bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decomprolute: A benchmarking platform designed for multiomics-based tumor deconvolution
Authors: Feng Song , Calinawan Anna , Pugliese Pietro , Wang Pei , Ceccarelli Michele , Petralia Francesca , Gosline Sara JC 
Published: January 2023

Tumor deconvolution is a reliable way to disentangle the diverse cell types that comprise solid tumors. To date, however, both the algorithms developed to deconvolve tumor samples, and the gold standard datasets used to assess the algorithms are geared toward the analysis of gene expression (e.g., RNA-seq) rather than protein levels in tumor cells. While gene expression is less expensive to measure, protein levels provide a more accurate view of immune markers. To facilitate the development as well as improve the reproducibility and reusability of multi-omic deconvolution algorithms, we introduce Decomprolute, a Common Workflow Language framework that leverages containerization to compare tumor deconvolution algorithms across multiomic data sets. Decomprolute incorporates the large-scale multiomic data sets produced by the Clinical Proteomic Tumor Analysis Consortium (CPTAC), which include matched mRNA expression and proteomic data from thousands of tumors across multiple cancer types to build a fully open-source, containerized proteogenomic tumor deconvolution benchmarking platform. The platform consists of modular architecture and it comes with well-defined input and output formats at each module. As a result, it is robust and extendable easily with additional algorithms or analyses. The platform is available for access and use athttp://pnnl-compbio.github.io/decomprolute.MotivationTo provide a comprehensive platform for algorithm developers and researchers to benchmark and run tumor deconvolution algorithms on multiomic data.
Durotaxis bridges phase transition as a function of tissue stiffnessin vivo
Authors: Zhu Min , Gu Bin , Thomas Evan , Tao Hirotaka , Yung Theodora M. , Zhang Kaiwen , Rossant Janet , Sun Yu , Hopyan Sevan 
Published: January 2023

ABSTRACTPhysical processes ultimately drive morphogenetic cell movements. Two proposals are that 1) cells migrate toward stiffer tissue (durotaxis) and that 2) the extent of cell rearrangements reflects liquid-solid tissue phase. It is unclear whether and how these concepts are related. Here, we identify fibronectin-dependent tissue stiffness as a control variable that underlies and unifies these phenomenain vivo. In murine limb bud mesoderm, cells are either caged, move directionally by durotaxis or intercalate as a function of their location along a stiffness gradient. A unifying stiffness-phase transition model that is based on a Landau equation accurately predicts cell diffusivity upon loss or gain of fibronectin. Fibronectin is regulated by a WNT5A-YAP positive feedback pathway that controls cell movements, tissue shape and skeletal pattern. The results identify a key determinant of phase transition and show how durotaxis emerges in a mixed phase environmentin vivo.
High-yield, ligation-free assembly of DNA constructs with nucleosome positioning sequence repeats for single molecule manipulation assays
Authors: Lin Yi-Yun , Brouns Tine , Kolbeck Pauline J. , Vanderlinden Willem , Lipfert Jan 
Published: January 2023

ABSTRACTForce and torque spectroscopy have provided unprecedented insights into the mechanical properties, conformational transitions, and dynamics of DNA and DNA-protein complexes, notably nucleosomes. Reliable single-molecule manipulation measurements require, however, specific and stable attachment chemistries to tether the molecules of interest. Here, we present a functionalization strategy for DNA that enables high-yield production of constructs for torsionally constrained and very stable attachment. The method is based on two subsequent PCR reactions: first ∼380 bp long DNA strands are generated that contain multiple labels, which are used as “megaprimers” in a second PCR reaction to generate ∼kbp long double-stranded DNA constructs with multiple labels at the respective ends. We use DBCO-based click chemistry for covalent attachment to the surface and biotin-streptavidin coupling to the bead. The resulting tethers are torsionally constrained and extremely stable under force, with an average lifetime of 60 ± 3 hours at 45 pN. The high yield of the approach enables nucleosome reconstitution by salt dialysis on the functionalized DNA and we demonstrate proof-of-concept measurements on nucleosome assembly statistics and inner turn unwrapping under force. We anticipate that our approach will facilitate a range of studies of DNA interactions and nucleoprotein complexes under forces and torques.
Heterogeneous pseudobulk simulation enables realistic benchmarking of cell-type deconvolution methods
Authors: Hu Mengying , Chikina Maria 
Published: January 2023

