bluuebunny/crossref_metadata_2025_split huggingface dataset:
How much should we sequence? An analysis of the Swiss SARS-CoV-2 surveillance effort
Authors: Wegner Fanny , Cabrera-Gil Blanca , Araud Tanguy , Beckmann Christiane , Beerenwinkel Niko , Bertelli Claire , Carrara Matteo , Cerutti Lorenzo , Chen Chaoran , Cordey Samuel , Dumoulin Alexis , du Plessis Louis , Friedli Marc , Gerth Yannick , Greub Gilbert , Härri Adrian , Hirsch Hans , Howald Cedric , Huber Michael , Imhof Alexander , Kaiser Laurent , Kufner Verena , Leib Stephen L. , Leuzinger Karoline , Lleshi Etleva , Lucchini Gladys Martinetti , Mäusezahl Mirjam , Moraz Milo , Neher Richard , Nolte Oliver , Ramette Alban , Redondo Maurice , Risch Lorenz , Rohner Lionel , Roloff Tim , Schläpfer Pascal , Schneider Katrin , Singer Franziska , Spina Valeria , Stadler Tanja , Studer Erik , Topolsky Ivan , Trkola Alexandra , Walther Daniel , Wohlwend Nadia , Zehnder Cinzia , Neves Aitana , Egli Adrian ,   the SPSP consortium
Published: August 2023

AbstractBackgroundDuring the SARS-CoV-2 pandemic, many countries directed substantial resources towards genomic surveillance to detect and track viral variants. There is a debate over how much sequencing effort is necessary in national surveillance programs for SARS-CoV-2 and future pandemic threats.AimWe aimed to investigate the effect of reduced sequencing on surveillance outcomes in a large genomic dataset from Switzerland, comprising more than 143k sequences.MethodsWe employed a uniform downsampling strategy using 100 iterations each to investigate the effects of fewer available sequences on the surveillance outcomes: (i) first detection of variants of concern (VOCs), (ii) speed of introduction of VOCs, (iii) diversity of lineages, (iv) first cluster detection of VOCs, (v) density of active clusters, and (vi) geographic spread of clusters.ResultsThe impact of downsampling on VOC detection is disparate for the three VOC lineages, but many outcomes including introduction and cluster detection could be recapitulated even with only 35% of the original sequencing effort. The effect on the observed speed of introduction and first detection of clusters was more sensitive to reduced sequencing effort for some VOCs, in particular Omicron and Delta, respectively.ConclusionA genomic surveillance program needs a balance between societal benefits and costs. While the overall national dynamics of the pandemic could be recapitulated by a reduced sequencing effort, the effect is strongly lineage dependent – something that is unknown at the time of sequencing – and comes at the cost of accuracy, in particular for tracking the emergence of potential VOCs.
Metagenomic analysis of individual mosquitos reveals the ecology of insect viruses
Authors: Pan Yuan-fei , Zhao Hailong , Gou Qin-yu , Shi Pei-bo , Tian Jun-hua , Feng Yun , Li Kun , Yang Wei-hong , Wu De , Tang Guangpeng , Zhang Bing , Ren Zirui , Peng Shiqin , Luo Geng-yan , Le Shi-jia , Xin Gen-yang , Wang Jing , Hou Xin , Peng Min-wu , Kong Jian-bin , Chen Xin-xin , Yang Chun-hui , Mei Shi-qiang , Liao Yu-qi , Cheng Jing-xia , Wang Juan , Chaolemen  , Wu Yu-hui , Wang Jian-bo , An Tongqing , Huang Xinyi , Eden John-Sebastian , Li Jun , Guo Deyin , Liang Guodong , Jin Xin , Holmes Edward C. , Li Bo , Wang Daxi , Li Junhua , Wu Wei-chen , Shi Mang 
Published: August 2023

