bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the distribution of phylogenetic networks generated under a birth-death-hybridization process
Authors: Justison Joshua A. , Heath Tracy A. 
Published: November 2022

ABSTRACTGene-flow processes such as hybridization and introgression play important roles in shaping diversity across the tree of life. Recent studies extending birth-death models have made it possible to investigate patterns of reticulation in a macroevolutionary context. These models allow for different macroevolutionary patterns of gene flow events that can either add, maintain, or remove lineages—with the gene flow itself possibly being dependent on the relatedness between species—thus creating complex diversification scenarios. Further, many reticulate phylogenetic inference methods assume specific reticulation structures or phylogenies belonging to certain network classes. However, the distributions of phylogenetic networks under reticulate birth-death processes are poorly characterized, and it is unknown whether they violate common methodological assumptions. We use simulation techniques to explore phylogenetic network space under a birth-death-hybridization process where the hybridization rate can have a linear dependence on genetic distance. Specifically, we measured the number of lineages through time and role of hybridization in diversification along with the proportion of phylogenetic networks that belong to commonly used network classes (e.g., tree-child, tree-based, or level-1 networks). We find that the growth of phylogenetic networks and class membership are largely affected by assumptions about macroevolutionary patterns of gene flow. In accordance with previous studies, a lower proportion of networks belonged to these classes based on type and density of reticulate events. However, under a birth-death-hybridization process, these factors form an antagonistic relationship; the type of reticulation events that cause high membership proportions also lead to the highest reticulation density, consequently lowering the overall proportion of phylogenies in some classes. Further, we observed that genetic distance–dependent gene flow and incomplete sampling increase the proportion of class membership, primarily due to having fewer reticulate events. Our results can inform studies if their biological expectations of gene flow are associated with evolutionary histories that satisfy the assumptions of current methodology and aid in finding phylogenetic classes that are relevant for methods development.
Rockfish: A Transformer-based Model for Accurate 5-Methylcytosine Prediction from Nanopore Sequencing
Authors: Stanojević Dominik , Li Zhe , Foo Roger , Šikić Mile 
Published: November 2022

AbstractDNA methylation plays a crucial role in various biological processes, including cell differentiation, ageing, and cancer development. The most important methylation in mammals is 5-methylcytosine (5mC) which is present in the context of CpG dinucleotides. Sequencing methods such as whole-genome bisulfite sequencing (WGBS) successfully detect 5mC DNA modifications. However, they suffer from the serious drawbacks of short read lengths and might introduce an amplification bias. Here we present Rockfish, a deep learning algorithm that significantly improves read-level 5mC detection by using Nanopore sequencing. Compared to other methods based on Nanopore sequencing, there is an increase in the single-base accuracy and the F1 measure of up to 5% and 12%, respectively. Furthermore, Rockfish shows a high correlation with WGBS and requires lower read depth while being computationally efficient. We deem that Rockfish is broadly applicable to study 5mC methylation in diverse organisms and disease systems to yield biological insights.
Genetic and structural data on the SARS-CoV-2 Omicron BQ.1 variant reveal its low potential for epidemiological expansion
Authors: Scarpa Fabio , Sanna Daria , Benvenuto Domenico , Borsetti Alessandra , Azzena Ilenia , Casu Marco , Fiori Pier Luigi , Giovanetti Marta , Maruotti Antonello , Ceccarelli Giancarlo , Caruso Arnaldo , Caccuri Francesca , Cauda Roberto , Cassone Antonio , Pascarella Stefano , Ciccozzi Massimo 
Published: November 2022

