bluuebunny/crossref_metadata_2025_split huggingface dataset:
Haplocheck: Phylogeny-based Contamination Detection in Mitochondrial and Whole-Genome Sequencing Studies
Authors: Weissensteiner Hansi , Forer Lukas , Fendt Liane , Kheirkhah Azin , Salas Antonio , Kronenberg Florian , Schoenherr Sebastian 
Published: May 2020

AbstractWithin-species contamination is a major issue in sequencing studies, especially for mitochondrial studies. Contamination can be detected by analysing the nuclear genome or by inspecting the heteroplasmic sites in the mitochondrial genome. Existing methods using the nuclear genome are computationally expensive, and no suitable tool for detecting contamination in large-scale mitochondrial datasets is available. Here we present haplocheck, a tool that requires only the mitochondrial genome to detect contamination in both mitochondrial and whole-genome sequencing studies. Haplocheck is able to distinguish between contaminated and real heteroplasmic sites using the mitochondrial phylogeny. By applying haplocheck to the 1000 Genomes Project data, we show (1) high concordance in contamination estimates between mitochondrial and nuclear DNA and (2) quantify the impact of mitochondrial copy numbers on the mitochondrial based contamination results. Haplocheck complements leading nuclear DNA based contamination tools, and can therefore be used as a proxy tool in nuclear genome studies.Haplocheck is available both as a command-line tool athttps://github.com/genepi/haplocheckand as a cloud web-service producing interactive reports that facilitates the navigation through the phylogeny of contaminated samples.
Epigenetic regulator miRNA pattern differences among SARS-CoV, SARS-CoV-2 and SARS-CoV-2 world-wide isolates delineated the mystery behind the epic pathogenicity and distinct clinical characteristics of pandemic COVID-19
Authors: Khan Md. Abdullah-Al-Kamran , Sany Md. Rabi Us , Islam Md. Shafiqul , Mehebub Md. Saheb , Khademul Islam Abul Bashar Mir Md. 
Published: May 2020

AbstractDetailed molecular mechanism of SARS-CoV-2 pathogenesis is still elusive to address its deadlier nature and to design effective theraputics. Here, we present our study elucidating the interplay between the SARS-CoV and SARS-CoV-2 viruses’; and host’s miRNAs, an epigenetic regulator, as a mode of pathogenesis, and enlightened how the SARS-CoV and SARS-CoV-2 infections differ in terms of their miRNA mediated interactions with host and its implications in the disease complexity. We have utilized computational approaches to predict potential host and viral miRNAs, and their possible roles in different important functional pathways. We have identified several putative host antiviral miRNAs that can target the SARS viruses, and also SARS viruses’ encoded miRNAs targeting host genes.In silicopredicted targets were also integrated with SARS infected human cells microarray and RNA-seq gene expression data. Comparison of the host miRNA binding profiles on 67 different SARS-CoV-2 genomes from 24 different countries with respective country’s normalized death count surprisingly uncovered some miRNA clusters which are associated with increased death rates. We have found that induced cellular miRNAs can be both a boon and a bane to the host immunity, as they have possible roles in neutralizing the viral threat, parallelly, they can also function as proviral factors. On the other hand, from over representation analysis, interestingly our study revealed that although both SARS-CoV and SARS-CoV-2 viral miRNAs could target broad immune signaling pathways; only some of the SARS-CoV-2 miRNAs are found to uniquely target some immune signaling pathways like-autophagy, IFN-I signaling etc, which might suggest their immune-escape mechanisms for prolonged latency inside some hosts without any symptoms of COVID-19. Further, SARS-CoV-2 can modulate several important cellular pathways which might lead to the increased anomalies in patients with comorbidities like-cardiovascular diseases, diabetes, breathing complications, etc. This might suggest that miRNAs can be a key epigenetic modulator behind the overcomplications amongst the COVID-19 patients. Our results support that miRNAs of host and SARS-CoV-2 can indeed play a role in the pathogenesis which can be further concluded with more experiments. These results will also be useful in designing RNA therapeutics to alleviate the complications from COVID-19.
Identification of 370 genetic loci for age at first sex and birth linked to externalising behaviour
Authors: Mills Melinda C. , Tropf Felix C. , Brazel David M. , van Zuydam Natalie , Vaez Ahmad ,   eQTLGen Consortium, BIOS Consortium, Pers Tune H. , Snieder Harold , Perry John R.B. , Ong Ken K. , den Hoed Marcel , Barban Nicola , Day Felix R. 
Published: May 2020