ABSTRACTMosquito transmitted viruses are responsible for an increasing burden of human disease. Despite this, little is known about the diversity and ecology of viruses within individual mosquito hosts. Using a meta-transcriptomic approach, we analysed the virome of 2,438 individual mosquitos (79 species), spanning ∼4000 km along latitudes and longitudes in China. From these data we identified 393 core viral species associated with mosquitos, including seven (putative) arbovirus species. We identified potential species and geographic hotspots of viral richness and arbovirus occurrence, and demonstrated that host phylogeny had a strong impact on the composition of individual mosquito viromes. Our data revealed a large number of viruses shared among mosquito species or genera, expanding our knowledge of host specificity of insect-associated viruses. We also detected multiple virus species that were widespread throughout the country, possibly facilitated by long-distance mosquito migrations. Together, our results greatly expand the known mosquito virome, linked the viral diversity at the scale of individual insects to that at a country-wide scale, and offered unique insights into the ecology of viruses of insect vectors.
Validation study for noninvasive single-cell-based prenatal genetic testing
Authors: Bellair Michelle , Amaral Elisabete , Ouren Mason , Roark Cameron , Kim Jaeweon , O’Connor April , Soriano Adrianna , Schindler Margaret L. , Wapner Ronald J. , Stone Joanne L. , Tavella Nicola , Merriam Audrey , Perley Lauren , Breman Amy M. , Beaudet Arthur L. 
Published: August 2023

AbstractObjectiveTo clinically validate a cell-based noninvasive prenatal genetic test using sequence-based copy number analysis of single trophoblasts from maternal blood.MethodsBlood was obtained from 401 individuals (8-22 weeks) and shipped overnight. Red blood cells were lysed, and nucleated cells stained for cytokeratin (CK) and CD45 using fluorescent antibodies and enriched for positive CK staining. Automated microscopic scanning was used to identify and pick single CK+/CD45-trophoblasts which were subjected to whole genome amplification and next-generation sequencing.ResultsBlood was obtained from 243 pregnancies scheduled for CVS or amniocentesis. Luna results were normal for 160 singletons while 15 cases were abnormal (14 aneuploidy and one monozygotic twin case with Williams syndrome deletion). These Luna results agreed with CVS/amniocentesis. Placental mosaicism occurred in 7 of 236 (3.0%) Luna cases and in 3 of 188 (1.6%) CVS cases (total 4.6%). No scorable trophoblasts were recovered in 32 of 236 (13.6%) usable samples. Additionally, 158 low-risk pregnancies not undergoing CVS/amniocentesis showed normal results for 133 cases. Seven had aneuploidy results, and there were 3 likely pathogenic deletions or duplications including one15q11-q13 deletion.ConclusionThis noninvasive cell-based prenatal genetic test detected aneuploidy and deletions/duplications with high sensitivity and specificity based on concordance with CVS/amniocentesis.Key pointsWhat’s already known about this topic?As a proof of principle for noninvasive genetic prenatal diagnosis, circulating fetal trophoblasts have been isolated from maternal blood and analyzed for detection of aneuploidy and genomic deletions and duplications.These trophoblasts reflect the genotype of the current placenta(s) but not necessarily the genotype of the fetus because of placental mosaicism.What does this study add?This study demonstrates the advantages of single cell analysis and the feasibility of launching a test for reliable detection of cytogenetic aneuploidy, deletions, and duplications.This test has improved detection of deletions and duplications compared to cell-free NIPT, but widespread adoption will require improved recovery of fetal cells from maternal blood and reduced cost through automation and high-throughput.
Comparative Analysis of Cytokine Profiles in Cerebrospinal Fluid and Blood Serum in Patients with Acute and Subacute Spinal Cord Injury
Authors: Sabirov Davran , Ogurcov Sergei , Shulman Ilya , Kabdesh Ilyas , Garanina Ekaterina , Sufianov Albert , Rizvanov Albert , Mukhamedshina Yana 
Published: August 2023

