bluuebunny/crossref_metadata_2025 huggingface dataset:
An Algorithm for Classifying Patients Most Likely to Develop Severe Coronavirus Disease 2019 Illness
Authors: Kattan Michael W. , Ji Xinge , Milinovich Alex , Adegboye Janet , Duggal Abhijit , Dweik Raed , Khouli Hassan , Gordon Steve , Young James B. , Jehi Lara
Published: December 2020

Objectives:

To develop an algorithm that predicts an individualized risk of severe coronavirus disease 2019 illness (i.e., ICU admission or death) upon testing positive for coronavirus disease 2019.

Design:

A retrospective cohort study.

Setting:

Cleveland Clinic Health System.

Patients:

Those hospitalized with coronavirus disease 2019 between March 8, 2020, and July 13, 2020.

Interventions:

A temporal coronavirus disease 2019 test positive cut point of June 1 was used to separate the development from validation cohorts. Fine and Gray competing risk regression modeling was performed.

Measurements and Main Results:

The development set contained 4,520 patients who tested positive for coronavirus disease 2019 between March 8, 2020, and May 31, 2020. The validation set contained 3,150 patients who tested positive between June 1 and July 13. Approximately 9% of patients were admitted to the ICU or died of coronavirus disease 2019 within 2 weeks of testing positive. A prediction cut point of 15% was proposed. Those who exceed the cutoff have a 21% chance of future severe coronavirus disease 2019, whereas those who do not have a 96% chance of avoiding the severe coronavirus disease 2019. In addition, application of this decision rule identifies 89% of the population at the very low risk of severe coronavirus disease 2019 (< 4%).

Conclusions:

We have developed and internally validated an algorithm to assess whether someone is at high risk of admission to the ICU or dying from coronavirus disease 2019, should he or she test positive for coronavirus disease 2019. This risk should be a factor in determining resource allocation, protection from less safe working conditions, and prioritization for vaccination.
Imaging Ultrasound Assessment of Exercise-Induced Endothelial Shear Stress of the Brachial and Carotid Arteries
Authors: Gurovich Alvaro N. , Rodriguez Lisa , Gomez Manuel , Caraveo Paulina , Ochoa Luis , Morales-Acuna Francisco
Published: December 2020

Endothelial shear stress (ESS) has a possible effect on regulation of gene expression in the protection against atherosclerosis. During exercise, ESS should increase as systolic blood pressure and heart rate (HR) increase too; however, it is hard to determine ESS changes during exercise. Imaging ultrasound assessment of the brachial and the carotid arterial blood flow during exercise might help to estimate exercise-induced ESS. We present here the methodology at the Clinical Applied Physiology Laboratory to estimate exercise-induced ESS. We normally perform 2 exercise tests in 2 different visits. First, a cardiopulmonary exercise test with serial microblood sampling to determine blood lactate (La) levels on a stationary cycle ergometer to determine maximal oxygen consumption, maximal exercising HR, and lactate threshold curve. The second exercise test includes three 5-min steady state stages determined by La levels from test 1 (La <2 mmol/L, La 2–4 mmol/L, and La >4 mmol/L). During the second test, we position an ultrasound probe holder on either the arm or neck to image the brachial or carotid arteries, respectively. We obtain images and blood flow velocities through Doppler at each exercise stage and then we analyze the images using edge detection software to determine artery diameters. With these data, we are able to estimate ESS, flow direction, and the presence of turbulent flow.
A songbird inhibits blinking behaviour in flight
Authors: Yorzinski Jessica L.
Published: December 2020

Visual attention plays a fundamental role in avian flight but attention is likely limited whenever birds blink. Because blinks are necessary to maintaining proper vision, this study tested the hypothesis that birds strategically inhibit their blinks in flight. The blinks of captive great-tailed grackles (Quiscalus mexicanus) were recorded before, during and after they flew a short distance in an open environment. The grackles spent the least amount of time blinking in flight (take-off, during flight and landing) and the most amount of time blinking at impact. Their blinking behaviour was similar before and after flight. These results suggest that grackles strategically inhibit their blinking behaviour in flight, potentially because blinks impose costs to avian flight.
Identifiability analysis for stochastic differential equation models in systems biology
Authors: Browning Alexander P. , Warne David J. , Burrage Kevin , Baker Ruth E. , Simpson Matthew J.
Published: December 2020

Mathematical models are routinely calibrated to experimental data, with goals ranging from building predictive models to quantifying parameters that cannot be measured. Whether or not reliable parameter estimates are obtainable from the available data can easily be overlooked. Such issues ofparameter identifiabilityhave important ramifications for both the predictive power of a model, and the mechanistic insight that can be obtained. Identifiability analysis is well-established for deterministic, ordinary differential equation (ODE) models, but there are no commonly adopted methods for analysing identifiability in stochastic models. We provide an accessible introduction to identifiability analysis and demonstrate how existing ideas for analysis of ODE models can be applied to stochastic differential equation (SDE) models through four practical case studies. To assessstructural identifiability, we study ODEs that describe the statistical moments of the stochastic process using open-source software tools. Using practically motivated synthetic data and Markov chain Monte Carlo methods, we assess parameter identifiability in the context of available data. Our analysis shows that SDE models can often extract more information about parameters than deterministic descriptions. All code used to perform the analysis is available onGithub.
Complexity and critical thresholds in the dynamics of visceral leishmaniasis
Authors: Bilal Shakir , Caja Rivera Rocio , Mubayi Anuj , Michael Edwin
Published: December 2020