AbstractComputational cell type deconvolution enables estimation of cell type abundance from bulk tissues and is important for understanding cell-cell interactions, especially in tumor tissues. With rapid development of deconvolution methods, many benchmarking studies have been published aiming for a comprehensive evaluation for these methods. Benchmarking studies rely on cell-type resolved single-cell RNA-seq data to create simulated pseudbulk datasets by adding individual cells-types in controlled proportions. In our work we show that the standard application of this approach, which uses randomly selected single cells, regardless of the intrinsic difference between them, generates synthetic bulk expression values that lack appropriate biological variance. We demonstrate why and how the current bulk simulation pipeline with random cells is unrealistic and propose a heterogeneous simulation strategy as a solution. Our heterogeneously simulated samples show realistic variance across hallmark gene-sets when comparing with real bulk samples from the TCGA dataset of the same tumor type. Using this new simulation pipeline to benchmark deconvolution methods we show that introducing biological heterogeneity has a notable effect on the results. Evaluating the robustness of different deconvolution approaches to heterogeneous simulation we find that reference-free methods that rely on simplex estimation perform poorly, marker-based methods and BayesPrism are most robust, while regress-based approaches fall in between. Importantly, we find that under the heterogeneous scenario marker based methods and BayesPrism outperform state of the art reference methods. Our findings highlight how different conceptual approaches can negate unmodeled heterogeneity and suggest that there is room for further methodological development.
A Transcriptional Cofactor Regulatory Network for theC. elegansIntestine
Authors: Horowitz Brent B. , Nanda Shivani , Walhout Albertha J.M. 
Published: January 2023

ABSTRACTChromatin modifiers and transcriptional cofactors (collectively referred to as CFs) work with DNA-binding transcription factors (TFs) to regulate gene expression. In multicellular eukaryotes, distinct tissues each execute their own gene expression program for accurate differentiation and subsequent functionality. While the function of TFs in differential gene expression has been studied in detail in many systems, the contribution of CFs has remained less explored. Here we uncovered the contributions of CFs to gene regulation in theCaenorhabditis elegansintestine. We first annotated 366 CFs encoded by theC. elegansgenome and assembled a library of 335 RNAi clones. Using this library, we analyzed the effects of individually depleting these CFs on the expression of 19 fluorescent transcriptional reporters in the intestine and identified 216 regulatory interactions. We found that different CFs interact specifically with different promoters, and that both essential and intestinally expressed CFs exhibit the highest proportion of interactions. We did not find all members of CF complexes acting on the same set of reporters but instead found diversity in the promoter targets of each complex component. Finally, we found that previously identified activation mechanisms for theacdh-1promoter use different CFs and TFs. Overall, we demonstrate that CFs function specifically rather than ubiquitously at intestinal promoters and provide an RNAi resource for reverse genetic screens.
Whole Genomes Reveal Evolutionary Relationships and Mechanisms Underlying Gene-Tree Discordance inNeodiprionSawflies
Authors: Herrig Danielle K. , Vertacnik Kim L. , Ridenbaugh Ryan D. , Everson Kathryn M. , Sim Sheina B. , Geib Scott M. , Weisrock David W. , Linnen Catherine R. 
Published: January 2023