AbstractBackgroundCytokines are actively involved in the regulation of the inflammatory and immune responses and play crucial importance for the outcome of spinal cord injury (SCI). Considering the importance of examining more objective and representative indicators of the patient’s condition is still required to reveal the fundamental patterns of abovementioned posttraumatic processes, including identification of changes in the expression of cytokines.MethodsWe performed a dynamic (3, 7 and 14 dpi) extended multiplex analysis of cytokine profiles in both CSF and blood serum of SCI patients with baseline American Spinal Injury Association Impairment Scale grades of A.ResultsThe data obtained showed a large elevation of IL-6 (>58 fold) in CSF and IFN-γ (>14 fold) in blood serum at 3 dpi with a downward trend as the post-traumatic period increases. The level of cytokine CCL26 was significantly elevated both CSF and blood serum at 3 days post-SCI while other cytokines did not show the same trend in the different biosamples.ConclusionsThe dynamic changes in cytokine levels observed in our study can explore the relationships with SCI region and injury severity, paving the way for a better understanding of the pathophysiology of SCI and potentially more targeted and personalized therapeutic interventions.
A retrospective longitudinal study of adenovirus group F, norovirus GI and GII, rotavirus, and enterovirus nucleic-acids in wastewater solids at two wastewater treatment plants: Solid-liquid partitioning and relation to clinical testing data
Authors: Boehm Alexandria B. , Hughes Bridgette , Duong Dorothea , Banaei Niaz , White Bradley J. , Wolfe Marlene K. 
Published: August 2023

AbstractBackgroundEnteric infections are important causes of morbidity and mortality, yet clinical surveillance is limited. Wastewater-based epidemiology (WBE) has been used to study community circulation of individual enteric viruses and panels of respiratory diseases, but there is limited work studying concurrent circulation of a suite of important enteric viruses.MethodsA retrospective WBE study was carried out at two wastewater treatment plants located in California, United States. Using droplet digital polymerase chain reaction (PCR), we measured concentrations of human adenovirus group F, enteroviruses, norovirus genogroups I and II, and rotavirus nucleic-acids in wastewater solids two times per week for 26 months (n=459 samples) between 2/1/21 and 4/14/23. A novel probe-based PCR assay was developed and validated for adenovirus. We compared viral nucleic-acid concentrations to positivity rates for viral infections from clinical specimens submitted to a local clinical laboratory to assess concordance between the data sets.FindingsWe detected all viral targets in wastewater solids. At both wastewater treatment plants, human adenovirus group F and norovirus GII nucleic-acids were detected at the highest concentrations (median concentrations greater than 105cp/g), while rotavirus RNA was detected at the lowest concentrations (median on the order of 103cp/g). Rotavirus, adenovirus group F, and norovirus nucleic-acid concentrations were positivity associated with clinical specimen positivity rates. Concentrations of tested viral nucleic-acids exhibited complex associations with SARS-CoV-2 and other respiratory viral nucleic-acids in wastewater, suggesting divergent transmission patterns.InterpretationThis study provides evidence for the use of wastewater solids for the sensitive detection of enteric virus targets in WBE programs aimed to better understand the spread of enteric disease at a localized, community level without limitations associated with testing many individuals. Wastewater data can inform clinical, public health, and individual decision making aimed to reduce transmission of enteric disease.
High-resolution diploid 3D genome reconstruction using Pore-C data
Authors: Chen Ying , Lin Zhuo-Bin , Wang Shao-Kai , Wu Bo , Niu Long-Jian , Zhong Jia-Yong , Sun Yi-Meng , Bai Xin , Liu Luo-Ran , Xie Wei , Luo Ruibang , Hou Chunhui , Luo Feng , Xiao Chuan-Le 
Published: August 2023

AbstractIn diploid organisms, spatial variations between homologous chromosomes are essential to many biological phenomena. Currently, it is still challenging to efficiently reconstruct a high-quality diploid 3D human genome. Here, we introduce Dip3D, reconstructing the diploid 3D human genome using Pore-C data of one sample. Dip3D has solved multiple problems in genome-wide SNV calling and haplo-tagging caused by the high sequencing error rates in Pore-C type data. Dip3D capitalizes on the high-order chromosomal interaction characteristics, enabling robust haplotype imputation and intricate haplotype-specific 3D structure discovery. Dip3D outperforms previous methods in data utilization rate, contact matrix resolution, and completeness by one order of magnitude. Moreover, Dip3D allows capturing haplotype high-order interactions that are unseen in Hi-C type data. We demonstrated the identified haplotype substructures such as Topologically Associating Domains (TADs) in the constructed 3D human genome, and unraveled connections between genic haplotype-specific high-order interactions and imbalanced allelic expression.
A trade-off in controlling upstream and downstream noise in signaling networks
Authors: Kong Ka Kit , Luo Chunxiong , Liu Feng 
Published: August 2023