AbstractThe BQ.1 SARS-CoV-2 variant, also known as Cerberus, is one of the most recent Omicron descendant lineages. Compared to its direct progenitor BA.5, BQ.1 carries out some additional spike mutations in some key antigenic site which confer it further immune escape ability over other circulating lineage. In such a context, here we performed a genome-based survey aimed to obtain an as complete as possible nuance of this rapidly evolving Omicron subvariant. Genetic data suggests that BQ.1 represents an evolutionary blind background, lacking of the rapid diversification which is typical of a dangerous lineage. Indeed, the evolutionary rate of BQ.1 is very similar to that of BA.5 (7.6 × 10−4and 7 × 10−4subs/site/year, respectively), which is circulating by several months. Bayesian Skyline Plot reconstruction, indicates low level of genetic variability, suggesting that the peak has been reached around September 3, 2022. Structure analyses performed by comparing the properties of BQ.1 and BA.5 RBD indicated that the impact of the BQ.1 mutations on the affinity for ACE2 may be modest. Likewise, immunoinformatic analyses showed modest differences between the BQ.1 and the BA5 potential B-cells epitope. In conclusion, genetic and structural analysis on SARS-CoV-2 BQ.1 suggest that, it does not show evidence about its particular dangerous or high expansion capability. The monitoring genome-based must continue uninterrupted for a better understanding of its descendant and all other lineages.
Comparison of phylogenetic placements to pairwise alignments for taxonomic assignment of ciliate OTUs
Authors: Ewers Isabelle , Rajter Lubomír , Czech Lucas , Mahé Frédéric , Stamatakis Alexandros , Dunthorn Micah 
Published: November 2022

AbstractTaxonomic assignment of OTUs is an important bioinformatics step in analyzing environmental sequencing data. Pairwise-alignment and phylogenetic-placement methods represent two alternative approaches to taxonomic assignments, but their results can differ. Here we used available colpodean ciliate OTUs from forest soils to compare the taxonomic assignments of VSEARCH (which performs pairwise alignments) and EPA-ng (which performs phylogenetic placements). We showed that when there are differences in taxonomic assignments between pairwise alignments and phylogenetic placements at the subtaxon level, there is a low pairwise similarity of the OTUs to the reference database. We then showcase how the output of EPA-ng can be further evaluated using GAPPA to assess the taxonomic assignments when there exist multiple equally likely placements of an OTU, by taking into account the sum over the likelihood weights of the OUT placements within a subtaxon, and the branch distances between equally likely placement locations. We also inferred evolutionary and ecological characteristics of the colpodean OTUs using their placements within subtaxa. This study demonstrates how to fully analyse the output of EPA-ng, by using GAPPA in conjunction with knowledge of the taxonomic diversity of the clade of interest.
Co-occurrence of essential gene dispensability and bypass suppressor mutations across species
Authors: Pons Carles , Leeuwen Jolanda van 
Published: November 2022

ABSTRACTGenes have been historically classified as either essential or non-essential based on their requirement for viability. However, some genes are essential in some genetic backgrounds but non-essential in others, thus challenging the binary classification of gene essentiality. Such dispensable essential genes represent a valuable model for understanding the incomplete penetrance of loss-of-function mutations that is often observed in natural populations. Here, we compiled data from multiple studies on essential gene dispensability inSaccharomyces cerevisiaeto comprehensively characterize these genes. In analyses spanning different evolutionary time-scales, ranging fromS. cerevisiaestrains to human cell lines, dispensable essential genes exhibited distinct phylogenetic properties compared to other essential and non-essential genes. Integration of interactions with suppressor genes that can bypass the gene essentiality revealed the high functional modularity of the bypass suppression network. Furthermore, dispensable essential and bypass suppressor gene pairs reflected simultaneous changes in the mutational landscape ofS. cerevisiaestrains. Importantly, species in which dispensable essential genes were non-essential tended to carry bypass suppressor mutations in their genomes. Overall, our study offers a comprehensive view of dispensable essential genes and illustrates how their interactions with bypass suppressor genes reflect evolutionary outcomes.
The CUT&RUN Blacklist of Problematic Regions of the Genome
Authors: Nordin Anna , Zambanini Gianluca , Pagella Pierfrancesco , Cantù Claudio 
Published: November 2022

