bluuebunny/crossref_metadata_2025_split huggingface dataset:
EVALUATION OF THE ABBOTT SARS-COV-2 IG-G ASSAY
Authors: Lau CS , Hoo SP , Liang YL , Aw TC 
Published: June 2020

ABSTRACTIntroductionAntibodies to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can increase as soon as 10-13 days after infection. We describe our evaluation of the Abbott SARS-CoV-2 IgG assay on the Architect immunoassay analyser.MethodsWe assessed the precision, sensitivity, and specificity of the Abbott SARS-CoV-2 IgG assay in samples from polymerase chain reaction (PCR) positive patients and healthy healthcare workers. The manufacturer cut-off index (COI) of 1.4 was adopted to identify positive results. We examined the assay cross-reactivity with other viral antibodies (influenza/dengue/hepatitis C/hepatitis B) and rheumatoid factor (RF). The sample throughput of the Abbott assay was also assessed.ResultsThe Abbott assay showed excellent precision, with a CV of 3.4% for the negative control (COI = 0.06) and 1.6% for a high positive serum sample (COI = 8.6). Residual serum was available from 57 inpatients not initially suspected of having COVID-19, 29 of whom tested positive for SARS-CoV-2 IgG. The Abbott assay has a sensitivity of 90.9-100% when tested in 54 subjects ≥14 days post PCR positive, and a specificity of 100% (N = 358). There was no cross-reactivity with other viral antibodies (influenza/dengue/hepatitis C/hepatitis B) and RF. The Architect Abbott assay has a throughput of 100 samples in 70 minutes.ConclusionThe Abbott SARS-CoV-2 IgG assay shows excellent performance that is well within FDA and CDC guidelines when testing patients ≥14 days POS with little cross-reactivity from other viral antibodies. There is some evidence that SARS-CoV-2 IgG develops early in the disease process.IMPACT STATEMENTWith the current SARS-CoV-2 pandemic still ongoing, laboratories are hard pressed to introduce SARS-CoV-2 antibody testing to help as an indirect marker for infection to identify patients with prior infection/exposure. The Abbott SARS-CoV-2 IgG assay has excellent performance with good precision, specificity, and sensitivity ≥14 days after a positive SARS-CoV-2 PCR test, with a competitive throughput of 100 samples in 70 minutes. It shows no cross-reactivity with other viral antibodies (influenza/dengue/hepatitis B/hepatitis C) and rheumatoid factor. We have also found evidence of early antibody development in some patients before they tested positive on the SARS-CoV-2 PCR test.
Discovery of a Cellular Mechanism Regulating Transcriptional Noise
Authors: Desai Ravi V. , Hansen Maike M.K. , Martin Benjamin , Yu Chen , Ding Sheng , Thomson Matt , Weinberger Leor S. 
Published: June 2020