AbstractSignal transduction, underpinning the function of a variety of biological systems, is inevitably affected by fluctuations. It remains intriguing how the timescale of a signaling network relates to its capability of noise control, specifically, whether long timescale can average out fluctuation or accumulate fluctuation. Here, we consider two noise components of the signaling system: the upstream noise from the fluctuation of the input signal and the downstream noise from the stochastic fluctuations of the network. We discover a fundamental trade-off in controlling the upstream and downstream noise: a longer timescale of the signaling network can buffer upstream noise, while accumulate downstream noise. Moreover, we confirm that this trade-off relation exists in real biological signaling networks such as a fold-change detection circuit and the p53 activation signaling system.Author SummaryInformation transmission is vital in biological systems, such as decoding the information regarding nutrient levels during chemotaxis or morphogen concentrations in tissue development. While fluctuations arising from the stochastic nature of biological processes inevitably affect information transmission, noise control mechanisms have been studied for decades. However, it remains controversial what the role of the slow dynamics (long timescale) is in noise control. On the one hand, it has been reported to attenuate noise by averaging out fluctuations. On the other hand, it is also proposed to amplify noise by accumulating fluctuations. Here we dissect the noise in signaling systems into two components: upstream noise originating from signal fluctuation, and downstream noise from the network stochasticity. Our analysis reveals that upstream noise negatively correlates with timescale, while downstream noise exhibits a positive correlation, indicating a fundamental trade-off in controlling the two noise components. Moreover, we provide an intuitive illustration to understand this phenomenon using the concept of landscape representation. Mathematically, we analytically derive a trade-off relation that agrees well with simulations. Our results uncover a new property of noise in signaling processes, deepening our understanding of noise control and proposing a new perspective in designing signaling network.
Secondary contact, introgressive hybridization and genome stabilization in sticklebacks
Authors: Feng Xueyun , Merilä Juha , Löytynoja Ari 
Published: August 2023

AbstractAdvances in genomic studies have revealed that hybridization in nature is pervasive and raised questions about the dynamics of different genetic and evolutionary factors following the initial hybridization event. While recent research has proposed that the genomic outcomes of hybridization might be predictable to some extent, many uncertainties remain. With comprehensive whole-genome sequence data, we investigated the genetic introgression between two divergent lineages of nine-spined sticklebacks (Pungitius pungitius) in the Baltic Sea. We found that the intensity and direction of selection on the introgressed variation varied across different genomic elements: while functionally important regions had experienced reduced rates of introgression, promoter regions showed enrichment. Despite the general trend of negative selection, we identified specific genomic regions that were enriched for introgressed variants and within these regions, we detected footprints of selection, indicating adaptive introgression. We found the selection against the functional changes to be strongest in the vicinity of the secondary contact zone and weaken as a function of distance from the initial contact. Altogether, the results suggest that the stabilization of introgressed variation in the genomes is a complex, multi-stage process involving both negative and positive selection. In spite of the predominance of negative selection against introgressed variants, we also found evidence for adaptive introgression variants likely associated with adaptation to Baltic Sea environmental conditions.
Population dynamic population delineation in North American birds
Authors: Witting Lars 
Published: August 2023

AbstractAndrewartha and Birch (1954) envisioned that natural populations are surrounded by ecological barriers, yet statistical estimates of population structure are almost completely driven by genetic analyses void of ecological information. I develop an ecological clustering routine that delineates natural populations from the synchronisation and desynchronisation in the population dynamics of continuously distributed species. The method is applied to the North American Breeding Bird Survey (Sauer et al. 2017), where it identifies two to five populations per species for 160 species, and leaves the population differentiation unresolved for 139 species. This provides one of the first statistical methods for population dynamics delineated population structure.
Human-brown bear conflicts in Türkiye are driven by increased human presence around protected areas
Authors: Sıkdokur Ercan , Naderi Morteza , Çeltik Elif , Aytekin M. Çisel Kemahlı , Kusak Josip , Sağlam İsmail K. , Şekercioğlu Çağan H. 
Published: August 2023

