bluuebunny/crossref_metadata_2025 huggingface dataset:
Do maternal intrauterine environmental influences that lower offspring birthweight causally increase offspring cardiometabolic risk factors in later life? A Mendelian randomization study of 45,849 genotyped parent offspring pairs in the HUNT study
Authors: Moen Gunn-Helen , Brumpton Ben , Willer Cristen , Åsvold Bjørn Olav , Birkeland Kåre , Neale Michael C , Freathy Rachel M , Smith George Davey , Lawlor Deborah A , Kirkpatrick Robert M , Warrington Nicole M , Evans David M
Published: May 2020

Introduction

There is a robust and well-documented observational relationship between lower birthweight and higher risk of cardiometabolic disease in later life. The Developmental Origins of Health and Disease (DOHaD) hypothesis posits that adverse environmental factors in utero or in the early years of life result in increased future risk of cardiometabolic disease. Our aim was to investigate whether there was evidence for causal effects of the intrauterine environment, as proxied by maternal single nucleotide polymorphisms (SNPs) that influence offspring birthweight independent of offspring genotype, on offspring cardiometabolic risk factors such as blood pressure, non-fasting glucose, body mass index (BMI), and lipid levels.

Methods

We investigated whether a genetic risk score of maternal SNPs associated with offspring birthweight was also associated with offspring cardiometabolic risk factors, after controlling for offspring genotypes at the same loci, in up to 26,057 mother-offspring pairs from the Nord-Trøndelag Health (HUNT) Study. We also conducted similar analyses in 19,792 father-offspring pairs from the same study to investigate whether there was evidence that any such causal effects operated through the postnatal, rather than the intrauterine environment. To take account of the considerable cryptic relatedness in HUNT, we implemented a computationally efficient genetic linear mixed model using the OpenMx software package to perform our analyses.

Results

We found little evidence for a maternal genetic effect of birthweight associated variants on offspring cardiometabolic risk factors after adjusting for offspring genotypes at the same loci. Likewise, we found little evidence for paternal genetic effects on offspring cardiometabolic risk factors performing similar analyses in father-offspring pairs. In contrast, offspring genetic risk scores of birthweight associated variants were strongly related to many cardiometabolic risk factors, even after conditioning on maternal genotypes at the same loci.

Conclusion

Our results suggest that the maternal intrauterine environment, as proxied by maternal SNPs that influence offspring birthweight, is unlikely to be a major determinant of adverse cardiometabolic outcomes in population based samples of individuals. In contrast, genetic pleiotropy appears to explain some of the observational relationship between offspring birthweight and future cardiometabolic risk.
Genetic and environmental determinants of variation in the plasma lipidome of older Australian twins
Authors: Wong Matthew W.K. , Thalamuthu Anbupalam , Braidy Nady , Mather Karen A. , Liu Yue , Ciobanu Liliana , Baune Bernhardt T. , Armstrong Nicola J. , Kwok John , Schofield Peter R. , Wright Margaret J. , Ames David , Pickford Russell , Lee Teresa , Poljak Anne , Sachdev Perminder S.
Published: May 2020

The critical role of blood lipids in a broad range of health and disease states is well recognised, while an understanding of the complex genetic regulation of lipid homeostasis is emerging. Traditional blood lipids (LDL-C, HDL-C and triglycerides) are known to be substantially regulated by genetic variation. Less well explored is the interplay of genetics and environment within the broader blood lipidome. Here we use the twin model to examine heritability of the plasma lipidome among healthy older aged twins and explore gene expression and epigenetic (DNA methylation) associations of these lipids. Heritability of 209 plasma lipids quantified by liquid chromatography coupled mass spectrometry (LC-MS) was assessed in 75 monozygotic and 55 dizygotic twin pairs enrolled in the Older Australian Twins Study (OATS), aged 69-93 years. Only 27/209 lipids (13.3%) were significantly heritable under the classical ACE twin model (h2= 0.28-0.59). Ceramides (Cer) and triglycerides (TG) were most heritable, while sphingomyelins (SM) and most phospholipids, especially lysophospholipids, were not significantly heritable. Lipid levels correlated with 3731 transcripts. Relative to non-significantly heritable TGs, heritable TGs had a greater number of associations with gene transcripts, which were not directly associated with lipid metabolism, but with immune function, signalling and transcriptional regulation. Genome-wide average DNA methylation (GWAM) levels accounted for a proportion of variability in some non-heritable lipids, especially lysophosphatidylcholine (LPC). We found a complex interplay of genetic and environmental influences on the ageing plasma lipidome, with most of the variation controlled by unique environmental influences.
Alternative Lengthening of Telomeres is not synonymous with mutations in ATRX/DAXX
Authors: de Nonneville Alexandre , Reddel Roger R.
Published: May 2020