AbstractCleavage Under Targets and Release Using Nuclease (CUT&RUN) is an increasingly popular technique to map genome-wide binding profiles of histone modifications, transcription factors and co-factors. The ENCODE project and others have compiled blacklists for ChIP-seq which have been widely adopted: these lists contain regions of high and unstructured signal, regardless of cell type or protein target. While CUT&RUN obtains similar results to ChIP-seq, its biochemistry and subsequent data analyses are different. We found that this results in a CUT&RUN-specific set of undesired high-signal regions. For this reason, we have compiled blacklists based on CUT&RUN data for the human and mouse genomes, identifying regions consistently called as peaks in negative controls by the CUT&RUN peak caller SEACR. Using published CUT&RUN data from our and other labs, we show that the CUT&RUN blacklist regions can persist even when peak calling is performed with SEACR against a negative control, and after ENCODE blacklist removal. Moreover, we experimentally validated the CUT&RUN Blacklists by performing reiterative negative control experiments in which no specific protein is targeted, showing that they capture >80% of the peaks identified. We propose that removing these problematic regions prior to peak calling can substantially improve the performance of SEACR-based peak calling in CUT&RUN experiments, resulting in more reliable peak datasets.
Molecular autism research in Africa: a scoping review comparing publication outputs to Brazil, India, the UK, and the USA
Authors: Frickel Emma , Bam Sophia , Buchanan Erin , Mahony Caitlyn , van der Watt Mignon , O’Ryan Colleen 
Published: November 2022

ABSTRACTThe increased awareness of autism spectrum disorders (ASD) is accompanied by burgeoning ASD research, and concerted research efforts are trying to elucidate the molecular ASD aetiology. However, much of this research is concentrated in the Global North, with recent reviews of research in Sub-Saharan Africa (SSA) highlighting the significant shortage of ASD publications from this region. The most limited focus area was molecular research with only two molecular studies ever published from SSA, both being from South Africa (SA). We examine the molecular ASD research publications from 2016 to 2021 from all African countries, with a special focus on SA. The SSA publications are compared to Brazil and India, two non-African, low-to-middle-income countries (LMICs), and to the UK and USA, two high-income countries (HICs). There were 228 publications across all regions of interest; only three publications were from SA. Brazil (n=29) and India (n=27) had almost 10 times more publications than SA. The HICs had more publications than the LMICs, with the UK (n=62) and the USA (n=74) having approximately 20 to 25 times more publications than SA, respectively. Given that SA has substantial research capacity as demonstrated by its recent research on SARS-CoV-2, we explore potential reasons for this deficit in molecular ASD publications from SA. We compare mental health research outputs, GDP per capita, research and development expenditure, and the number of psychiatrists and child psychiatrists per 100,000 people across all regions. The UK and the USA had significantly higher numbers for all these indicators, consistent with their higher publication output. Among the LMICs, SA can potentially produce more molecular ASD research, however, there are numerous barriers that need to be addressed to facilitate increased research capacity. These include cultural stigmas, challenges in accessing mental healthcare, shortages of specialists in the public sector, and the unreliability of ASD diagnostic tools across the 11 official SA languages. The unique genetic architecture of African populations presents an untapped reservoir for finding novel genetic loci associated with ASD. Therefore, addressing the disparity in molecular ASD research between the Global North and SSA is integral to global advancements in ASD research.
Generative modeling of short, disordered proteins with homogeneous sequence composition
Authors: Taneja Ishan , Lasker Keren 
Published: November 2022

AbstractProtein design has seen remarkable progress in the past decade, with numerous examples ofde novoproteins with novel topologies and functions being successfully synthesized. Computational tools have played a large role in the ability to rationally design proteins. Recently, there have been numerous successes applying deep learning techniques to protein design that have demonstrated comparable or significantly improved performance over traditional energy-based approaches. However, the protein design problem has been less well explored for disordered proteins or, more generally, proteins with conformational heterogeneity. In this work, we demonstrate that if one approximates the spatial output of a coarse-grained molecular dynamics simulation as a multivariate normal distribution parameterized by a mean vector (representing an ensemble-averaged pairwise distance map) and covariance matrix, one can train a generative model to learn the distribution of these parameters across a set of sequences. Specifically, we encoded the mean vector and covariance matrix for each sequence in a low-dimensional space via a fixed linear transformation and trained a masked auto-encoder to accurately learn the distribution of this low-dimensional output. Furthermore, by sampling from the masked auto-encoder and transforming the generated samples back into their original high-dimensional space, one can generate realistic, ensemble-averaged pairwise distance maps. These results were demonstrated on coarse-grained simulation data derived from approximately 2000 distinct sequences, each sequence being 24 residues in length and consisting exclusively of glycine, serine, glutamate, and lysine. Though this set of sequences is relatively homogeneous in composition, we speculate our approach can be applied to disordered sequences of longer length and more heterogeneous composition, given the appropriate training set.
Cell adhesion molecules play subclass-specific roles in electrophysiological response and Schizophrenia risk
Authors: Li Xinzhe , Hu Hongru , Johansen Nelson , Quon Gerald 
Published: November 2022