AbstractAge at first sexual intercourse (AFS) and age at first birth (AFB) have implications for health and evolutionary fitness. In the largest genome-wide association study to date (AFS, N=387,338; AFB, N=542,901), we identify 370 independent signals, 11 sex-specific, with a 5-6% polygenic score (PGS) prediction. Heritability of AFB shifted from 9% [CI=4-14] for women born in 1940 to 22% [CI=19-25] in 1965. Signals are driven by the genetics of reproductive biology and externalising behaviour, with key genes related to follicle stimulating hormone (FSHB), implantation (ESR1), infertility, and spermatid differentiation. Polycystic Ovarian Syndrome leads to later AFB, linking with infertility. Late AFB is protective against later-life disease and associated with parental longevity. Higher childhood socioeconomic circumstances and those in the highest PGS decile (90%+) experience markedly later reproductive onset. Results are relevant for improving teenage and late-life health, for understanding longevity, and guiding experimentation into mechanisms of infertility.
Dynamic patterns of YAP1 expression and cellular localization in the developing and injured utricle
Authors: Borse Vikrant , Barton Matthew , Arndt Harry , Kaur Tejbeer , Warchol Mark E. 
Published: May 2020

AbstractThe Hippo pathway is an evolutionarily conserved signaling pathway involved in regulating organ size, development, homeostasis and regeneration1–4. YAP1 is a transcriptional coactivator and the primary effector of Hippo signaling. Upstream activation of the Hippo pathway leads to nuclear translocation of YAP1, which then evokes changes in gene expression and cell cycle entry5. A prior study has demonstrated nuclear translocation of YAP1 in the supporting cells of the developing utricle6, but the possible role of YAP1 in hair cell regeneration is unclear. The present study characterizes the cellular localization of YAP1 in the utricles of mice and chicks, both under normal conditions and after hair cell injury. During neonatal development of the mouse utricle, YAP1 expression was observed in the cytoplasm of supporting cells, and was also transiently expressed in the cytoplasm of hair cells. We also observed temporary nuclear translocation of YAP1 in supporting cells of the mouse utricle at short time periods after placement in organotypic culture. However, little or no nuclear translocation of YAP1 was observed after injury to the utricles of neonatal or mature mice. In contrast, a significant degree of YAP1 nuclear translocation was observed in the chicken utricle after streptomycin-induced hair cell damagein vitroandin vivo. Together, these data suggest that differences in YAP1 signaling may be partly responsible for the distinct regenerative abilities of the avian vs. mammalian inner ear.
A Phylogenetic Approach to Inferring the Order in Which Mutations Arise during Cancer Progression
Authors: Gao Yuan , Gaither Jeff , Chifman Julia , Kubatko Laura 
Published: May 2020

SummaryAlthough the role of evolutionary process in cancer progression is widely accepted, increasing attention is being given to the evolutionary mechanisms that can lead to differences in clinical outcome. Recent studies suggest that the temporal order in which somatic mutations accumulate during cancer progression is important. Single-cell sequencing provides a unique opportunity to examine the mutation order during cancer progression. However, the errors associated with single-cell sequencing complicate this task. We propose a new method for inferring the order in which somatic mutations arise within a tumor using noisy single-cell sequencing data that incorporates the errors that arise from the data collection process. Using simulation, we show that our method outperforms existing methods for identifying mutation order in most cases, especially when the number of cells is large. Our method also provides a means to quantify the uncertainty in the inferred mutation order along a fixed phylogeny. We apply our method to empirical data from colorectal and prostate cancer patients.
Taxonomic Reassignment ofPseudohaptolina Birgericomb. nov. (Haptophyta)
Authors: Gérikas Ribeiro Catherine , dos Santos Adriana Lopes , Probert Ian , Vaulot Daniel , Edvardsen Bente 
Published: May 2020