We study a general multi-host model of visceral leishmaniasis including both humans and animals, and where host and vector characteristics are captured via host competence along with vector biting preference. Additionally, the model accounts for spatial heterogeneity in human population and heterogeneity in biting behaviour of sandflies. We then use parameters for visceral leishmaniasis in the Indian subcontinent as an example and demonstrate that the model exhibits backward bifurcation, i.e. it has a human infection and a sandfly population threshold, characterized by a bi-stable region. These thresholds shift as a function of host competence, host population size, vector feeding preference, spatial heterogeneity, biting heterogeneity and control efforts. In particular, if control is applied through human treatment a new and lower human infection threshold is created, making elimination difficult to achieve, before eventually the human infection threshold no longer exists, making it impossible to control the disease by only reducing the infection levels below a certain threshold. A better strategy would be to reduce the human infection below a certain threshold potentially by early diagnosis, control animal population levels and keep the vector population under check. Spatial heterogeneity in human populations lowers the overall thresholds as a result of weak migration between patches.
Three-dimensional segmentation of computed tomography data using
Drishti Paint
: new tools and developments
Authors: Hu Yuzhi , Limaye Ajay , Lu Jing
Published: December 2020

Computed tomography (CT) has become very widely used in scientific and medical research and industry for its non-destructive and high-resolution means of detecting internal structure. Three-dimensional segmentation of computed tomography data sheds light on internal features of target objects. Three-dimensional segmentation of CT data is supported by various well-established software programs, but the powerful functionalities and capabilities of open-source software have not been fully revealed. Here, we present a new release of the open-source volume exploration, rendering and three-dimensional segmentation software,
Drishti
v. 2.7. We introduce a new tool for thresholding volume data (i.e. gradient thresholding) and a protocol for performing three-dimensional segmentation using the 3D Freeform Painter tool. These new tools and workflow enable more accurate and precise digital reconstruction, three-dimensional modelling and three-dimensional printing results. We use scan data of a fossil fish as a case study, but our procedure is widely applicable in biological, medical and industrial research.
Data-driven strategies for optimal bicycle network growth
Authors: Natera Orozco Luis Guillermo , Battiston Federico , Iñiguez Gerardo , Szell Michael
Published: December 2020

Urban transportation networks, from pavements and bicycle paths to streets and railways, provide the backbone for movement and socioeconomic life in cities. To make urban transport sustainable, cities are increasingly investing to develop their bicycle networks. However, it is yet unclear how to extend them comprehensively and effectively given a limited budget. Here we investigate the structure of bicycle networks in cities around the world, and find that they consist of hundreds of disconnected patches, even in cycling-friendly cities like Copenhagen. To connect these patches, we develop and apply data-driven, algorithmic network growth strategies, showing that small but focused investments allow to significantly increase the connectedness and directness of urban bicycle networks. We introduce two greedy algorithms to add the most critical missing links in the bicycle network focusing on connectedness, and show that they outmatch both a random approach and a baseline minimum investment strategy. Our computational approach outlines novel pathways from car-centric towards sustainable cities by taking advantage of urban data available on a city-wide scale. It is a first step towards a quantitative consolidation of bicycle infrastructure development that can become valuable for urban planners and stakeholders.
Increased sperm production linked to competition in the maternal social environment
Authors: Hobson Liane , Hurst Jane L. , Stockley Paula
Published: December 2020

Maternal or early life effects may prepare offspring for similar social conditions to those experienced by their mothers. For males, the ability to achieve mating and fertilization success is a key social challenge. Competitive conditions may therefore favour increased body size or ejaculate production in male offspring. We tested this experimentally by comparing reproductive traits of adult male bank voles (Myodes glareolus), whose mothers had experienced contrasting encounter regimes with female conspecifics while breeding. We found that daily sperm production rates and epididymis mass were significantly higher when dams had experienced more frequent encounters with female conspecifics. This response to maternal and early life experience was specific to sperm production and storage, with no evidence for effects on male body mass or the size of testes and accessory reproductive glands. Our findings reveal a potentially adaptive effect of maternal and early life experience on the development of sperm production, which is worthy of wider investigation.
Modelling foam improved oil recovery: towards a formulation of pressure-driven growth with flow reversal
Authors: Eneotu M. , Grassia P.
Published: December 2020