AbstractStochastic fluctuations in gene expression (‘noise’) are often considered detrimental but, in other fields, fluctuations are harnessed for benefit (e.g., ‘dither’ or amplification of thermal fluctuations to accelerate chemical reactions). Here, we find that DNA base-excision repair amplifies transcriptional noise, generating increased cellular plasticity and facilitating reprogramming. The DNA-repair protein Apex1 recognizes modified nucleoside substrates to amplify expression noise—while homeostatically maintaining mean levels of expression— for virtually all genes across the transcriptome. This noise amplification occurs for both naturally occurring base modifications and unnatural base analogs. Single-molecule imaging shows amplified noise originates from shorter, but more intense, transcriptional bursts that occur via increased DNA supercoiling which first impedes and then accelerates transcription, thereby maintaining mean levels. Strikingly, homeostatic noise amplification potentiates fate-conversion signals during cellular reprogramming. These data suggest a functional role for the observed occurrence of modified bases within DNA in embryonic development and disease.
Genome-wide association studies identify 137 loci for DNA methylation biomarkers of ageing
Authors: McCartney Daniel L. , Min Josine L. , Richmond Rebecca C. , Lu Ake T. , Sobczyk Maria K. , Davies Gail , Broer Linda , Guo Xiuqing , Jeong Ayoung , Jung Jeesun , Kasela Silva , Katrinli Seyma , Kuo Pei-Lun , Matias-Garcia Pamela R. , Mishra Pashupati P. , Nygaard Marianne , Palviainen Teemu , Patki Amit , Raffield Laura M. , Ratliff Scott M. , Richardson Tom G. , Robinson Oliver , Soerensen Mette , Sun Dianjianyi , Tsai Pei-Chien , van der Zee Matthijs D. , Walker Rosie M. , Wang Xiaochuan , Wang Yunzhang , Xia Rui , Xu Zongli , Yao Jie , Zhao Wei , Correa Adolfo , Boerwinkle Eric , Dugué Pierre-Antoine , Durda Peter , Elliott Hannah R , Gieger Christian ,   The Genetics of DNA Methylation Consortium, de Geus Eco J.C. , Harris Sarah E. , Hemani Gibran , Imboden Medea , Kähönen Mika , Kardia Sharon L.R. , Kresovich Jacob K. , Li Shengxu , Lunetta Kathryn L. , Mangino Massimo , Mason Dan , McIntosh Andrew M. , Mengel-From Jonas , Moore Ann Zenobia , Murabito Joanne M. ,   NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, Ollikainen Miina , Pankow James S. , Pedersen Nancy L. , Peters Annette , Polidoro Silvia , Porteous David J. , Raitakari Olli , Rich Stephen S. , Sandler Dale P. , Sillanpää Elina , Smith Alicia K , Southey Melissa C. , Strauch Konstantin , Tiwari Hemant , Tanaka Toshiko , Tillin Therese , Uitterlinden Andre G , Van Den Berg David J. , van Dongen Jenny , Wilson James G. , Wright John , Yet Idil , Arnett Donna , Bandinelli Stefania , Bell Jordana T. , Binder Alexandra M , Boomsma Dorret I , Chen Wei , Christensen Kaare , Conneely Karen N. , Elliott Paul , Ferrucci Luigi , Fornage Myriam , Hägg Sara , Hayward Caroline , Irvin Marguerite , Kaprio Jaakko , Lawlor Deborah A. , Lehtimäki Terho , Lohoff Falk W. , Milani Lili , Milne Roger L. , Probst-Hensch Nicole , Reiner Alex P. , Ritz Beate , Rotter Jerome I. , Smith Jennifer A. , Taylor Jack A. , van Meurs Joyce B.J. , Vineis Paolo , Waldenberger Melanie , Deary Ian J. , Relton Caroline L. , Horvath Steve , Marioni Riccardo E. 
Published: June 2020

AbstractBiological ageing estimators derived from DNA methylation (DNAm) data are heritable and correlate with morbidity and mortality. Leveraging DNAm and SNP data from >41,000 individuals, we identify 137 genome-wide significant loci (113 novel) from meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We report strong genetic correlations with longevity and lifestyle factors such as smoking, education, and obesity. Significant associations are observed in polygenic risk score analysis and to a lesser extent in Mendelian randomization analyses. This study illuminates the genetic architecture underlying epigenetic ageing and its shared genetic contributions with lifestyle factors and longevity.
Iron-meditated fungal starvation by lupine rhizosphere-associated and extremotolerantStreptomycessp. S29 desferrioxamine production
Authors: Jarmusch Scott A. , Lagos-Susaeta Diego , Diab Emtinan , Salazar Oriana , Asenjo Juan A. , Ebel Rainer , Jaspars Marcel 
Published: June 2020

ABSTRACTSiderophores are iron-chelating compounds that aid iron uptake, one of the key strategies for microorganisms to carve out ecological niches in microbially diverse environments. Desferrioxamines are the principal siderophores produced byStreptomycesspp. Their biosynthesis has been well studied and as a consequence, the chemical potential of the pathway continues to expand. With all of this in mind, our study aimed to explore extremotolerant and Lupine rhizosphere-derivedStreptomycessp. S29 for its potential antifungal capabilities. Cocultivation of isolate S29 was carried out withAspergillus nigerandBotrytis cinerea, both costly fungal phytopathogens in the wine industry, to simulate their interaction within the rhizosphere. The results indicate that not only isStreptomycessp. S29 extraordinary at producing hydroxamate siderophores but uses siderophore production as a means to ‘starve’ the fungi of iron. High resolution LC-MS/MS followed by GNPS molecular networking was used to observe the datasets for desferrioxamines and guided structure elucidation of new desferrioxamine analogues. Comparing the new chemistry, using tools like molecular networking and MS2LDA, with the known biosynthesis, we show that the chemical potential of the desferrioxamine pathway has further room for exploration.
A universal RT-qPCR assay for “One Health” detection of influenza A viruses
Authors: Nagy Alexander , Černíková Lenka , Kunteová Kateřina , Dirbáková Zuzana , Thomas Saumya S , Slomka Marek J , Dán Ádám , Varga Tünde , Máté Martina , Jiřincová Helena , Brown Ian H 
Published: June 2020