ABSTRACTMultimodal assays such as Patch-seq that simultaneously profile molecular and cellular phenotypes of cells enable the identification of molecular underpinnings of electrophysiological response patterns in neurons. Here we analyzed Patch-seq measurements of thousands of mouse interneurons to identify subclass-specific genes associated with different electrophysiological features. We found extensive subclass specificity: even for the same ephys feature, largely unique sets of genes are associated with that feature in different subclasses. Well established ephys genes such as Reln demonstrated subclass specificity that was previously not reported. Surprisingly, we found that ion channels explained significantly less variation in ephys response across interneurons compared to other genes; in particular, gene sets enriched in cell adhesion genes were amongst the most associated. We found our gene sets associated with action potential dV/dt measurements explained significant heritability of Schizophrenia risk, suggesting a novel role of single neuron electrophysiology in Schizophrenia risk. Finally, we observed significant ephys function switching of cell adhesion molecules across subclasses; the same adhesion molecule was observed to associate with different functional ephys measurements in distinct subclasses and co-express with different genes, suggesting re-purposing of adhesion molecules in different subclasses. Overall, our results yield novel insight into the specificity of roles that individual genes and adhesion molecules play in both single neuron ephys response and Schizophrenia risk.
Clustered Cases of Human Adenovirus types 4, 7 and 14 Infections during the 2018 - 2019 Season revealed by US Department of Defense Respiratory Pathogen Surveillance and Whole Genome Sequencing
Authors: Pollio Adam R. , Fries Anthony C. , Yang Yu , Hughes Jerry J. , Fung Christian K. , Conte Matthew A. , Kuschner Robert A. , Collins Natalie D. , Macias Elizabeth A. , Hang Jun 
Published: November 2022

AbstractHuman adenoviruses (HAdV) are genetically diverse and can infect a number of tissues with severities varied from mild to fatal. HAdV types 3, 4, 7, 11, 14, 21 and 55 were associated with acute respiratory illnesses (ARI) outbreaks in the US and in other countries. The risk of outbreaks can be effectively controlled by HAdV vaccination or mitigated by screening and preventive measures. During the influenza season 2018 – 2019, the DoD Global Respiratory Pathogen Surveillance Program (DoDGRS) received 24,300 specimens. HAdV samples that produced positive cytopathic effects in viral cultivation were subjected to next-generation sequencing for genome sequence assembly, genome typing, whole genome phylogeny, and sequence comparative analyses. Variety of HAdV types were identified in this study, including HAdV types 1 – 7, 14, 55 and 56. HAdV types 4, 7 and 14 were found in clustered cases in Colorado, Florida, New York, and South Carolina. Comparative sequence analyses of these isolates revealed the emergence of novel genetic mutations despite the stability of adenovirus genomes. Genomic surveillance of HAdV related to possible outbreaks, shed light on prevalence, genetic divergence, and viral evolution of human adenoviruses. Continued surveillance will inform risk assessment and countermeasures.
Using large-scale whole-genome sequence data for single-step genomic predictions in maternal and terminal pig lines
Authors: Jang Sungbong , Ros-Freixedes Roger , Hickey John M. , Chen Ching-Yi , Herring William O. , Misztal Ignacy , Lourenco Daniela 
Published: November 2022