The pressure-driven growth model that describes the two-dimensional (2-D) propagation of a foam through an oil reservoir is considered as a model for surfactant-alternating-gas improved oil recovery. The model assumes a region of low mobility, finely textured foam at the foam front where injected gas meets liquid. The net pressure driving the foam is assumed to reduce suddenly at a specific time. Parts of the foam front, deep down near the bottom of the front, must then backtrack, reversing their flow direction. Equations for one-dimensional fractional flow, underlying 2-D pressure-driven growth, are solved via the method of characteristics. In a diagram of position versus time, the backtracking front has a complex double fan structure, with two distinct characteristic fans interacting. One of these characteristic fans is a reflection of a fan already present in forward flow mode. The second fan however only appears upon flow reversal. Both fans contribute to the flow’s Darcy pressure drop, the balance of the pressure drop shifting over time from the first fan to the second. The implications for 2-D pressure-driven growth are that the foam front has even lower mobility in reverse flow mode than it had in the original forward flow case.
The phantom chorus: birdsong boosts human well-being in protected areas
Authors: Ferraro Danielle M. , Miller Zachary D. , Ferguson Lauren A. , Taff B. Derrick , Barber Jesse R. , Newman Peter , Francis Clinton D.
Published: December 2020

Spending time in nature is known to benefit human health and well-being, but evidence is mixed as to whether biodiversity or perceptions of biodiversity contribute to these benefits. Perhaps more importantly, little is known about the sensory modalities by which humans perceive biodiversity and obtain benefits from their interactions with nature. Here, we used a ‘phantom birdsong chorus' consisting of hidden speakers to experimentally increase audible birdsong biodiversity during ‘on' and ‘off' (i.e. ambient conditions) blocks on two trails to study the role of audition in biodiversity perception and self-reported well-being among hikers. Hikers exposed to the phantom chorus reported higher levels of restorative effects compared to those that experienced ambient conditions on both trails; however, increased restorative effects were directly linked to the phantom chorus on one trail and indirectly linked to the phantom chorus on the other trail through perceptions of avian biodiversity. Our findings add to a growing body of evidence linking mental health to nature experiences and suggest that audition is an important modality by which natural environments confer restorative effects. Finally, our results suggest that maintaining or improving natural soundscapes within protected areas may be an important component to maximizing human experiences.
Nests in the cities: adaptive and non-adaptive phenotypic plasticity and convergence in an urban bird
Authors: Bressler Samuel A. , Diamant Eleanor S. , Tingley Morgan W. , Yeh Pamela J.
Published: December 2020

Phenotypic plasticity plays a critical role in adaptation to novel environments. Behavioural plasticity enables more rapid responses to unfamiliar conditions than evolution by natural selection. Urban ecosystems are one such novel environment in which behavioural plasticity has been documented. However, whether such plasticity is adaptive, and if plasticity is convergent among urban populations, is poorly understood. We studied the nesting biology of an ‘urban-adapter’ species, the dark-eyed junco (
Junco hyemalis
), to understand the role of plasticity in adapting to city life. We examined (i) whether novel nesting behaviours are adaptive, (ii) whether pairs modify nest characteristics in response to prior outcomes, and (iii) whether two urban populations exhibit similar nesting behaviour. We monitored 170 junco nests in urban Los Angeles and compared our results with prior research on 579 nests from urban San Diego. We found that nests placed in ecologically novel locations (off-ground and on artificial surfaces) increased fitness, and that pairs practiced informed re-nesting in site selection. The Los Angeles population more frequently nested off-ground than the San Diego population and exhibited a higher success rate. Our findings suggest that plasticity facilitates adaptation to urban environments, and that the drivers behind novel nesting behaviours are complex and multifaceted.
Evolutionary fine-tuning of background-matching camouflage among geographical populations in the sandy beach tiger beetle
Authors: Yamamoto Nayuta , Sota Teiji
Published: December 2020

Background-matching camouflage is a widespread adaptation in animals; however, few studies have thoroughly examined its evolutionary process and consequences. The tiger beetleChaetodera laetescriptaexhibits pronounced variation in elytral colour pattern among sandy habitats of different colour in the Japanese Archipelago. In this study, we performed digital image analysis with avian vision modelling to demonstrate that elytral luminance, which is attributed to proportions of elytral colour components, is fine-tuned to match local backgrounds. Field predation experiments with model beetles showed that better luminance matching resulted in a lower attack rate and corresponding lower mortality. Using restriction site-associated DNA (RAD) sequence data, we analysed the dispersal and evolution of colour pattern across geographical locations. We found that sand colour matching occurred irrespective of genetic and geographical distances between populations, suggesting that locally adapted colour patterns evolved after the colonization of these habitats. Given that beetle elytral colour patterns presumably have a quantitative genetic basis, our findings demonstrate that fine-tuning of background-matching camouflage to local habitat conditions can be attained through selection by visual predators, as predicted by the earliest proponent of natural selection.
Habitat fragmentation shapes natal dispersal and sociality in an Afrotropical cooperative breeder
Authors: Cousseau Laurence , Hammers Martijn , Van de Loock Dries , Apfelbeck Beate , Githiru Mwangi , Matthysen Erik , Lens Luc
Published: December 2020