AbstractThe mutual dependence of human and animal health is central to the One Health initiative as an integrated strategy for infectious disease control and management. A crucial element of the One Health includes preparation and response to influenza A virus (IAV) threats at the human-animal interface. The IAVs are characterized by extensive genetic variability, they circulate among different hosts and establish host-specific lineages. The four main host reservoirs are: avian, swine, human and equine, with occasional transmission to other mammalian species. The host diversity is mirrored in the range of the RT-qPCR assays for IAV detection. Different assays are recommended by the responsible health authorities for generic IAV detection in birds, swine or humans. In order to unify IAV monitoring in different hosts and apply the One Health approach, we developed a single RT-qPCR assay for universal detection of all IAVs of all subtypes, species origin and global distribution. The assay design was centred on a highly conserved region of the IAV MP-segment identified by a comprehensive analysis of 99,353 sequences. The reaction parameters were effectively optimised with efficiency of 93-97% and LOD95%of approximately ten IAV templates per reaction. The assay showed high repeatability, reproducibility and robustness. The extensivein silicoevaluation demonstrated high inclusivity, i.e. perfect sequence match in the primers and probe binding regions, established as 94.6% for swine, 98.2% for avian and 100% for human H3N2, pandemic H1N1, as well as other IAV strains, resulting in an overall predicted detection rate of 99% on the analysed dataset. The theoretical predictions were confirmed and extensively validated by collaboration between six veterinary or human diagnostic laboratories on a total of 1970 specimens, of which 1455 were clinical and included a diverse panel of IAV strains.
Mapping genetic effects on cellular phenotypes with “cell villages”
Authors: Mitchell Jana M. , Nemesh James , Ghosh Sulagna , Handsaker Robert E. , Mello Curtis J. , Meyer Daniel , Raghunathan Kavya , de Rivera Heather , Tegtmeyer Matt , Hawes Derek , Neumann Anna , Nehme Ralda , Eggan Kevin , McCarroll Steven A. 
Published: June 2020

SummaryTens of thousands of genetic variants shape human phenotypes, mostly by unknown cellular mechanisms. Here we describe Census-seq, a way to measure cellular phenotypes in cells from many people simultaneously. Analogous to pooled CRISPR screens but for natural variation, Census-seq associates cellular phenotypes to donors’ genotypes by quantifying the presence of each donor’s DNA in cell “villages” before and after sorting or selection for cellular traits of interest. Census-seq enables population-scale cell-biological phenotyping with low cost and high internal control. We demonstrate Census-seq through investigation of genetic effects on the SMN protein whose deficiency underlies spinal muscular atrophy (SMA). Census-seq quantified and mapped effects of many common alleles on SMN protein levels and response to SMN-targeted therapeutics, including a common, cryptic non-responder allele. We provide tools enabling population-scale cell experiments and explain how Census-seq can be used to map genetic effects on diverse cell phenotypes.Abstract FigureHighlightsCensus-seq reveals how inherited genetic variation affects cell phenotypesGenetic analysis of cellular traits in cell villages of >100 donorsCharacterizing human alleles that shape SMN protein expression and drug responsesDevelopment of protocols and software to enable cellular population genetics
Hierarchical sparse coding of objects in deep convolutional neural networks
Authors: Liu Xingyu , Zhen Zonglei , Liu Jia 
Published: June 2020