The PCAWG Consortium has recently released an unprecedented set of tumor whole genome sequence (WGS) data from 2,658 cancer patients across 38 different primary tumor sites1. WGS is able to document the quantity and distribution of telomeric repeats2. In one of the papers analyzing the PCAWG dataset, Sieverlinget al.3confirmed previous data4indicating that tumors with truncating ATRX or DAXX alterations, referred to as ATRX/DAXXtrunc, have an aberrant telomere variant repeat (TVR) distribution. By regarding these mutations,vs.TERT modifications (TERTmod; i.e. promoter mutations +/− amplifications +/− structural variations), as indicators of Alternative Lengthening of Telomeres (ALT)vs.telomerase, they built a random forest classifier for ALT-probability, and then associated genomic characteristics with the putative Telomere Maintenance Mechanism (TMM)3. However, we show here that equating ATRX/DAXXtruncand TERTmodwith ALT and telomerase, respectively, results in TMM predictions which correlate poorly with TMM assay data. ATRX/DAXXtruncmutations are heterogeneously distributed in ALT-positive (ALT+) tumors of different types, as are TERTmodin telomerase-positive tumors4. Although these mutations are strongly associated with TMM, most tumors do not harbor them, making them an inadequate basis for building a classifier in a large-scale pan-cancer study4–7. Here, we provide a new analysis of the PCAWG data, based on C-circle assay (CCA)8that is available for a subset of these tumors4,9,10. We show that the Sieverlinget al.score overestimates the proportion of ALT associated with ATRX/DAXXtruncand misclassifies ALT tumors when these mutations are absent. We also show some TVR correlate with ATRX/DAXXtruncmutations, regardless of TMM. Finally, we propose a new classifier to identify ALT tumors in the PCAWG cohort.
“A Proteogenomic workflow reveals distinct molecular phenotypes related to breast cancer appearance”
Authors: De Marchi Tommaso , Pyl Paul Theodor , Sjöstrom Martin , Klasson Stina , Sartor Hanna , Malmström Johan , Malmström Lars , Niméus Emma
Published: May 2020

Proteogenomics approaches have enabled the generation of extensive information levels when compared to single omics technology studies, although burdened by massive experimental efforts. Here, we developed four improvements of a data independent acquisition mass spectrometry proteogenomics workflow to reveal distinct molecular phenotypes related to breast cancer appearance. We confirm mutational processes detectable at the protein level and highlight quantitation and pathway complementarity between RNA and protein data. Our analyses also validated previously established enrichments of estrogen receptor-dependent molecular features relating to transcription factor expression, and provided evidence for molecular differences related to the presence of mammographic appearances in spiculated tumors. In addition, several transcript-protein pairs displayed radically different abundance correlations depending on the overall clinical and pathological properties of the tumor. These results demonstrate that there are differentially regulated protein networks in clinically relevant sample groups, and that these protein networks influence both cancer biology as well as the abundance of potential biomarkers and drug targets.
A 6.5kb intergenic structural variation enhances P450-mediated resistance to pyrethroids in malaria vectors lowering bed net efficacy
Authors: Mugenzi Leon M.J. , Menze Benjamin D. , Tchouakui Magellan , Wondji Murielle J. , Irving Helen , Tchoupo Micareme , Hearn Jack , Weedall Gareth D. , Riveron Jacob M. , Cho-Ngwa Fidelis , Wondji Charles S.
Published: May 2020

Elucidating the complex evolutionary armory that mosquitoes deploy against insecticides is crucial to maintain the effectiveness of insecticide-based interventions. Here, we deciphered the role of a 6.5kb structural variation (SV) in driving cytochrome P450-mediated pyrethroid resistance in the malaria vector,Anopheles funestus. Whole genome pooled sequencing detected an intergenic 6.5kb SV between duplicated CYP6P9a/b P450s in pyrethroid resistant mosquitoes through a translocation event. Promoter analysis revealed a 17.5-fold higher activity (P<0.0001) for the SV-carrying fragment than the SV-free one. qRT-PCR expression profiling ofCYP6P9a/bfor each SV genotype supported its role as an enhancer since SV+/SV+ homozygote mosquitoes had significantly greater expression for both genes than heterozygotes SV+/SV- (1.7-2-fold) and homozygotes SV-/SV- (4-5-fold). Designing a PCR assay revealed a strong association between this SV and pyrethroid resistance (SV+/SV+ vs SV-/SV-; OR=2079.4,P=<0.001). The 6.5kb SV is present at high frequency in southern Africa (80-100%) but absent in East/Central/West Africa. Experimental hut trials revealed that homozygote SV mosquitoes had significantly greater chance to survive exposure to pyrethroid-treated Nets (OR 27.7; P < 0.0001) and to blood feed than susceptible. Furthermore, triple homozygote resistant (SV+/CYP6P9a_R/CYP6P9b_R) exhibit a higher resistance level leading to a far superior ability to survive exposure to nets than triple susceptible mosquitoes, revealing a strong additive effect. This study highlights the important role of structural variations in the development of insecticide resistance in malaria vectors and their detrimental impact on the effectiveness of pyrethroid-based nets.
Delay of gratification in non-human animals: A review of inter-specific variation in performance
Authors: Susini Irene , Safryghin Alexandra , Hillemann Friederike , Wascher Claudia A.F.
Published: May 2020