It remains poorly understood how effects of anthropogenic activity, such as large-scale habitat fragmentation, impact sociality in animals. In cooperatively breeding species, groups are mostly formed through delayed offspring dispersal, and habitat fragmentation can affect this process in two opposite directions. Increased habitat isolation may increase dispersal costs, promoting delayed dispersal. Alternatively, reduced patch size and quality may decrease benefits of philopatry, promoting dispersal. Here, we test both predictions in a cooperatively breeding bird (placid greenbul,Phyllastrephus placidus) from an Afrotropical cloud forest archipelago. Males born in fragmented forest dispersed about 1 year earlier than those born in continuous forest. Contrary to females, males also started to reproduce earlier and mostly settled within their natal patch. Females only rarely delayed their dispersal for more than 1 year, both in fragmented and continuous forests. Our results suggest that early male dispersal and reproduction is jointly driven by a decrease in the value of the natal territory and an increase in local breeding opportunities in fragmented forest. While plasticity in dispersal strategies of cooperative breeders in response to anthropogenic change is believed to optimize reproduction-survival trade-offs, to what extent it shapes the ability of species to respond to rapid environmental change remains to be studied.
Breeding season length predicts duet coordination and consistency in Neotropical wrens (Troglodytidae)
Authors: Keenan Emily L. , Odom Karan J. , Araya-Salas Marcelo , Horton Kyle G. , Strimas-Mackey Matthew , Meatte Megan A. , Mann Nigel I. , Slater Peter J. B. , Price J. Jordan , Templeton Christopher N.
Published: December 2020

Many animals produce coordinated signals, but few are more striking than the elaborate male–female vocal duets produced by some tropical songbirds. Yet, little is known about the factors driving the extreme levels of vocal coordination between mated pairs in these taxa. We examined evolutionary patterns of duet coordination and their potential evolutionary drivers in Neotropical wrens (Troglodytidae), a songbird family well known for highly coordinated duets. Across 23 wren species, we show that the degree of coordination and precision with which pairs combine their songs into duets varies by species. This includes some species that alternate their song phrases with exceptional coordination to produce rapidly alternating duets that are highly consistent across renditions. These highly coordinated, consistent duets evolved independently in multiple wren species. Duet coordination and consistency are greatest in species with especially long breeding seasons, but neither duet coordination nor consistency are correlated with clutch size, conspecific abundance or vegetation density. These results suggest that tightly coordinated duets play an important role in mediating breeding behaviour, possibly by signalling commitment or coalition of the pair to mates and other conspecifics.
Vocal convergence in a multi-level primate society: insights into the evolution of vocal learning
Authors: Fischer Julia , Wegdell Franziska , Trede Franziska , Dal Pesco Federica , Hammerschmidt Kurt
Published: December 2020

The extent to which nonhuman primate vocalizations are amenable to modification through experience is relevant for understanding the substrate from which human speech evolved. We examined the vocal behaviour of Guinea baboons,Papio papio, ranging in the Niokolo Koba National Park in Senegal. Guinea baboons live in a multi-level society, with units nested within parties nested within gangs. We investigated whether the acoustic structure of grunts of 27 male baboons of two gangs varied with party/gang membership and genetic relatedness. Males in this species are philopatric, resulting in increased male relatedness within gangs and parties. Grunts of males that were members of the same social levels were more similar than those of males in different social levels (N= 351 dyads for comparison within and between gangs, andN= 169 dyads within and between parties), but the effect sizes were small. Yet, acoustic similarity did not correlate with genetic relatedness, suggesting that higher amounts of social interactions rather than genetic relatedness promote the observed vocal convergence. We consider this convergence a result of sensory–motor integration and suggest this to be an implicit form of vocal learning shared with humans, in contrast to the goal-directed and intentional explicit form of vocal learning unique to human speech acquisition.
Negative density-dependent parasitism in a group-living carnivore
Authors: Albery Gregory F. , Newman Chris , Ross Julius Bright , MacDonald David W. , Bansal Shweta , Buesching Christina
Published: December 2020

Animals living at high population densities commonly experience greater exposure to disease, leading to increased parasite burdens. However, social animals can benefit immunologically and hygienically from cooperation, and individuals may alter their socio-spatial behaviour in response to infection, both of which could counteract density-related increases in exposure. Consequently, the costs and benefits of sociality for disease are often uncertain. Here, we use a long-term study of a wild European badger population (
Meles meles
) to investigate how within-population variation in host density determines infection with multiple parasites. Four out of five parasite taxa exhibited consistent spatial hotspots of infection, which peaked among badgers living in areas of low local population density. Combined movement, survival, spatial and social network analyses revealed that parasite avoidance was the likely cause of this negative density dependence, with possible roles for localized mortality, encounter-dilution effects, and micronutrient-enhanced immunity. These findings demonstrate that animals can organize their societies in space to minimize parasite infection, with important implications for badger behavioural ecology and for the control of badger-associated diseases.
Assessment of coral restoration’s contribution to reef recovery using machine learning
Authors: Morand Gaétan , Dixon Simon , Berre Thomas Le
Published: December 2020

Coral restoration emerged globally as a form of life support for coral reefs, awaiting urgent mitigation of anthropogenic pressure. Yet its efficiency is difficult to assess, as ambitious transplantation programs handle hundreds of thousands of fragments, with survival rates inherently time-intensive to monitor. Due to limited available data, the influence of most environmental and methodological factors is still unknown.

