often rely on strong distributional assumptions that are difficult to verify in practice. Furthermore, while the increasing complexity of clinical and biological single-cell studies calls for greater tool versatility, the majority of existing methods only tackle the comparison between two conditions. We propose a novel, distribution-free, and flexible approach to DEA for single-cell RNA-seq data. This new method, called ccdf, tests the association of each gene expression with one or many variables of interest (that can be either continuous or discrete), while potentially adjusting for additional covariates. To test such complex hypotheses,ccdfuses a conditional independence test relying on the conditional cumulative distribution function, estimated through multiple regressions. We provide the asymptotic distribution of theccdftest statistic as well as a permutation test (when the number of observed cells is not sufficiently large).ccdfsubstantially expands the possibilities for scRNA-seq DEA studies: it obtains good statistical performance in various simulation scenarios considering complex experimental designs (i.e.beyond the two condition comparison), while retaining competitive performance with state-of-the-art methods in a two-condition benchmark. We applyccdfto a large publicly available scRNA-seq dataset of 84,140 SARS-CoV-2 reactive CD8+ T cells, in order to identify the diffentially expressed genes across 3 groups of COVID-19 severity (mild, hospitalized, and ICU) while accounting for seven different cellular subpopulations.
ROS-Degradable Polythioketal Urethane Foam Dressings to Promote Porcine Skin Wound Repair
Authors: Patil Prarthana , Russo Katherine A. , McCune Joshua T. , Pollins Alonda C. , Cottam Matthew A. , Dollinger Bryan R. , Colazo Juan M. , Yu Fang , Martin John R. , Gupta Mukesh K. , Cardwell Nancy L. , Davidson Jeffrey M. , Thompson Callie M. , Barbul Adrian , Hasty Alyssa M. , Guelcher Scott A. , Duvall Craig L. 
Published: May 2021

AbstractImpaired skin healing and progression into chronic wounds is a prevalent and growing medical problem. Porous, resorbable biomaterials can be used as temporary substrates placed into skin defects to support cell infiltration, neo-tissue formation, and remodeling of nonhealing wounds. Naturally-derived biomaterials have promising healing benefits, but their low mechanical properties and exuberant costs limit their performance and use. Synthetic materials can be affordably manufactured and tuned across a broader range of physiochemical properties, but opportunities remain for tailoring them for ideal host immune and regenerative responses. Polyesters are the most clinically-tested class of synthetic biomaterials, but their hydrolysis releases acidic degradation products that can cause autocatalytic degradation processes that are poorly controlled and are not tied to cellular or other biologic activities. Here, we systemically explored a series of ROS-degradable polythioketal (PTK) urethane (UR) foams with varied hydrophilicity as an alternative class of synthetic biomaterials for wound healing. It was found that the most hydrophilic PTK- UR variant, which had 7 ethylene glycol (EG7) repeats flanking each side of each thioketal bond, had the highest ROS reactivity of the PTK-URs tested. In an in vivo porcine excisional skin wound healing model, hydrophilic EG7 PTK-UR foams more effectively promoted tissue integration, ECM deposition, and re- epithelialization of full-thickness skin wound compared to more hydrophobic PTK-UR variants. Resolution of type 1 inflammation and lower foreign body response to scaffold remnants was also observed for EG7 versus more hydrophobic PTK-UR scaffolds. Finally, porcine wound healing studies showed that EG7 PTK-UR foams had similar wound healing response to a collagen-based clinical gold standard product, Integra Bilayer Wound Matrix (BWM), while outperforming polyester UR foam-based NovoSorb Biodegradable Temporizing Matrix (BTM) with respect to increased ECM production, vascularization, and biomaterial-associated immune phenotype. In sum, PTK-UR foams warrant further development toward a new class of synthetic biomaterial foams for skin wound healing applications.
Repertoire of naturally acquired maternal antibodies transferred to infants for protection against shigellosis
Authors: Ndungo Esther , Andronescu Liana R. , Buchwald Andrea G , Lemme-Dumit Jose M. , Mawindo Patricia , Kapoor Neeraj , Fairman Jeff , Laufer Miriam K. , Pasetti Marcela F. 
Published: May 2021