AbstractRecently, deep convolutional neural networks (DCNNs) have attained human-level performances on challenging object recognition tasks owing to their complex internal representation. However, it remains unclear how objects are represented in DCNNs with an overwhelming number of features and non-linear operations. In parallel, the same question has been extensively studied in primates’ brain, and three types of coding schemes have been found: one object is coded by entire neuronal population (distributed coding), or by one single neuron (local coding), or by a subset of neuronal population (sparse coding). Here we asked whether DCNNs adopted any of these coding schemes to represent objects. Specifically, we used the population sparseness index, which is widely-used in neurophysiological studies on primates’ brain, to characterize the degree of sparseness at each layer in two representative DCNNs pretrained for object categorization, AlexNet and VGG11. We found that the sparse coding scheme was adopted at all layers of the DCNNs, and the degree of sparseness increased along the hierarchy. That is, the coding scheme shifted from distributed-like coding at lower layers to local-like coding at higher layers. Further, the degree of sparseness was positively correlated with DCNNs’ performance in object categorization, suggesting that the coding scheme was related to behavioral performance. Finally, with the lesion approach, we demonstrated that both external learning experiences and built-in gating operations were necessary to construct such a hierarchical coding scheme. In sum, our study provides direct evidence that DCNNs adopted a hierarchically-evolved sparse coding scheme as the biological brain does, suggesting an implementation-independent principle of representing a myriad of objects efficiently.
NGS-PrimerPlex: high-throughput primer design for multiplex polymerase chain reactions
Authors: Kechin Andrey , Borobova Viktoria , Boyarskikh Ulyana , Khrapov Evgeniy , Subbotin Sergey , Filipenko Maxim 
Published: June 2020

AbstractSummaryMultiplex PCR has multiple applications in molecular biology, including developing new targeted NGS-panels. We present NGS-PrimerPlex, an efficient and versatile command-line application that designs primers for different refined types of amplicon-based genome target enrichment. It supports nested and anchored multiplex PCR, redistribution among multiplex reactions of primers constructed earlier and extension of existing NGS-panels. The primer design process takes into consideration formation of secondary structures, non-target amplicons between all primers of a pool, primers and high-frequent genome SNPs overlapping. Moreover, users of NGS-PrimerPlex are free from manually defining input genome regions, because it can be done automatically from a list of genes or their parts like exon or codon numbers. Using the program, NGS-panel for sequencing theLRRK2gene coding regions was created, and 354 DNA samples were studied successfully with median coverage of 97.4% of target regions by at least 30 reads.Availability and implementationNGS-PrimerPlex is open-source and freely available athttps://github.com/aakechin/NGS-PrimerPlex/.Contactaa_kechin@niboch.nsc.ruSupplementary informationSupplementary data
Morpho-molecular diversity and evolutionary analyses suggest hidden life styles in Spumellaria (Radiolaria)
Authors: Sandin Miguel M. , Biard Tristan , Romac Sarah , O’Dogherty Luis , Suzuki Noritoshi , Not Fabrice 
Published: June 2020

AbstractSpumellaria (Radiolaria, Rhizaria) are holoplanktonic amoeboid protists, ubiquitous and abundant in the global ocean. Their silicified skeleton preserves very well in sediments displaying an excellent fossil record, from the early middle Cambrian (ca. 509-521 Ma), extremely valuable for paleo-environmental reconstruction studies. Spumellaria are tedious to maintain in laboratory conditions preventing an accurate perception of their extant diversity and ecology in today’s oceans, most of which being inferred from sediment records. This study represents an integrated and comprehensive classification of Spumellaria based on the combination of ribosomal taxonomic marker genes (rDNA) and morphological characteristics. In contrast to established taxonomic knowledge, we demonstrate that symmetry of the skeleton takes more importance than internal structures at high taxonomic rank classification. Such reconsideration allows gathering different morphologies with concentric structure and a spherical or radial symmetry believed to belong to other Radiolaria orders from the fossil record, as for some Entactinaria families. Results obtained in this study suggest the existence of new Spumellaria diversity at early diverging positions, in which a non-bearing skeleton organism lives within shelled ones. Using fossil calibrated molecular clock we estimated the origin of Spumellaria in the middle Cambrian (ca. 515 Ma), in agreement with the appearance of the first radiolarian representatives in the fossil record. The morpho-molecular and evolutionary framework established herein allows a direct connection between living specimens and fossil morphologies from the Cambrian, bringing both a standpoint for future molecular environmental surveys and a better understanding for paleo-environmental reconstruction studies.
RNA Atlas of Human Bacterial Pathogens Uncovers Stress Dynamics Linked to Infection
Authors: Avican Kemal , Aldahdooh Jehad , Togninalli Matteo , Tang Jing , Borgwardt Karsten M. , Rhen Mikael , Fällman Maria 
Published: June 2020