We therefore propose a new method which leverages machine learning to track each colony’s individual health and growth on a large sample size. This is the first time artificial intelligence techniques were used to monitor coralat a colony scale, providing an unprecedented amount of data on coral health and growth. Here we show the influence of genus, depth and initial fragment size, alongside providing an outlook on coral restoration’s efficiency.

We show that among 77,574 fragments, individual survival rate was 31% after 2 years (21% after 4 years), which is much lower than most reported results. In the absence of significant anthropogenic pressure, we showed that there was a depth limit below whichPocilloporafragments outperformedAcroporafragments, while the opposite was true past this threshold. During the mid-2019 heatwave, our research indicates thatPocilloporafragments were 37% more likely to survive thanAcroporafragments.

Overall, the total amount of live coral steadily increased over time, by more than 3,700 liters a year, as growth compensated for mortality. This supports the use of targeted coral restoration to accelerate reef recovery after mass bleaching events.
TheUstilago hordei-barley interaction is a versatile system to characterize fungal effectors
Authors: Ökmen Bilal , Schwammbach Daniela , Bakkeren Guus , Neumann Ulla , Doehlemann Gunther
Published: December 2020

Obligate biotrophic fungal pathogens, such asBlumeria graminisandPuccinia graminis, are amongst the most devastating plant pathogens, causing dramatic yield losses in many economically important crops worldwide. However, a lack of reliable tools for the efficient genetic transformation has hampered studies into the molecular basis of their virulence/pathogenicity. In this study, we present theU. hordei-barley pathosystem as a model to characterize effectors from different plant pathogenic fungi. We have generatedU. hordeisolopathogenic strains, which form infectious filaments without presence of compatible mating partner. Solopathogenic strains are suitable as heterologous expression system for fungal virulence factors. A highly efficient Crispr/Cas9 gene editing system is made available forU. hordei. In addition,U. hordeiinfection structures during barley colonization were analyzed by transmission electron microscopy, which shows thatU. hordeiforms intracellular infection structures sharing high similarity to haustoria formed by obligate rust and powdery mildew fungi. Thus,U. hordeihas high potential as a fungal expression platform for functional studies of heterologous effector proteins in barley.
The ages of zone of proximal development for retrospective time assessment and anticipation of time event
Authors: Portnova G.V. , Rebreikina A. B. , Martynova O.V.
Published: December 2020

We aimed to investigate the ability of children aged 5–14 years old (preschoolers, primary schoolers, and preteens) to assess and anticipate time intervals. 287 Russian children aged 5–14 years old and 26 adults of control group participated in our study. The neuropsychological assessment, Wechsler Intelligence Scale for Children and a battery of time-related tests were applied. All groups of children overestimated the event’s duration, although the accuracy of the second estimations increased among the participants aged 6–8 years after a prompt was offered. A zone of proximal development for time anticipation task was detected for children aged 9-11 years, when the prompt could significantly improve the accuracy of time perception. The participants overestimated the duration of both upcoming and past events, with the degree of overestimation being found to be negatively correlated with age. Further, a higher degree of accuracy in terms of time estimation was found to be correlated with higher scores on the attention and memory tests, and accuracy of time anticipation was associated with scores of praxis test.
A broad exome study of the genetic architecture of asthma reveals novel patient subgroups
Authors: Cameron-Christie Sophia , Mackay Alex , Wang Quanli , Olsson Henric , Angermann Bastian , Lassi Glenda , Lindgren Julia , Hühn Michael , Ohne Yoichiro , Gavala Monica , Wang Jingya , Povysil Gundula , Deevi Sri V. V. , Belfield Graham , Dillmann Inken , Muthas Daniel , Cohen Suzanne , Young Simon , Platt Adam , Petrovski Slavé
Published: December 2020

Introduction

Asthma risk is a complex interplay between genetic susceptibility and environment. Despite many significantly-associated common variants, the contribution of rarer variants with potentially greater effect sizes has not been as extensively studied. We present an exome-based study adopting 24,576 cases and 120,530 controls to assess the contribution of rare protein-coding variants to the risk of early-onset or all-comer asthma.