AbstractShigellais the second leading cause of diarrheal diseases, accounting for >200,000 infections and >50,000 deaths in children under 5 years of age annually worldwide. The incidence ofShigella-induced diarrhea is relatively low during the first year of life and increases substantially, reaching its peak between 11 to 24 months of age. This epidemiological trend hints at an early protective immunity of maternal origin and an increase in disease incidence when maternally acquired immunity wanes. The magnitude, type, antigenic diversity, and antimicrobial activity of maternal antibodies transferred via placenta that can prevent shigellosis during early infancy are not known. To address this knowledge gap,Shigella-specific antibodies directed against the lipopolysaccharide (LPS) and virulence factors (IpaB, IpaC, IpaD, IpaH, and VirG), and antibody-mediated serum bactericidal (SBA) and opsonophagocytic killing antibody (OPKA) activity were measured in maternal and cord blood sera from a longitudinal cohort of mother-infant pairs living in rural Malawi. Protein-specific (very high levels) andShigellaLPS IgG were detected in maternal and cord blood sera; efficiency of placental transfer was 100% and 60%, respectively, and had preferential IgG subclass distribution (protein-specific IgG1 > LPS-specific IgG2). In contrast, SBA and OPKA activity in cord blood was substantially lower as compared to maternal serum and varied amongShigellaserotypes. LPS was identified as the primary target of SBA and OPKA activity. Maternal sera had remarkably elevatedShigella flexneri2a LPS IgM, indicative of recent exposure. Our study revealed a broad repertoire of maternally acquired antibodies in infants living in aShigella-endemic region and highlights the abundance of protein-specific antibodies and their likely contribution to disease prevention during the first months of life. These results contribute new knowledge on maternal infant immunity and target antigens that can inform the development of vaccines or therapeutics that can extend protection after maternally transferred immunity wanes.
Rapamycin induced hyperglycemia is associated with exacerbated age-related osteoarthritis
Authors: Minton Dennis M. , Elliehausen Christian J. , Javors Martin A. , Santangello Kelly S. , Konopka Adam R. 
Published: May 2021

AbstractBackgroundThe objective of this study was to determine if mechanistic target of rapamycin (mTOR) inhibition with or without AMP-activated protein kinase (AMPK) activation can protect against primary, age-related OA.DesignDunkin-Hartley guinea pigs develop mild primary OA pathology by 5-months of age that progresses to moderate OA by 8-months of age. At 5-months, guinea pigs sacrificed as young control (n=3) or were fed either a control diet (n=8), a diet enriched with the mTOR-inhibitor rapamycin (Rap, 14ppm, n=8), or Rap with the AMPK-activator metformin (Rap+Met, 1000ppm, n=8) for 12 weeks. Knee joints were evaluated by OARSI scoring, micro-computed tomography, and immunohistochemistry. Glenohumeral articular cartilage was collected for western blotting.ResultsRap and Rap+Met treated guinea pigs displayed lower body weight than control. Rap and Rap+Met inhibited articular cartilage mTORC1 but not mTORC2 signaling. Rap+Met, but not Rap alone, stimulated AMPK. Despite lower body weight and articular cartilage mTORC1 inhibition, Rap and Rap+Met treated guinea pigs had greater OA severity in the medial tibial plateau due to articular cartilage structural damage and/or proteoglycan loss. Rap and Rap+Met increased plasma glucose compared to control. Plasma glucose concentration was positively correlated with proteoglycan loss, suggesting hyperglycemic stress may have contributed to worsened OA.ConclusionsThis is the first study to show that Rap induced increase in plasma glucose was associated with greater OA severity. Further, articular cartilage mTORC1 inhibition and bodyweight reduction by dietary Rap and Rap+Met did not protect against primary OA during the prevailing hyperglycemia.
AMP-Kinase mediates regulation of glomerular volume and podocyte survival
Authors: Banu Khadija , Lin Qisheng , Basgen John M. , Planoutene Marina , Wei Chengguo , Reghuvaran Anand C. , Garzon Felipe , Garcia Aitor , Chun Nicholas , Cumpelik Arun , Shi Hongmei , Santaneusio Andrew , Zhang Weijia , Das Bhaskar , Salem Fadi , Li Li , Cantley Lloyd G , Ishibe Shuta , Kaufman Lewis , Lemley Kevin V. , Ni Zhaohui , He John C. , Murphy Barbara , Menon Madhav C. 
Published: May 2021

AbstractWe reported that Shroom3 knockdown, via Fyn inhibition, induced albuminuria with foot process effacement (FPE) without glomerulosclerosis (FSGS) or podocytopenia. Interestingly, knockdown mice had reduced podocyte volumes. Human minimal change disease, where podocyte Fyn inactivation was reported, also showed lower glomerular volumes than FSGS. We hypothesized that lower glomerular volume prevented the progression to podocytopenia. To test this hypothesis, we utilized unilateral- and 5/6thnephrectomy models in Shroom3 knockdown mice. Knockdown mice exhibited lower glomerular volume, and less glomerular and podocyte hypertrophy after nephrectomy. FYN-knockdown podocytes had similar reductions in podocyte volume, implying Fyn was downstream of Shroom3. Using SHROOM3- or FYN-knockdown, we confirmed reduced podocyte protein content, along with significantly increased phosphorylated AMP-kinase, a negative regulator of anabolism. AMP-Kinase activation resulted from increased cytoplasmic redistribution of LKB1 in podocytes. Inhibition of AMP-Kinase abolished the reduction in glomerular volume and induced podocytopenia in mice with FPE, suggesting a protective role for AMP-Kinase activation. In agreement with this, treatment of glomerular injury models with AMP-Kinase activators restricted glomerular volume, podocytopenia and progression to FSGS. In summary, we demonstrate the important role of AMP-Kinase in glomerular volume regulation and podocyte survival. Our data suggest that AMP-Kinase activation adaptively regulates glomerular volume to prevent podocytopenia in the context of podocyte injury.