AbstractDespite being genetically diverse, bacterial pathogens can adapt to similar stressful environments in human host, but how this diversity allows them to achive this is yet not fully understood. Knowledge gained through comparative genomics is insufficient as it lacks the level of gene expression reflecting gene usage. To fill this gap, we investigated the transcriptome of 32 diverse bacterial pathogens under 11 host related stress conditions. We revealed that diverse bacterial pathogens have common responses to similar stresses to a certain extent but mostly employ their unique repertoire with intersections between different stress responses. We also identified universal stress responders which shed light on the nature of antimicrobial targets. In addition, we found that known and unknown putative novel ncRNAs comprised a significant proportion of the responses. All the data is collected in PATHOgenex atlas, providing ample opportunities to discover novel players critical for virulence and maintenance of infection.
AutoSpill: A method for calculating spillover coefficients to compensate or unmix high-parameter flow cytometry data
Authors: Roca Carlos P. , Burton Oliver T. , Prezzemolo Teresa , Whyte Carly E. , Halpert Richard , Kreft Łukasz , Collier James , Botzki Alexander , Spidlen Josef , Humblet-Baron Stéphanie , Liston Adrian 
Published: June 2020

AbstractCompensating in classical flow cytometry or unmixing in spectral systems is an unavoidable challenge in the data analysis of fluorescence-based flow cytometry. In both cases, spillover coefficients are estimated for each fluorophore using single-color controls. This approach has remained essentially unchanged since its inception, and is increasingly limited in its ability to deal with high-parameter flow cytometry. Here, we present AutoSpill, a novel approach for calculating spillover coefficients or spectral signatures of fluorophores. The approach combines automated gating of cells, calculation of an initial spillover matrix based on robust linear regression, and iterative refinement to reduce error. Moreover, autofluorescence can be compensated out, by processing it as an endogenous dye in an unstained control. AutoSpill uses single-color controls and is compatible with common flow cytometry software, but it differs in two key aspects from current methods: (1) it is much less demanding in the preparation of controls, as it does not require the presence of well-defined positive and negative populations, and (2) it does not require manual tuning of the spillover matrix, as the algorithm iteratively computes the tuning, producing an optimal compensation matrix. Another algorithm, AutoSpread, complements this approach, providing a robust estimate of the Spillover Spreading Matrix (SSM), while avoiding the need for well-defined positive and negative populations. Together, AutoSpill and AutoSpread provide a superior solution to the problem of fluorophore spillover, allowing simpler and more robust workflows in high-parameter flow cytometry.
Perversely expressed long noncoding RNAs can alter host response and viral proliferation in SARS-CoV-2 infection
Authors: Turjya Rafeed Rahman , Khan Md. Abdullah-Al-Kamran , Islam Abul Bashar Mir Md. Khademul 
Published: June 2020

AbstractBackgroundSince December 2019, the world is experiencing an unprecedented crisis due to a novel coronavirus, SARS-CoV-2. Owing to poor understanding of pathogenicity, the virus is eluding treatment and complicating recovery. Regulatory roles of long non-coding RNAs (lncRNAs) during viral infection and associated antagonism of host antiviral immune responses has become more evident in last decade. To elucidate possible functions of lncRNAs in the COVID-19 pathobiology, we have utilized RNA-seq dataset of SARS-CoV-2 infected lung epithelial cells.ResultsOur analyses uncover 21 differentially expressed lncRNAs whose functions are broadly involved in cell survival and regulation of gene expression. By network enrichment analysis we find that these lncRNAs can directly interact with differentially expressed protein-coding genesADAR, EDN1, KYNU, MALL, TLR2andYWHAG; and alsoAKAP8L, EXOSC5, GDF15, HECTD1, LARP4B, LARP7, MIPOL1, UPF1, MOV10andPRKAR2A, host genes that interact with SARS-CoV-2 proteins. These genes are involved in cellular signaling, metabolism, immune response and RNA homeostasis. Since lncRNAs have been known to sponge microRNAs and protect expression of upregulated genes, we also identified 9 microRNAs that are induced in viral infections; however, some lncRNAs are able to block their usual suppressive effect on overexpressed genes and consequently contribute to host defense and cell survival.ConclusionsOur investigation determines that deregulated lncRNAs in SARS-CoV-2 infection are involved in viral proliferation, cellular survival, and immune response, ultimately determining disease outcome and this information could drive the search for novel RNA therapeutics as a treatment option.