AbstractBackgroundWhole-genome sequence (WGS) data harbor causative variants that may not be present in the regular SNP chip data. The objective of this study was to investigate the impact of using preselected variants from WGS for single-step genomic predictions in maternal and terminal pig lines with up to 1.8k sequenced and 104k imputed sequenced animals per line.MethodsTwo maternal and four terminal lines were investigated for eight and seven traits, respectively. The number of sequenced animals ranged from 1,365 to 1,491 in maternal lines and 381 to 1,865 in terminal lines. Imputation occurred within each line, and the number of animals imputed to sequence ranged from 66k to 76k in maternal lines and 29k to 104k in terminal lines. Two preselected SNP sets were generated based on genome-wide association study (GWAS). Top40k included the SNP with the lowest p-value in each of 40k genomic windows; ChipPlusSign included significant variants integrated into the regular porcine SNP chip. Single-step genomic predictions with equal or different SNP variances using those SNP sets were compared to the regular porcine SNP chip.ResultsIn maternal lines, ChipPlusSign, and Top40k showed, on average, 0.62%, and 4.9% increased accuracy compared to the regular porcine SNP chip. The greatest changes were for fertility traits with Top40k, where the initial accuracy based on the SNP chip was low. However, for terminal lines, Top40k resulted in a loss of accuracy of 1% on average. Only ChipPlusSign provided a positive, albeit small, gain (0.85%). Assigning different variances for SNP slightly improved accuracies when using variances obtained from BayesR; however, the increase was inconsistent across the lines and traits.ConclusionsThe benefit of using sequence data depends on the line, size of the genotyped population, and how the WGS variants are preselected. When WGS is available on hundreds of thousands of animals, the advantage of sequence data is present but limited in maternal and terminal pig lines.
Epidemic control using stochastic and deterministic transmission models: performance comparison with and without parameter uncertainties
Authors: Flaig Julien , Houy Nicolas 
Published: November 2022

AbstractBackgroundThe spread of infectious diseases can be modeled using deterministic models assuming a continuous population or stochastic models assuming a discrete population. A stochastic model can be approximated by its deterministic counterpart under some conditions, however deterministic models are unable to captures effects pertaining to the discrete nature of populations, for instance epidemic extinction. We look into the choice of a model – deterministic or stochastic – from the perspective of decision making. We are interested in the influence of parameter uncertainties and of the quality of the estimates used to inform decisions.MethodWe consider an emerging disease in a closed population whose spread can be modeled by a stochastic SIR model or its deterministic version. Our objective is to minimize the cumulative number of symptomatic infected-days over the course of the epidemic by picking a vaccination policy out of three available options. We consider four decision making scenarios: based on the stochastic model or the deterministic model, and informed or under parameter uncertainty. We also consider different sample sizes covering parameter draws, stochastic model runs, or both depending on the scenario. We estimate the average performance of decision making in each scenario and for each sample size.ResultsThe model used for decision making has an influence on the picked policies. The best achievable performance is obtained with the stochastic model, knowing parameter values, and for a large sample size. For small sample sizes, the deterministic model can outperform the stochastic model due to stochastic effects, both in the informed and the uninformed cases. Starting with the deterministic model under uncertainty, resolving uncertainties brings more benefit than switching to the stochastic model in our example.ConclusionThis article illustrates the interplay between the choice of a type of model, parameter uncertainties, and sample sizes. It points to issues to be carefully considered when attempting to optimize a stochastic model.
Covid-19 in Brazil: A Cross-Sectional Immuno-Epidemical and Genomic Evaluation in a Pre-Omicron Era
Authors: de Oliveira Rodrigues Sarah , de Oliveira Gabriel Ferrari , e Silva Marcella Pâmela Costa , Pagnossa Jorge Pamplona 
Published: November 2022

ABSTRACTThe seventh human coronavirus, was discovered and reported primarily in Wuhan, China. After intense seasons with repercussions in all areas ofhumanity, the pandemic demonstrates a new perspective. In Brazil, the pandemic concept has had impacts in vast areas, including mainly hospitals. This present study aims to describe, present and synthesize data that correlate the symptoms of passive and/or active patients for Covid-19 and their respective results of igg/igm serological tests in hospitals in cruzeiro, São Paulo. The form had been applied to 333 people and obtained conclusive results and several symptoms presented, in addition, asymptomatic cases were also analyzed and directed in the genomic study of variants of concern, as well as vaccination data in the study region.