AbstractThe haptophyte genusPseudohaptolina(formerlyChrysochromulinaclade B1-3) currently harbors two species:Pseudohaptolina arcticaandPseudohap-tolina sorokinii. In addition,Chrysochromulina birgeriis expected to belong to this genus due to its morphological similarity toP. sorokinii, but has not yet been genetically characterized. A strain belonging toPseudohaptolinawas brought into culture from Arctic waters, characterized by 18S and 28S rRNA gene sequencing as well as optical and transmission electron microscopy, and deposited in the Roscoff Culture Collection with the code RCC5270. Molecular and morphological data from RCC5270 were compared with those from previously describedPseudohaptolinaandPseudohaptolina-like species. Strain RCC5270 showed strong phylogenetic affinity toP. sorokinii, but TEM observations showed that RCC5270 possesses three types of organic body scale, rather than two as originally described inP. sorokinii. We found that the occurrence of three scale types is likely to have been overlooked in the original descriptions of bothP. sorokiniiandC. birgeri. We also found that environmental metabarcodes identical to the sequence of RCC5270 were abundant in the location from whichC. birgeriwas initially described (Gulf of Finland). We conclude thatP. sorokiniiandC. birgeriare conspecific andP. sorokiniiis therefore synonymous withC. birgeri. Based on its phylogenetic placement and nomenclatural priority we propose the new combinationPseudohaptolina birgeriand emend the description of this species.
A mouse-adapted SARS-CoV-2 model for the evaluation of COVID-19 medical countermeasures
Authors: Dinnon Kenneth H. , Leist Sarah R. , Schäfer Alexandra , Edwards Caitlin E. , Martinez David R. , Montgomery Stephanie A. , West Ande , Yount Boyd L. , Hou Yixuan J. , Adams Lily E. , Gully Kendra L. , Brown Ariane J. , Huang Emily , Bryant Matthew D. , Choong Ingrid C. , Glenn Jeffrey S. , Gralinski Lisa E. , Sheahan Timothy P. , Baric Ralph S. 
Published: May 2020

AbstractCoronaviruses are prone to emergence into new host species most recently evidenced by SARS-CoV-2, the causative agent of the COVID-19 pandemic. Small animal models that recapitulate SARS-CoV-2 disease are desperately needed to rapidly evaluate medical countermeasures (MCMs). SARS-CoV-2 cannot infect wildtype laboratory mice due to inefficient interactions between the viral spike (S) protein and the murine ortholog of the human receptor, ACE2. We used reverse genetics to remodel the S and mACE2 binding interface resulting in a recombinant virus (SARS-CoV-2 MA) that could utilize mACE2 for entry. SARS-CoV-2 MA replicated in both the upper and lower airways of both young adult and aged BALB/c mice. Importantly, disease was more severe in aged mice, and showed more clinically relevant phenotypes than those seen in hACE2 transgenic mice. We then demonstrated the utility of this model through vaccine challenge studies in immune competent mice with native expression of mACE2. Lastly, we show that clinical candidate interferon (IFN) lambda-1a can potently inhibit SARS-CoV-2 replication in primary human airway epithelial cellsin vitro, and both prophylactic and therapeutic administration diminished replication in mice. Our mouse-adapted SARS-CoV-2 model demonstrates age-related disease pathogenesis and supports the clinical use of IFN lambda-1a treatment in human COVID-19 infections.
Virome composition in marine fish revealed by meta-transcriptomics
Authors: Geoghegan Jemma L. , Di Giallonardo Francesca , Wille Michelle , Ortiz-Baez Ayda Susana , Costa Vincenzo A. , Ghaly Timothy , Mifsud Jonathon C. O. , Turnbull Olivia M. H. , Bellwood David R. , Williamson Jane E. , Holmes Edward C. 
Published: May 2020