The ability to regulate and withhold an immediate behaviour in pursuit of a more preferred or valuable, albeit delayed, outcome is regarded as an important cognitive ability enabling adaptive decision-making in both social and asocial contexts. Abilities to cope with a delay in gratification have been investigated in a range of species using a variety of experimental paradigms. The present study attempts a first systematic evaluation of available experimental data from non-human animals, which is an essential basis for quantifying biological and non-biological factors (e.g.socio-ecologyversusexperimental design) affecting performance in delay of gratification tasks. Data were sourced from 52 separate studies, and a comprehensive overview of the available literature on delay of gratification in non-human animals is presented. We present data from 21 species, spanning across eight taxonomic order, with 1–9 species tested per taxonomic group. We highlight variation in experimental paradigms used to study delay of gratification abilities in non-human animals, both with regard to reward type or experimental setup, and discuss the implications for comparative analyses. We conclude that, at present, cross-species comparisons of delay of gratification abilities are hindered by a lack of consistency in experimental designs and low number of species tested across taxonomic orders. We hope to stimulate research on a more diverse set of species, and that future studies consider potential social and ecological factors that cause intra-specific variation in test performances, that is repeatedly seen across species.
Anin silicoapproach to identification, categorization and prediction of nucleic acid binding proteins
Authors: Xu Lei , Jiang Shanshan , Zou Quan
Published: May 2020

The interaction between proteins and nucleic acid plays an important role in many processes, such as transcription, translation and DNA repair. The mechanisms of related biological events can be understood by exploring the function of proteins in these interactions. The number of known protein sequences has increased rapidly in recent years, but the databases for describing the structure and function of protein have unfortunately grown quite slowly. Thus, improving such databases is meaningful for predicting protein-nucleic acid interactions. Furthermore, the mechanism of related biological events, such as viral infection or designing novel drug targets, can be further understood by understanding the function of proteins in these interactions. The information for each sequence, including its function and interaction sites, were collected and identified, and a database called PNIDB was built. The proteins in PNIDB were grouped into 27 classes, such as transcription, immune system, and structural protein, etc. The function of each protein was then predicted using a machine learning method. Using our method, the predictor was trained on labeled sequences, and then the function of a protein was predicted based on the trained classifier. The prediction accuracy achieved a score of 77.43% by 10-fold cross validation.

Availability and Implementation

PNIDB is now fully working and can be freely accessed at:http://server.malab.cn/PNIDB/index.html. All the data are publicly available for non-commercial use, distribution, and reproduction in any medium.

Contact

zouquan@nclab.net
Microbe-dependent heterosis in maize
Authors: Wagner Maggie R. , Tang Clara , Salvato Fernanda , Clouse Kayla M. , Bartlett Alexandria , Sermons Shannon , Hoffmann Mark , Balint-Kurti Peter J. , Kleiner Manuel
Published: May 2020

Hybrids account for nearly all commercially planted varieties of maize and many other crop plants, because crosses between inbred lines of these species produce F1 offspring that greatly outperform their parents. The mechanisms underlying this phenomenon, calledheterosisor hybrid vigor, are not well understood despite over a century of intensive research (1). The leading hypotheses—which focus on quantitative genetic mechanisms (dominance, overdominance, and epistasis) and molecular mechanisms (gene dosage and transcriptional regulation)—have been able to explain some but not all of the observed patterns of heterosis (2, 3). However, possible ecological drivers of heterosis have largely been ignored. Here we show that heterosis of root biomass and germination in maize is strongly dependent on the belowground microbial environment. We found that, in some cases, inbred lines perform as well by these criteria as their F1 offspring under sterile conditions, but that heterosis can be restored by inoculation with a simple community of seven bacterial strains. We observed the same pattern for seedlings inoculated with autoclavedvs.live soil slurries in a growth chamber, and for plants grown in fumigatedvs.untreated soil in the field. Together, our results demonstrate a novel, ecological mechanism for heterosis whereby soil microbes generally impair the germination and early growth of inbred but not hybrid maize.
Evolution of symbiont transmission in conditional mutualisms in spatially and temporally variable environments
Authors: Brown Alexandra , Akçay Erol
Published: May 2020

Symbiotic relationships affect the fitness and organismal function of virtually all organisms. In many cases, the fitness effects of symbiosis may be beneficial or harmful depending on the environment. The hosts of such symbionts are favored to acquire them only when the symbiont is beneficial. However, it is not clear whether such selection favors vertical or horizontal transmission, both, or neither. To address this question, we model the evolution of transmission mode in a conditional mutualism experiencing spatial and temporal environmental variation. We find that when symbionts affect host lifespan, but not fecundity, horizontal transmission can contain them to beneficial environments. Vertical transmission can produce symbiont containment when the environmental state is synchronized across locations. We also find an emergent trade-off between horizontal and vertical transmission, suggesting that physiological constraints are not required for the evolution of limits on the total amount of transmission.
Hypotheses and models linking epigenetic transgenerational effects to population dynamics: Exploring oscillations and applications to wildlife cycles
Authors: Juckett David
Published: May 2020