AbstractRapidly evolving taxa are excellent models for understanding the mechanisms that give rise to biodiversity. However, developing an accurate historical framework for comparative analysis of such lineages remains a challenge due to ubiquitous incomplete lineage sorting and introgression. Here, we use a whole-genome alignment, multiple locus-sampling strategies, and locus-based and SNP-based species-tree methods to infer a species tree for eastern North AmericanNeodiprionspecies, a clade of pine-feeding sawflies (Order: Hymenopteran; Family: Diprionidae). We recovered a well-supported species tree that—except for three uncertain relationships—is robust to different strategies for analyzing whole-genome data. Despite this consistency, underlying gene-tree discordance is high. To understand this discordance, we use multiple regression to model topological discordance as a function of several genomic features. We find that gene-tree discordance tends to be higher in regions of the genome that may be more prone to gene-tree estimation error, as indicated by a lower density of parsimony-informative sites, a higher density of genes, a higher average pairwise genetic distance, and gene trees with lower average bootstrap support. Also, contrary to the expectation that discordance via incomplete lineage sorting is reduced in low-recombination regions of the genome, we find anegativecorrelation between recombination rate and topological discordance. We offer potential explanations for this pattern and hypothesize that it may be unique to lineages that have diverged with gene flow. Our analysis also reveals an unexpected discordance hotspot on Chromosome 1, which contains several genes potentially involved in mitochondrial-nuclear interactions and produces a gene-tree that resembles a highly discordant mitochondrial tree. Based on these observations, we hypothesize that our genome-wide scan for topological discordance has identified a nuclear locus involved in a mito-nuclear incompatibility. Together, these results demonstrate how phylogenomic analysis coupled with high-quality, annotated genomes can generate novel hypotheses about the mechanisms that drive divergence and produce variable genealogical histories across genomes.
A parametric model for estimating the timing and intensity of animal migration
Authors: Thompson Peter R. , Harrington Peter D. , Mallory Conor D. , Lele Subhash R. , Bayne Erin M. , Derocher Andrew E. , Edwards Mark A. , Campbell Mitch , Lewis Mark A. 
Published: January 2023

AbstractAnimals of many different species, trophic levels, and life history strategies migrate, and the improvement of animal tracking technology allows ecologists to collect increasing amounts of detailed data on these movements. Understanding when animals migrate is important for managing their populations, but is still difficult despite modelling advancements. We designed a model that parametrically estimates the timing of migration from animal tracking data. Our model identifies the beginning and end of migratory movements as signaled by changes in step length and turning angle distributions. To this end, we can also use the model to estimate how an animal’s movement changes when it begins migrating. We tested our model on three datasets: migratory ferruginous hawks (Buteo regalis) in the Great Plains and barren-ground caribou (Rangifer tarandus groenlandicus) in northern Canada, and non-migratory brown bears (Ursus arctos) from the Canadian Arctic. We estimated the beginning and end of migration in caribou and hawks to the nearest day, while confirming a lack of migratory behaviour in the brown bear population. The flexibility of our modelling framework allowed us to assess intricacies associated with each dataset: long-term stopover behaviour in ferruginous hawks anda prioriknowledge of caribou calving areas and behaviour. In addition to estimating when caribou and ferruginous hawks migrated, our model also identified differences in how the two populations migrated; ferruginous hawks achieved efficient migrations by increasing their movement rates while caribou migration was achieved through significant increases in directional persistence. Our approach is broadly applicable to many animal movement studies. We anticipate that rigorous assessment of migration metrics will aid understanding of both how and why animals move.
Ongoing amphibian trade into the United States threatens salamander biodiversity
Authors: Connelly Patrick J. , Ross Noam , Stringham Oliver C. , Eskew Evan A. 
Published: January 2023

ABSTRACTThe fungal pathogenBatrachochytrium salamandrivorans(Bsal) is a major potential threat to salamander biodiversity in North America, where it is not yet known to occur. In the United States, a 2016 policy restricted the trade in 20 salamander genera in attempts to preventBsalintroduction. However, little comprehensive data is available to evaluate the impact of this policy action. Here, we collated a dataset of United States amphibian imports from 1999 to 2021 and show that reported legal trade in the targeted taxa was effectively reduced by the ban. Unfortunately, amphibian trade into the United States continues to riskBsalintroduction given that other species and genera now known to carryBsalare still traded in large quantities (millions of live individuals annually). Additional policy responses focused onBsalcarrier taxa, especially frogs in the genusRana, could help mitigate the impact ofBsalon North American salamanders.
Somatic mutation but not aneuploidy differentiates lung cancer in never-smokers and smokers
Authors: Moorthi Sitapriya , Paguirigan Amy , Ko Minjeong , Pettinger Mary , Hoge Anna C. H. , Nag Anwesha , Patel Neil A. , Wu Feinan , Sather Cassie , Fitzgibbon Matthew P. , Thorner Aaron R. , Anderson Garnet L. , Ha Gavin , Berger Alice H. 
Published: January 2023