Methods

We performed case-control analyses on three genetic units: variant-, gene- and pathway-level, using sequence data from the Scandinavian Asthma Genetic Study and UK Biobank participants with asthma. Cases were defined as all-comer asthma (n=24,576) and early-onset asthma (n=5,962). Controls were 120,530 UK Biobank participants without reported history of respiratory illness.

Results

Variant-level analyses identified statistically significant variants at moderate-to-common allele frequency, including protein-truncating variants inFLGandIL33.Asthma risk was significantly increased not only by individual, commonFLGprotein-truncating variants, but also among the collection of rare-to-privateFLGprotein-truncating variants (p=6.8×10−7). This signal was driven by early-onset asthma and did not correlate with circulating eosinophil levels. In contrast, a single splice variant inIL33was significantly protective (p=8.0×10−10), while the collection of remainingIL33protein-truncating variants showed no class effect (p=0.54). A pathway-based analysis identified that protein-truncating variants in loss-of-function intolerant genes were significantly enriched among individuals with asthma.

Conclusions

Access to the full allele frequency spectrum of protein-coding variants provides additional clarity about the potential mechanisms of action forFLGandIL33.Beyond these two significant drivers, we detected a significant enrichment of protein-truncating variants in loss-of-function intolerant genes.
Choosing priors in Bayesian ecological models by simulating from the prior predictive distribution
Authors: Wesner Jeff S. , Pomeranz Justin P.F.
Published: December 2020

Bayesian data analysis is increasingly used in ecology, but prior specification remains focused on choosing non-informative priors (e.g., flat or vague priors). One barrier to choosing more informative priors is that priors must be specified on model parameters (e.g., intercepts, slopes, sigmas), but prior knowledge often exists on the level of the response variable. This is particularly true for common models in ecology, like generalized linear mixed models, which may have a link function and dozens of parameters, each of which needs a prior distribution. We suggest that this difficulty can be overcome by simulating from the prior predictive distribution and visualizing the results on the scale of the response variable. In doing so, some common choices for non-informative priors on parameters can easily be seen to produce biologically impossible values of response variables. Such implications of prior choices are difficult to foresee without visualization. We demonstrate a workflow for prior selection using simulation and visualization with two ecological examples (predator-prey body sizes and spider responses to food competition). This approach is not new, but its adoption by ecologists will help to better incorporate prior information in ecological models, thereby maximizing one of the benefits of Bayesian data analysis.
Fast and effective protein model refinement by deep graph neural networks
Authors: Jing Xiaoyang , Xu Jinbo
Published: December 2020

Protein structure prediction has been greatly improved, but there are still a good portion of predicted models that do not have very high quality. Protein model refinement is one of the methods that may further improve model quality. Nevertheless, it is very challenging to refine a protein model towards better quality. Currently the most successful refinement methods rely on extensive conformation sampling and thus, take hours or days to refine even a single protein model. Here we propose a fast and effective method that may refine protein models with very limited conformation sampling. Our method applies GNN (graph neural networks) to predict refined inter-atom distance probability distribution from an initial model and then rebuilds the model using the predicted distance as restraints. On the CASP13 refinement targets our method may refine models with comparable quality as the two leading human groups (Feig and Baker) and greatly outperforms the others. On the CASP14 refinement targets our method is only second to Feig’s method, comparable to Baker’s method and much better than the others (who worsened instead of improved model quality). Our method achieves this result by generating only 5 refined models for an initial model, which can be done in ∼15 minutes. Our study also shows that GNN performs much better than convolutional residual neural networks for protein model refinement when conformation sampling is limited.

Availability

The code will be released once the manuscript is published and available athttp://raptorx.uchicago.edu

Contact

jinboxu@gmail.com
Plasmodesmata-dependent intercellular movement of bacterial effectors
Authors: Li Zhongpeng , Variz Haris , Chen Yani , Liu Su-Ling , Aung Kyaw
Published: December 2020

Pathogenic microorganisms deliver protein effectors into host cells to suppress host immune responses. Recent findings reveal that phytopathogens manipulate the function of plant cell-to-cell communication channels plasmodesmata (PD) to promote diseases. Several bacterial and filamentous pathogen effectors have been shown to regulate PD in their host cells. A few effectors of filamentous pathogens have been reported to move from the infected cells to neighboring plant cells through PD; however, it is unclear whether bacterial effectors can traffic through PD in plants. In this study, we systemically determined the intercellular movement ofPseudomonas syringaepv.tomato(Pst) DC3000 effectors between adjoining plant cells inNicotiana benthamiana. We observed that at least 16PstDC3000 effectors move from transformed cells to the surrounding plant cells. The movement of the effectors is largely dependent on their molecular weights. The expression of PD regulators, Arabidopsis PD-located protein PDLP5 and PDLP7, lead to PD closure and inhibits the PD-dependent movement of a bacterial effector inN. benthamiana. Similarly, a 22-amino acid peptide of bacterial flagellin (flg22) treatment induces PD closure and suppresses the movement of a bacterial effector inN. benthamiana. Together, our findings demonstrated that bacterial effectors are able to move intercellularly through PD in plants.
Manual Annotation of Genes withinDrosophilaSpecies: the Genomics Education Partnership protocol
Authors: Rele Chinmay P. , Sandlin Katie M. , Leung Wilson , Reed Laura K.
Published: December 2020