Epigenetic transgenerational mechanisms underpin the imprinting of gamete origin during reproduction in mammals but are also hypothesized to transmit environmental exposures from parents to progeny in many life forms, which could have important consequences in population dynamics. Transgenerational hypotheses embody epigenetic alterations occurring in gametes, embryonic somatic cells, and embryonic primordial germ cells because most of the epigenome is erased and reconstituted during development. Four scenarios are described in this paper encompassing somatic and germline effects where each of these is either non-propagating or propagating in time. The non-propagating effects could result from environmental impulses such as toxicants, weather, epidemics, forest fires, etc. The propagating effects could result from continuous signals such as climate variations, food web abundances, population densities, predator numbers, etc. Focusing on the propagating mode, a population growth model is constructed incorporating the intrinsic delays associated with somatic or germline effects. Each exhibit oscillatory behavior over a wide range of the parameter space due to the inherent negative feedback of such delays. The somatic (maternal) model oscillates with a period of ∼6 generations while the germline (grandmaternal) model oscillates with a period of ∼10 generations. These models can be entrained by oscillatory external signals providing that the signals contain harmonic components near the intrinsic oscillations of the models. The 10-generation oscillation of the germline-effects model is similar to many wildlife cycles in mammals, bird, and insects. The possibility that such a transgenerational mechanism is a component of these wildlife cycles is discussed.
HybridMine: pipeline for allele inheritance and gene copy number prediction in industrial yeast hybrids
Authors: Timouma Soukaina , Schwartz Jean-Marc , Delneri Daniela
Published: May 2020

Saccharomyces pastorianusis an allopolyploid sterile yeast hybrid used in brewing to produce lager-style beers. The development of new yeast strains with valuable industrial traits such as improved maltose utilization or balanced flavour profiles are now a major ambition and challenge in craft brewing and distilling industries. Genome-scale computational approaches are opening opportunities to model and predict favourable combination of traits for strain development. However, mining the genome of these complex hybrids is not currently an easy task, due to the high level of redundancy and presence of homologous. Moreover, no genome annotation for these industrial strains have been published. Here, we developed HybridMine, a new user-friendly, open-source tool for functional annotation of hybrid aneuploid genomes of any species by predicting parental alleles including paralogs. As proof of principle, we carried out a comprehensive structural and functional annotation of complex yeast hybrids to enable system biology prediction studies. HybridMine is developed in Python, Perl and Bash programming languages and is available athttps://github.com/Sookie-S/HybridMine.
Benchmarking available bacterial promoter prediction tools: potentialities and limitations
Authors: Anzolini Cassiano Murilo Henrique , Silva-Rocha Rafael
Published: May 2020

Background

The promoter region is a key element required for the production of RNA in bacteria. While new high-throughput technology allows massive mapping of promoter elements, we still mainly relay on bioinformatic tools to predict such elements in bacterial genomes. Additionally, despite many different prediction tools have become popular to identify bacterial promoters, there is no systematic comparison of such tools.

Results

Here, we performed a systematic comparison between several widely used promoter prediction tools (BPROM, bTSSfinder, BacPP, CNNProm, IBBP, Virtual Footprint, IPro70-FMWin, 70ProPred, iPromoter-2L and MULTiPly) using well-defined sequence data sets and standardized metrics to determine how well those tools performed related to each other. For this, we used datasets of experimentally validated promoters fromEscherichia coliand a control dataset composed by randomly generated sequences with similar nucleotide distributions. We compared the performance of the tools using metrics such as specificity, sensibility, accuracy and Matthews Correlation Coefficient (MCC). We show that the widely used BPROM presented the worse performance among compared tools, while four tools (CNNProm, IPro70-FMWin, 70ProPreda and iPromoter-2L) offered high predictive power. From these, iPro70-FMWin exhibited the best results for most of the metrics used.

Conclusions

Therefore, we exploit here some potentials and limitations of available tools and hope future works can be built upon our effort to systematically characterize such quite useful class of bioinformatics tools.
Immunodietica: interrogating the role of diet in autoimmune disease
Authors: Gershteyn Iosif M. , Burov Andrey A. , Miao Brenda Y. , Morais Vasco H. , Ferreira Leonardo M. R.
Published: May 2020

Diet is an environmental factor in autoimmune disorders, where the immune system erroneously destroys one’s own tissues. Yet, interactions between diet and autoimmunity remain largely unexplored, particularly the impact of immunogenetics, one’s human leukocyte antigen (HLA) allele make-up, in this interplay. Here, we interrogated animals and plants for the presence of epitopes implicated in human autoimmune diseases. We mapped autoimmune epitope distribution across organisms and determined their tissue expression pattern. Interestingly, diet-derived epitopes implicated in a disease were more likely to bind to HLA alleles associated with that disease than to protective alleles, with visible differences between organisms with similar autoimmune epitope content. We then analyzed an individual’s HLA haplotype, generating a personalized heatmap of potential dietary autoimmune triggers. Our work uncovered differences in autoimmunogenic potential across food sources and revealed differential binding of diet-derived epitopes to autoimmune disease-associated HLA alleles, shedding light on the impact of diet on autoimmunity.
Sampling bias exaggerates a textbook example of a trophic cascade
Authors: Brice Elaine M. , Larsen Eric J. , MacNulty Daniel R.
Published: May 2020