AbstractHuman-wildlife conflict is increasing steadily worldwide and is rapidly becoming an important challenge for the success of conservation programs. Brown bears, which suffer from reduced habitat suitability and quality globally, frequently conflict with humans. These animals need large home ranges to fulfill their habitat requirements. When space and food are restricted, brown bears frequently shift towards human-dominated landscapes that offer reliable food sources. As a country where most of the landscape and habitats are human-dominated, human-brown bear conflict events (HBCs) are frequent in Türkiye. However, there has been no formal analysis of the nature and scope of these conflicts at the country level. Here, using HBC data from 2017 to 2022, we determined the spatial and temporal dynamics of HBC events and generated a risk probability map based on anthropogenic predictors and geographic profiling, to determine the factors driving HBC across Türkiye. HBC events did not show any annual or seasonal trends but varied considerably across biogeographic regions, with most conflicts occurring along the Black Sea coast and Eastern Anatolia. Sixty percent of all conflicts were due to bear foraging behavior in human settlements while twelve percent were the result of human activity in forests, with 57% of all conflict events resulting in direct injury to either humans or bears. We found that distance to villages, distance to protected areas, distance to farmland and human footprint to be the most important factors contributing to conflict risk. Consequently, 21% of the country was found to be under human-bear conflict risk, with 43% of the risks occurring within a 10 km radius from the centers of protected areas. Our analyses indicate that the high occurrence of HBCs is mainly the result of limited natural areas and resources available to brown bears and the increasing human encroachment in and around core bear habitats.
Differentiable simulation to develop molecular dynamics force fields for disordered proteins
Authors: Greener Joe G 
Published: August 2023

AbstractImplicit solvent force fields are computationally efficient but can be unsuitable for running molecular dynamics on disordered proteins. Here I improve the a99SB-dispforce field and the GBNeck2 implicit solvent model to better describe disordered proteins. Differentiable molecular simulations with 5 ns trajectories are used to jointly optimise 108 parameters to better match explicit solvent trajectories. Simulations with the improved force field better reproduce the radius of gyration and secondary structure content seen in experiments, whilst showing slightly degraded performance on folded proteins and protein complexes. The force field, called GB99dms, reproduces the results of a small molecule binding study and improves agreement to experiment for the aggregation of amyloid peptides. GB99dms, which can be used in OpenMM, is available athttps://github.com/greener-group/GB99dms. This work is the first to show that gradients can be obtained directly from nanosecond-length differentiable simulations of biomolecules and highlights the effectiveness of this approach to training whole force fields to match desired properties.
Modeling effects of variable preBötzinger Complex network topology and cellular properties on opioid-induced respiratory depression and recovery
Authors: Chou Grant M. , Bush Nicholas E. , Phillips Ryan S. , Baertsch Nathan A. , Harris Kameron Decker 
Published: August 2023

AbstractThe pre-Bötzinger complex (preBotC), located in the medulla, is the essential rhythm-generating neural network for breathing. The actions of opioids on this network impair its ability to generate robust, rhythmic output, contributing to life-threatening opioid-induced respiratory depression (OIRD). The occurrence of OIRD varies across individuals and internal and external states, increasing the risk of opioid use, yet the mechanisms of this variability are largely unknown. In this study, we utilize a computational model of the preBötC to perform severalin silicoexperiments exploring how differences in network topology and the intrinsic properties of preBötC neurons influence the sensitivity of the network rhythm to opioids. We find that rhythms produced by preBötC networksin silicoexhibit variable responses to simulated opioids, similar to the preBötC networkin vitro. This variability is primarily due to random differences in network topology and can be manipulated by imposed changes in network connectivity and intrinsic neuronal properties. Our results identify features of the preBötC network that may regulate its susceptibility to opioids.Significance StatementThe neural network in the brainstem that generates the breathing rhythm is disrupted by opioid drugs. However, this response can be surprisingly unpredictable. By constructing computational models of this rhythm-generating network, we illustrate how random differences in the distribution of biophysical properties and connectivity patterns within individual networks can predict their response to opioids, and we show how modulation of these network features can make breathing more susceptible or resistant to the effects of opioids.