Annotating the genomes of multiple organisms allows us to study their genes as well as the evolution of those genes. While many eukaryotic genome assemblies already include computational gene predictions, these predictions can benefit from review and refinement through manual gene annotation. The Genomics Education Partnership (GEP;thegep.org) has developed an annotation protocol for protein-coding genes that enables undergraduate students and other researchers to create high-quality gene annotations that can be utilized in subsequent scientific investigations. For example, this protocol has been utilized by the GEP faculty to engage undergraduate students in the comparative annotation of genes involved in the insulin signaling pathway in 28Drosophilaspecies, usingD. melanogasteras the informant genome. Students construct gene models using multiple lines of computational and experimental evidence including expression data (e.g., RNA-Seq), sequence similarity (e.g., BLAST, multiple sequence alignments), and computational gene predictions. For quality control, each gene is annotated by at least two students working independently, followed by reconciliation of the submitted gene models by a more experienced student. This article provides an overview of the annotation protocol and describes how discrepancies in student submitted gene models are resolved to produce a final, high-quality gene set suitable for subsequent analyses. This annotation protocol can be adapted to other scientific questions (e.g., expansion of theDrosophilaMuller F element) and other species (e.g., parasitoid wasps) to provide additional opportunities for undergraduate students to participate in genomics research. These student annotation efforts can substantially improve the quality of gene annotations in publicly available genomic databases.
BBrowser: Making single-cell data easily accessible
Authors: Le Tri , Phan Tan , Pham Minh , Tran Dat , Lam Loc , Nguyen Tung , Truong Thao , Vuong Hy , Luu Tam , Phung Nam , Pham Ngan , Nguyen Trang , Pham Oanh , Nguyen An , Nguyen Huy , Tran Hao , Tran Loc , Nguyen Ha An , Tran Thanh , Nguyen Nhung , Tran Ngoc , Boysen Cecilie , Nguyen Uyen , Pham Vy , Kim Theodore , Pham Ngoc , Gill Tristan , Pham Son
Published: December 2020

BioTuring’s BBrowser is a software solution that helps scientists effectively analyze single-cell omics data. It combines big data with big computation and modern data visualization to create a unique platform where scientists can interact and obtain important biological insights from the massive amounts of single-cell data. BBrowser has three main components: a curated single-cell database, a big-data analytics layer, and a data visualization module. BBrowser is available for download at:https://bioturing.com/bbrowser/download.
Profound Treg perturbations correlate with COVID-19 severity
Authors: Galván-Peña Silvia , Leon Juliette , Chowdhary Kaitavjeet , Michelson Daniel A. , Vijaykumar Brinda , Yang Liang , Magnuson Angela , Manickas-Hill Zachary , Piechocka-Trocha Alicja , Worrall Daniel P. , Hall Kathryn E. , Ghebremichael Musie , Walker Bruce D. , Li Jonathan Z. , Yu Xu G. ,   MGH COVID-19 Collection & Processing Team, Mathis Diane , Benoist Christophe
Published: December 2020

The hallmark of severe COVID-19 disease has been an uncontrolled inflammatory response, resulting from poorly understood immunological dysfunction. We explored the hypothesis that perturbations in FoxP3+ T regulatory cells (Treg), key enforcers of immune homeostasis, contribute to COVID-19 pathology. Cytometric and transcriptomic profiling revealed a distinct Treg phenotype in severe COVID-19 patients, with an increase in both Treg proportions and intracellular levels of the lineage-defining transcription factor FoxP3, which correlated with poor outcomes. Accordingly, these Tregs over-expressed a range of suppressive effectors, but also pro-inflammatory molecules like IL32. Most strikingly, they acquired similarity to tumor-infiltrating Tregs, known to suppress local anti-tumor responses. These traits were most marked in acute patients with severe disease, but persisted somewhat in convalescent patients. These results suggest that Tregs may play nefarious roles in COVID-19, via suppressing anti-viral T cell responses during the severe phase of the disease, and/or via a direct pro-inflammatory role.
Distinct expression of select and transcriptome-wide isolated 3’UTRs suggests critical roles in development and transition states
Authors: Ji Shaoyi , Yang Ze , Gozali Leonardi , Kenney Thomas , Kocabas Arif , Park Carolyn Jinsook , Hynes Mary
Published: December 2020