Understanding how ecosystems respond to the loss and recovery of large predators is a major challenge because these free-living systems are difficult to sample properly. We show how an accepted practice of nonrandom sampling has confounded this understanding in a textbook system (Yellowstone National Park) where carnivore [Canis lupus(wolf)] recovery is often associated with a trophic cascade involving changes in herbivore [Cervus canadensis(elk)] behavior and density that promote plant regeneration. Long-term data indicate that a customary practice of sampling only the tallest young plants overestimated regeneration of overstory aspen (Populus tremuloides) by a factor of 3-8 compared to random sampling. Sampling only the tallest young plants favored plants taller than the preferred browsing height of elk and overlooked non-regenerating aspen stands. Our results demonstrate how seemingly minor departures from principled sampling can generate substantial misunderstandings about the strength of trophic cascades in response to large predator recovery.
The fully resolved genome ofBacillus thuringiensisHER1410 reveals acry-containing chromosome, two megaplasmids & an integrative plasmidial prophage
Authors: Lechuga Ana , Lood Cédric , Salas Margarita , Vera van Noort V. , Lavigne Rob , Redrejo-Rodríguez Modesto
Published: May 2020

Bacillus thuringiensisis the most used biopesticide in agriculture. Its entomopathogenic capacity stems from the possession of plasmid-borne insecticidal crystal genes (cry), traditionally used as discriminant taxonomic feature for that species. As such, crystal and plasmid identification are key to the characterization of this species. To date, about 600B. thuringiensisgenomes have been reported, but less than 5% have been resolved, while the other draft genomes are incomplete, precluding plasmid delineation. Here we present the complete genome ofBacillus thuringiensisHER1410, a strain closely related toB. thuringiensis entomocidusand a known host for a variety ofBacillusphages. The combination of short and long-reads techniques allowed fully resolving the genome and delineation of three plasmids. This enabled the accurate detection of an unusual location of a uniquecrygene,cry1Ba4,located in a genomic island near the chromosome replication origin. Two megaplasmids, pLUSID1 and pLUSID2 could be delineated: pLUSID1 (368kb), a likely conjugative plasmid involved in virulence, and pLUSID2 potentially related to the sporulation process. A smaller plasmidial prophage pLUSID3, with a dual lifestyle whose integration within the chromosome, causes the disruption of a flagellar key component. Finally, phylogenetic analysis located this strain within a clade comprising members from theB. thuringiensisserovarthuringiensisand other serovars and withB.cereus s. s.This highlights the intermingled taxonomy ofB. cereus sensu latogroup, where genomics alone does not support the present taxonomy betweenB. cereus s. s.andB. thuringiensisas species designation currently relies solely on the presence of entomocidal genes.

Importance

Bacillus cereusgroup species have been extensively studied due to their economical and clinical relevance. This importance originally set the basis forB. cereusgroup members classification which are commonly based on phenotypical criteria. Sequencing era has shed light about genomic characterization of these species, showing their chromosomal genomic similarity and highlighting the role of mobile genetic elements, especially megaplasmids, in the classification and characterization of this group. However, only the 5% of the sequencedB. thuringiensisgenomes have been fully resolved. Thus, here we addressed efficiently the studyB. thuringiensisHER1410 genomic features by the use of a combination of short and long-reads sequencing. This methodology resulted in the high-quality assembly, which led to the identification of an uncommon location of acrygene close to the chromosomal origin, as well as three fully resolved extrachromosomal elements, two megaplasmids and an integrative plasmidial prophage.
N-linked glycan sites on the influenza NA head domain are required for efficient IAV incorporation and replication
Authors: Östbye Henrik , Gao Jin , Martinez Mira Rakic , Wang Hao , de Gier Jan-Willem , Daniels Robert
Published: May 2020

N-linked glycans commonly contribute to secretory protein folding, sorting and signaling. For enveloped viruses such as the influenza A virus (IAV), the addition of largeN-linked glycans can also prevent access to epitopes on the surface antigens hemagglutinin (HA or H) and neuraminidase (NA or N). Sequence analysis showed that in the NA head domain of H1N1 IAVs three N-linked glycosylation sites are conserved and that a fourth site is conserved in H3N2 IAVs. Variable sites are almost exclusive to H1N1 IAVs of human origin, where the number of head glycosylation sites first increased and then decreased over time. In contrast, variable sites exist in H3N2 IAVs of human and swine origin, where the number of head glycosylation sites has mainly increased over time. Analysis of IAVs carrying N1 and N2 mutants demonstrated that theN-linked glycosylation sites on the NA head domain are required for efficient virion incorporation and replication in cells or eggs. It also revealed that N1 stability is more affected by the head domain glycans, suggesting N2 is more amenable to glycan additions. Together, these results indicate that in addition to antigenicity, N-linked glycosylation sites can alter NA enzymatic stability and the NA amount in virions.
Covid-19 prevalence estimation by random sampling in the wider population - Optimal sample pooling under varying assumptions about true prevalence
Authors: Brynildsrud Ola
Published: May 2020

The number of confirmed Covid-19 cases in a population is used as a coarse measurement for the burden of disease. However, this number depends heavily on the sampling intensity and the various test criteria used in different jurisdictions. A wide range of sources indicate that a large fraction of cases go undetected. Estimates of the true prevalence of Covid-19 can be made by random sampling in the wider population. Here we use simulations to explore confidence intervals of prevalence estimates under different sampling intensities and degrees of sample pooling.
The potential impact of human visceral leishmaniasis vaccines on population incidence
Authors: le Rutte Epke A , Coffeng Luc E , Malvolti Stefano , Kaye Paul M. , de Vlas Sake J
Published: May 2020

Background

Human visceral leishmaniasis (VL) vaccines are currently under development and there is a need to understand their potential impact on population wide VL incidence.