AbstractRevealing the determinants of virome composition is central to placing disease emergence in a broader evolutionary context. Fish are the most species-rich group of vertebrates and so provide an ideal model system to study the factors that shape virome compositions and their evolution. We characterised the viromes of 19 wild-caught species of marine fish using total RNA sequencing (meta-transcriptomics) combined with analyses of sequence and protein structural homology to identify divergent viruses that often evade characterisation. From this, we identified 25 new vertebrate-associated viruses and a further 22 viruses likely associated with fish diet or their microbiomes. The vertebrate-associated viruses identified here included the first fish virus in theMatonaviridae(single-strand, negative-sense RNA virus). Other viruses fell within theAstroviridae, Picornaviridae, Arenaviridae, Reoviridae, Hepadnaviridae, Paramyxoviridae, Rhabdoviridae, Hantaviridae, FiloviridaeandFlaviviridaeand were sometimes phylogenetically distinct from known fish viruses. We also show how key metrics of virome composition – viral richness, abundance and diversity – can be analysed along with host ecological and biological factors as a means to understand virus ecology. Accordingly, these data suggest that that the vertebrate-associated viromes of the fish sampled here are predominantly shaped by the phylogenetic history (i.e. taxonomic order) of their hosts, along with several biological factors including water temperature, habitat depth, community diversity and swimming behaviour. No such correlations were found for viruses associated with porifera, molluscs, arthropods, fungi and algae, that are unlikely to replicate in fish hosts. Overall, these data indicate that fish harbour particularly large and complex viromes and the vast majority of fish viromes are undescribed.
CheckV: assessing the quality of metagenome-assembled viral genomes
Authors: Nayfach Stephen , Camargo Antonio Pedro , Eloe-Fadrosh Emiley , Roux Simon , Kyrpides Nikos 
Published: May 2020

AbstractOver the last several years, metagenomics has enabled the assembly of millions of new viral sequences that have vastly expanded our knowledge of Earth’s viral diversity. However, these sequences range from small fragments to complete genomes and no tools currently exist for estimating their quality. To address this problem, we developed CheckV, which is an automated pipeline for estimating the completeness of viral genomes as well as the identification and removal of non-viral regions found on integrated proviruses. After validating the approach on mock datasets, CheckV was applied to large and diverse viral genome collections, including IMG/VR and the Global Ocean Virome, revealing that the majority of viral sequences were small fragments, with just 3.6% classified as high-quality (i.e. > 90% completeness) or complete genomes. Additionally, we found that removal of host contamination significantly improved identification of auxiliary metabolic genes and interpretation of viral-encoded functions. We expect CheckV will be broadly useful for all researchers studying and reporting viral genomes assembled from metagenomes. CheckV is freely available at:http://bitbucket.org/berkeleylab/CheckV.
Systematic review and meta-analysis of the prevalence of Strep Aemmclusters in Africa to inform vaccine development
Authors: Salie Taariq , Engel Kelin , Moloi Annesinah , Muhamed Babu , Dale James B , Engel Mark E 
Published: May 2020

AbstractBackgroundAnemm-cluster based system was proposed as a standard typing scheme to facilitate and enhance future studies of Group A Streptococcus (Strep A) epidemiological surveillance, M protein function and vaccine development strategies. We provide an evidence-based distribution of Strep Aemmclusters in Africa and assess the potential coverage of the new 30-valent vaccine in terms of an emm cluster-based approach.MethodTwo reviewers independently assessed studies retrieved from a comprehensive search and extracted relevant data. Meta-analyses were performed (random effects model) to aggregateemmcluster prevalence estimates.ResultsEight studies (n=1,595 isolates) revealed the predominantemmclusters as E6 (18%, 95% confidence interval (CI), 12.6; 24.0%), followed by E3 (14%, 95%CI, 11.2; 17.4%) and E4 (13%, 95%CI, 9.5; 16.0%). There is negligible variation inemmclusters as regards regions, age and socio-economic status across the continent. Considering anemmcluster-based vaccine strategy, which assumes cross-protection within clusters, the 30-valent vaccine currently in clinical development, would provide hypothetical coverage to 80.3% of isolates in Africa.ConclusionThis systematic review indicates the most predominant Strep Aemmcluster in Africa is E6 followed by E3, E4 and D4. The current 30-valent vaccine would provide considerable coverage across the diversity ofemmcluster types in Africa. Future efforts could be directed toward estimating the overall potential coverage of the new 30-valent vaccine based on cross-opsonization studies with representative panels of Strep A isolates from populations at highest risk for Strep A diseases.ImportanceLow vaccine coverage is of grave public health concern, particularly in developing countries where epidemiological data are often absent. To inform vaccine development for group A streptococcus (Strep A), we report on the epidemiology of the M Protein emm clusters from Strep A infections in Africa, where Strep A-related illnesses and their sequalae including rheumatic fever and rheumatic heart disease, are of a high burden. This first report of emm clusters across the continent indicate a high probably of coverage by the M Protein-based vaccine currently undergoing testing, were an emm-cluster based approach to be used.
ATAC-seq identifies chromatin landscapes linked to the regulation of oxidative stress in the human fungal pathogenCandida albicans
Authors: Jenull Sabrina , Tscherner Michael , Mair Theresia , Kuchler Karl 
Published: May 2020