Mature mRNA molecules are typically considered to be comprised of a 5’UTR, a 3’UTR and a coding region (CDS), all attached until degradation. Unexpectedly, however, there have been multiple recent reports of widespread differential expression of mRNA 3’UTRs and their cognate coding regions, resulting in the expression of isolated 3’UTRs (i3’UTRs); these i3’UTRs can be highly expressed, often in reciprocal patterns to their cognate CDS. Similar to the role of other lncRNAs, isolated 3’UTRs are likely to play an important role in gene regulation but little is known about the contexts in which they are deployed. To begin to parse the functions of i3’UTRs, here we carry outin vitro, in vivoandin silicoanalyses of differential 3’UTR/CDS mRNA ratio usage across tissues, development and cell state changes both for a select list of developmentally important genes as well as through unbiased transcriptome-wide analyses. Across two developmental paradigms we find a distinct switch from high i3’UTR expression of stem cell related genes in proliferating cells compared to newly differentiated cells. Our unbiased transcriptome analysis across multiple gene sets shows that regardless of tissue, genes with high 3’UTR to CDS ratios belong predominantly to gene ontology categories related to cell-type specific functions while in contrast, the gene ontology categories of genes with low 3’UTR to CDS ratios are similar and relate to common cellular functions. In addition to these specific findings our data provide critical information from which detailed hypotheses for individual i3’UTRs can be tested-with a common theme that i3’UTRs appear poised to regulate cell-specific gene expression and state.

Significance Statement

The widespread existence and expression of mRNA 3’ untranslated sequences in the absence of their cognate coding regions (called isolated 3’UTRs or i3’UTRs) opens up considerable avenues for gene regulation not previously envisioned. Each isolated 3’UTR may still bind and interact with micro RNAs, RNA binding proteins as well as other nucleic acid sequences, all in the absence or low levels of cognate protein production. Here we document the expression, localization and regulation of i3’UTRs both within particular biological systems as well as across the transcriptome. As this is an entirely new area of experimental investigation these early studies are seminal to this burgeoning field.
16p12.1 deletion orthologs are expressed in motile neural crest cells and are important for regulating craniofacial development inXenopus laevis
Authors: Lasser Micaela , Bolduc Jessica , Murphy Luke , O’Brien Caroline , Lee Sangmook , Girirajan Santhosh , Lowery Laura Anne
Published: December 2020

Copy number variants (CNVs) associated with neurodevelopmental disorders are characterized by extensive phenotypic heterogeneity. In particular, one CNV was identified in a subset of children clinically diagnosed with intellectual disabilities (ID) that results in a hemizygous deletion of multiple genes at chromosome 16p12.1. In addition to ID, individuals with this deletion display a variety of symptoms including microcephaly, seizures, cardiac defects, and growth retardation. Moreover, patients also manifest severe craniofacial abnormalities, such as micrognathia, cartilage malformation of the ears and nose, and facial asymmetries; however, the function of the genes within the 16p12.1 region have not been studied in the context of vertebrate craniofacial development. The craniofacial tissues affected in patients with this deletion all derive from the same embryonic precursor, the cranial neural crest, leading to the hypothesis that one or more of the 16p12.1 genes may be involved in regulating neural crest cell (NCC)-related processes. To examine this, we characterized the developmental role of the 16p12.1-affected gene orthologs,polr3e,mosmo,uqcrc2, andcdr2, during craniofacial morphogenesis in the vertebrate model system,Xenopus laevis. While the currently-known cellular functions of these genes are diverse, we find that they share similar expression patterns along the neural tube, pharyngeal arches, and later craniofacial structures. As these genes show co-expression in the pharyngeal arches where NCCs reside, we sought to elucidate the effect of individual gene depletion on craniofacial development and NCC migration. We find that reduction of several 16p12.1 genes significantly disrupts craniofacial and cartilage formation, pharyngeal arch migration, as well as NCC specification and motility. Thus, we have determined that some of these genes play an essential role during vertebrate craniofacial patterning by regulating specific processes during NCC development, which may be an underlying mechanism contributing to the craniofacial defects associated with the 16p12.1 deletion.
The molecular basis, genetic control and pleiotropic effects of local gene co-expression
Authors: Ribeiro Diogo M. , Rubinacci Simone , Ramisch Anna , Hofmeister Robin J. , Dermitzakis Emmanouil T. , Delaneau Olivier
Published: December 2020

Nearby genes are often expressed as a group. Yet, the prevalence, molecular mechanisms and genetic control of local gene co-expression are far from being understood. Here, by leveraging gene expression measurements across 49 human tissues and hundreds of individuals, we found that local gene co-expression occurs in 13% to 53% genes per tissue. By integrating various molecular assays (e.g. ChIP-seq and Hi-C), we estimated the ability of several mechanisms, such as enhancer-gene targeting, in distinguishing gene pairs that are co-expressed from those that are not. Notably, we identified 32,636 expression quantitative trait loci (eQTLs) which associate to co-expressed gene pairs and often overlap enhancer regions. Due to affecting several genes, these eQTLs are more often associated with multiple human traits than other eQTLs. Our extensive search for local gene co-expression opens the way to comprehend trait pleiotropy and comorbidity and provide functional interpretation of QTL and GWAS findings.