Methodology / Principal Findings

We implement four characteristics from different human VL vaccine candidates into two published VL transmission model variants to estimate the potential impact of these vaccine characteristics on population-wide anthroponotic VL incidence on the Indian subcontinent (ISC). The vaccines that are simulated in this study 1) reduce the infectiousness of infected individuals towards sand flies, 2) reduce risk of developing symptoms after infection, 3) reduce the risk of developing post-kala-azar dermal leishmaniasis (PKDL), or 4) lead to the development of transient immunity. We also compare and combine a vaccine strategy with current interventions to identify their potential role in elimination of VL as public health problem. We show that the first two simulated vaccine characteristics can greatly reduce VL incidence. For these vaccines, an approximate 60% vaccine efficacy would lead to achieving the ISC elimination target (<1 VL case per 10,000 population per year) within 10 years’ time in a moderately endemic setting when vaccinating 100% of the population. Vaccinating VL cases to prevent the development of PKDL is a promising tool to sustain the low incidence elimination target after regular interventions are halted. Vaccines triggering the development of transient immunity protecting against infection lead to the biggest reduction in VL incidence, but booster doses are required to achieve perduring impact.

Conclusions / Significance

Even though vaccines are not yet available for implementation, their development should be pursued as their potential impact on transmission can be substantial, both in decreasing incidence at the population level as well as in sustaining the ISC elimination target when other interventions are halted.

Author summary

Vaccines for human visceral leishmaniasis (VL) are currently under development. In this study, we simulate VL transmission dynamics using mathematical models to explore the potential impact of vaccines on population-wide incidence. We show that some vaccines have high potential to reduce VL incidence, namely those that reduce the infectiousness of infected individuals to sand flies and those that reduce the chance of developing symptoms once infected. The effect of vaccines that lead to protection from infection is potentially the greatest, but depending on the duration of immunity, individuals would require booster doses to guarantee lifelong impact. Vaccines that prevent the development of post-kala-azar dermal leishmaniasis are a promising tool to sustain low VL incidence and prevent recrudescence of infection when regular interventions are halted. Our results strongly support the continued development of VL vaccines, as their potential impact on population incidence can be substantial.
Assessing the intrinsic and extrinsic drivers and targeting the observed resilience of malaria in northwestern and southern Tanzania: A protocol for a cross-sectional exploratory study
Authors: Chiduo Mercy G. , Mandara Celine I. , Rumisha Susan F. , Chaky Frank , Francis Filbert T. , Mmbando Bruno P. , Seth Misago D. , Challe Daniel P. , Ndekuka Leah , Massawe Isolide S. , Liheluka Edwin , Makunde Williams H. , Mhina Athanas D. , Baraka Vito , Segeja Method D. , Derua Yahya A. , Batengana Berndard M. , Hayuma Paul M. , Nkya Gineson , Madebe Rashid A. , Malimi Masunga C. , Mandike Renata , Mkude Sigsbert , Molteni Fabrizio , Njau Ritha , Mohamed Ally , Ishengoma Deus S.
Published: May 2020

Background

Despite high coverage and successes in malaria control strategies, some areas of Tanzania have indicated stagnantion or revesal of malaria burden. In malaria research, most studies are designed to assess drivers of malaria transmission focusing only on one dimension, single location while very few studies assess multiple components and their interactions at once. This article describes the protocol used to assess intrinsic and extrinsic drivers of persistent malaria transmission (hotsposts) in four regions from northwestern (Geita and Kigoma) and southern (Ruvuma and Mtwara) Tanzania.

Methods

This cross-sectional study was conducted between July and November 2017 in eight districts (two from each region). Based on the health facilities records, two villages were selected from each district. The study assessed five components individually and their linkages: socio-economic and malaria risk factors, parasitological, entomological, socio-anthropological and health system factors. Households (HHs) and household members were enumerated, socio-economic status and risk factors associated with malaria transmission were assessed. A total of 120 HHs were sampled from each village where malaria testing using rapid test and microscopy were done and blood spots on filter papers for genetic studies were collected. Heads of HHs were interviewed to capture information on knowledge, attitude, practice and beliefs towards malaria and its control. Assessment of adult mosquitoes in 25 HHs in each village and complimented with assessment of immature mosquitoes through larvae was conducted. The performance of the health system was assessed with respect to Information on availability, accessibility, affordability and quality of malaria prevention and case management services were collected from these health facilities.