AbstractHuman fungal pathogens often encounter fungicidal stress conditions upon host invasion, but they can swiftly adapt by transcriptional reprogramming that enables pathogen survival. Fungal immune evasion is tightly connected to chromatin regulation. Hence, fungal chromatin modifiers pose alternative treatment options to combat fungal infections. Here, we present an ATAC-seq protocol adapted for the opportunistic pathogenCandida albicansto gain further insight into the interplay of chromatin accessibility and gene expression mounted during fungal adaptation to oxidative stress. The ATAC-seq workflow facilitates the robust detection of genomic regions with accessible chromatin, but also allows for the precise modeling of nucleosome positions inC. albcians. Importantly, the data reveal genes with altered chromatin accessibility in upstream regulatory regions, which correlate with transcriptional regulation during the oxidative stress response. Interestingly, many genes show increased chromatin accessibility yet no change in gene expression upon stress exposure. Such chromatin signatures could predict yet unknown regulatory factors under highly dynamic transcriptional control. In addition,de novomotif analysis in genomic regions with increased chromatin accessibility upon hydrogen peroxide treatment shows significant enrichment for Cap1 binding sites, a major factor of oxidative stress responses inC. albicans. Taken together, the ATAC-seq workflow enables the identification of chromatin signatures and uncovers the dynamics of regulatory mechanisms mediating environmental adaptation ofC. albicansto host immune surveillance.ImportanceThe opportunistic fungal pathogenCandida albicanscolonizes and infects various tissues and organs of the human host. This is due to its rapid environmental adaptation facilitated by changes in gene expression coupled to chromatin alterations. Recent advances in chromatin profiling approaches, such as the development of ATAC-seq, shed light on the dynamic interplay of chromatin accessibility and transcriptional control. The here presented expansion of the ATAC-seq method toC. albicansdemonstrates the robustness of ATAC-seq to detect dynamic modulations of chromatin accessibility in response to oxidative stress. This work serves as a basis to further exploit this application to characterize regulatory mechanisms that drive fungal environmental adaptation, such as during host invasion, and thus, will open novel antifungal treatment strategies targeting fungal chromatin regulation.
A temperature-dependent translational switch controls biofilm development inVibrio cholerae
Authors: Peso Santos Teresa del , Blake Jonathon , Sit Brandon , Warr Alyson R. , Benes Vladimir , Waldor Matthew K. , Cava Felipe 
Published: May 2020

AbstractThe gastrointestinal pathogenVibrio choleraefrequently forms biofilms during its life cycle. Biofilm formation is vital for protection against environmental stresses and is thought to facilitate intestinal colonization. Adaptation to temperature is crucial forV. choleraesurvival, as the pathogen is exposed to seasonal temperature variations in the aquatic environment, and temperature fluctuations during host-environment transitions. Here, we show thatV. choleraestrains naturally lacking the master biofilm transcriptional regulator HapR are unable to develop colony rugosity at low temperatures. We find that BipA, a ribosome-associated GTPase, accounts for this temperature-dependent control of biofilm formation by repressing translation of the primary biofilm transcriptional activators VpsR and VpsT at low temperatures.In vitrostudies demonstrate that low temperatures influence BipA structural conformation and decrease its sensitivity to proteolysis. Proteomic analyses reveal that BipA exerts temperature-dependent control over >200 proteins inV. choleraeinvolved in a multitude of cell processes, including biofilm assembly. Our study reveals a remarkable new facet of the complexV. choleraebiofilm regulatory cascade and suggests that combined transcriptional-translational control could be a common mechanism by which bacteria adapt to environmental flux.