Discussion

The proposed analysis plan and results from this study are expected to determine factors potentially responsible for persistence of malaria (hotspots) in the study areas. Rather than the traditional methodology of focusing on one metric, the approach proposed here triangulates observations from all five components, highlighting understanding of potential drivers while studying their complex interactions and map spatial heterogeneity. This study will provide an important framework and data which will guide future studies and malaria surveillance in Tanzania and other malaria endemic countries.
COVID-19 Scenarios: an interactive tool to explore the spread and associated morbidity and mortality of SARS-CoV-2
Authors: Noll Nicholas B , Aksamentov Ivan , Druelle Valentin , Badenhorst Abrie , Ronzani Bruno , Jefferies Gavin , Albert Jan , Neher Richard A
Published: May 2020

The ongoing SARS-CoV-2 pandemic has caused large outbreaks around the world and every heavily affected community has experienced a substantial strain on the health care system and a high death toll. Communities therefore have to monitor the incidence of COVID-19 carefully and attempt to project the demand for health care. To enable such projections, we have developed an interactive web application that simulates an age-structured SEIR model with separate compartments for severely and critically ill patients. The tool allows the users to modify most parameters of the model, including age specific assumptions on severity. Infection control and mitigation measures that reduce transmission can be specified, as well as age-group specific isolation.

The simulation of the model runs entirely on the client side in the browser; all parameter settings and results of the simulation can be exported for further downstream analysis. The tool is available at covid19-scenarios.org and the source code atgithub.com/neherlab/covid19_scenarios.
Evolution of COVID-19 pandemic: Power-law growth and saturation
Authors: Chatterjee Soumyadeep , Asad Ali , Shayak B. , Bhattacharya Shashwat , Alam Shadab , Verma Mahendra K.
Published: May 2020

In this paper, we analyze the real-time infection data of COVID-19 epidemic for 21 nations up to June 30, 2020. For most of these nations, the total number of infected individuals exhibits a succession of exponential growth and power-law growth before the flattening of the curve. In particular, we find a universal growth before they reach saturation. However, at present, India, which has I(t) ~ t2, and Russia and Brazil, which have I(t) ~ t, are yet to flatten their curves. Thus, the polynomials of the I(t) curves provide valuable information on the stage of the epidemic evolution, thus on the life cycle of COVID-19 pandemic. Besides these detailed analyses, we compare the predictions of an extended SEIR model and a delay differential equation-based model with the reported infection data and observed good agreement among them, including the behaviour. We argue that the power laws in the epidemic curves may be due to lockdowns.
Health seeking behaviors of patients with acute respiratory infections during the outbreak of novel coronavirus disease 2019 in Wuhan, China
Authors: Yang Juan , Gong Hui , Chen Xinhua , Chen Zhiyuan , Deng Xiaowei , Qian Mengcen , Hou Zhiyuan , Ajelli Marco , Viboud Cecile , Yu Hongjie
Published: May 2020

We conducted two surveys to evaluate the health-seeking behaviors of individuals with acute respiratory infections (ARI) during the COVID-19 outbreak in Wuhan, China. Among 351 participants reporting ARI (10.3%, 351/3,411), 36.5% sought medical assistance. Children were more likely to seek medical assistance than other age groups (66.1% vs. 28.0%-35.1%).
Modelling exit strategies for the UK Covid-19 lockdown with revised mortality data
Authors: Lander Anthony D. , Subramanian Thejasvi
Published: May 2020

The number of daily deaths, reported by Public Health England (PHE) during the UK Covid-19 epidemic, initially omitted out-of-hospital deaths in England. The epidemic has been mitigated by social distancing and the lockdown introduced on 17 and 23 March 2020 respectively. We recently reported a stochastic model of a mitigated epidemic which incorporated changes in social interactions and daily movements and whose simulations were consistent with the initial PHE daily mortality data. However, on 29 April, PHE revised their historic data to include out-of-hospital deaths in England. Out-of-hospital deaths occur sooner than in-hospital deaths. Here we show that if 20% of deaths, representing out-of-hospital deaths, are assigned a shorter illness period, then simulated daily mortality matches the revised PHE mortality at least until 4 May. We now predict that if the lockdown is gently relaxed in late May, whilst maintaining social distancing, there would be a modest second-wave which may be acceptable when weighed against the risks of maintaining the lockdown. Our model complements other more sophisticated work currently guiding national policy but which is not presently in the public domain.
Acceptability of app-based contact tracing for COVID-19: Cross-country survey evidence
Authors: Altmann Samuel , Milsom Luke , Zillessen Hannah , Blasone Raffaele , Gerdon Frederic , Bach Ruben , Kreuter Frauke , Nosenzo Daniele , Toussaert Séverine , Abeler Johannes
Published: May 2020

Background

The COVID-19 pandemic is the greatest public health crisis of the last 100 years. Countries have responded with various levels of lockdown to save lives and stop health systems from being overwhelmed. At the same time, lockdowns entail large socio-economic costs. One exit strategy under consideration is a mobile phone app that traces close contacts of those infected with COVID-19. Recent research has demonstrated the theoretical effectiveness of this solution in different disease settings. However, concerns have been raised about such apps because of the potential privacy implications. This could limit the acceptability of app-based contact tracing among the general population. As the effectiveness of this approach increases strongly with app take-up, it is crucial to understand public support for this intervention.

Objectives

The objective of this study is to investigate user acceptability of a contact-tracing app in five countries hit by the pandemic.

Methods

We conducted a multi-country, large-scale (N = 5995) study to measure public support for digital contact tracing of COVID-19 infections. We ran anonymous online surveys in France, Germany, Italy, the UK and the US. We measured intentions to use a contact-tracing app across different installation regimes (voluntary installation vs. automatic installation by mobile phone providers), and studied how these intentions vary across individuals and countries.

Results

We found strong support for the app under both regimes, in all countries, across all sub-groups of the population, and irrespective of regional-level COVID-19 mortality rates. We investigated the main factors that may hinder or facilitate take-up and found that concerns about cyber security and privacy, together with lack of trust in government, are the main barriers to adoption.

Conclusions

Epidemiological evidence shows that app-based contact-tracing can suppress the spread of COVID-19 if a high enough proportion of the population uses the app and that it can still reduce the number of infections if take-up is moderate. Our findings show that the willingness to install the app is very high. The available evidence suggests that app-based contact tracing may be a viable approach to control the diffusion of COVID-19.
Importance of Interaction Structure and Stochasticity for Epidemic Spreading: A COVID-19 Case Study
Authors: Großmann Gerrit , Backenköhler Michael , Wolf Verena
Published: May 2020

In the recent COVID-19 pandemic, computer simulations are used to predict the evolution of the virus propagation and to evaluate the prospective effectiveness of non-pharmaceutical interventions. As such, the corresponding mathematical models and their simulations are central tools to guide political decision-making. Typically, ODE-based models are considered, in which fractions of infected and healthy individuals change deterministically and continuously over time.

In this work, we translate an ODE-based COVID-19 spreading model from literature to a stochastic multi-agent system and use a contact network to mimic complex interaction structures. We observe a large dependency of the epidemic’s dynamics on the structure of the underlying contact graph, which is not adequately captured by existing ODE-models. For instance, existence of super-spreaders leads to a higher infection peak but a lower death toll compared to interaction structures without super-spreaders. Overall, we observe that the interaction structure has a crucial impact on the spreading dynamics, which exceeds the effects of other parameters such as the basic reproduction numberR0.

We conclude that deterministic models fitted to COVID-19 outbreak data have limited predictive power or may even lead to wrong conclusions while stochastic models taking interaction structure into account offer different and probably more realistic epidemiological insights.
Cooperative virus propagation in COVID-19 transmission
Authors: Dai Ziwei , Locasale Jason W.
Published: May 2020

The global pandemic due to the emergence of a novel coronavirus (COVID-19) is a threat to humanity. There remains an urgent need to understand its transmission characteristics and design effective interventions to mitigate its spread. In this study, we define a non-linear (known in biochemistry models as allosteric or cooperative) relationship between viral shedding, viral dose and COVID-19 infection propagation. We develop a mathematical model of the dynamics of COVID-19 to link quantitative features of viral shedding, human exposure and transmission in nine countries impacted by the ongoing COVID-19 pandemic, and state-wide transmission in the United States of America (USA). The model was then used to evaluate the efficacy of interventions against virus transmission. We found that cooperativity was important to capture country-specific transmission dynamics and leads to resistance to mitigating transmission in mild or moderate interventions. The behaviors of the model emphasize that strict interventions greatly limiting both virus shedding and human exposure are indispensable to achieving effective containment of COVID-19. Finally, in the USA we find that by the summer of 2021, a difference of about 1.5 million deaths may be observed depending on whether the interventions are to be maintained strictly or lifted in entirety.
Pervasive prophage recombination occurs during evolution of spore-formingBacilli
Authors: Dragoš Anna , B. Priyadarshini , Hasan Zahraa , Lenz-Strube Mikael , Kempen Paul J , Maróti Gergely , Kaspar Charlotte , Bose Baundauna , Burton Briana M. , Bischofs Ilka B , Kovács Ákos T.
Published: May 2020

Phages are the main source of within-species bacterial diversity and drivers of horizontal gene transfer, but we know little about the mechanisms that drive genetic diversity of these mobile genetic elements (MGEs). Recently, we showed that a sporulation selection regime promotes evolutionary changes within SPβ prophage ofBacillus subtilis, leading to direct antagonistic interactions within the population. Herein, we reveal that under a sporulation selection regime, SPβ recombines with low copy number phi3Ts phage DNA present within theB. subtilispopulation. Recombination results in a new prophage occupying a different integration site, as well as the spontaneous release of virulent phage hybrids. Analysis ofBacillussp. strains suggests that SPβ and phi3T belong to a distinct cluster of unusually large phages inserted into sporulation-related genes that are equipped with a spore-related genetic arsenal. Comparison ofBacillussp. genomes indicates that similar diversification of SPβ-like phages takes place in nature. Our work is a stepping stone toward empirical studies on phage evolution, and understanding the eco-evolutionary relationships between bacteria and their phages. By capturing the first steps of new phage evolution, we reveal striking relationship between survival strategy of bacteria and evolution of their phages.