SummaryLung cancer in never-smokers disproportionately affects older women. To understand the mutational landscape of this cohort, we performed detailed genome characterization of 73 lung adenocarcinomas from participants of the Women’s Health Initiative (WHI). We find enrichment ofEGFRmutations in never-/light-smokers andKRASmutations in heavy smokers as expected, but we also show that the specific variants of these genes differ by smoking status, with important therapeutic implications. Mutational signature analysis revealed signatures of clock, APOBEC, and DNA repair deficiency in never-/light-smokers; however, the mutational load of these signatures did not differ significantly from those found in smokers. Last, tumors from both smokers and never-/light-smokers shared copy number subtypes, with no significant differences in aneuploidy. Thus, the genomic landscape of lung cancer in never-/light-smokers and smokers is predominantly differentiated by somatic mutations and not copy number alterations.
Joint effects of social interactions and environmental challenges on physiology, internal microbiome, and reproductive performance in tree swallows (Tachycineta bicolor)
Authors: Taff Conor C. , McNew Sabrina M. , Zimmer Cedric , Uehling Jennifer J. , Houtz Jennifer L. , Ryan Thomas A. , van Oordt David Chang , Injaian Allison S. , Vitousek Maren N. 
Published: January 2023

ABSTRACTThe social environment that individuals experience appears to be a particularly salient mediator of stress resilience, as the nature and valence of social interactions are often related to subsequent health, physiology, microbiota, and overall stress resilience. Relatively few studies have simultaneously manipulated the social environment and ecological challenges under natural conditions. Here, we report the results of experiments in wild tree swallows (Tachycineta bicolor) in which we manipulated both ecological challenges (predator encounters and flight efficiency reduction) and social interactions (by experimental dulling of a social signal). In two experiments conducted in separate years, we reversed the order of these treatments so that females experienced either an altered social environment followed by a challenge or vice-versa. Before, during, and after treatments were applied, we tracked breeding success, morphology and physiology (mass, corticosterone, and glucose), social interactions via an RFID sensor network, cloacal microbiome diversity, and fledging success. Overall, we found that predator exposure during the nestling period reduced the likelihood of fledging and that signal manipulation sometimes altered social interactions, but little evidence that the two categories of treatment interacted with each other. We discuss the implications of our results for understanding what types of challenges and what conditions are most likely to result in interactions between the social environment and ecological challenges.
Leafhopper transmits soybean stay-green associated virus to legume plants
Authors: Yin Jinlong , Hu Zhuangzhuang , Xu Shuqi , Hong Xin , Qiu Yanglin , Cheng Xinge , Wang Liqun , Shen Weiliang , Zhi Haijian , Li Kai , Xu Kai 
Published: January 2023

ABSTRACTA novel geminivirus, soybean stay-green associated virus (SoSGV), was previously shown to cause soybean delayed senescence and is associated with the incidences of soybean stay-green syndrome. The transmission methods of SoSGV were not yet understood. We captured insects belonging to 24 distinct species in a soybean field with the SoSGV outbreak and detected the presence of SoSGV only in leafhoppers and bean bugs (Riptortus pedestris). Caged feeding experiments using captured leafhoppers and bean bugs from soybean fields showed that leafhoppers, but not bean bugs, are vectors transmitting SoSGV. The common brown leafhopper (Orosius orientalis) is identified as the dominant leafhopper species and can establish colonies feeding on soybean plants in experimental conditions. An investigation of SoSGV defective DNA revealed that soybean genomic DNA could be inserted into the SoSGV genome, while sequences from wild soybean, red bean, and cowpea were also identified. We further showed that the common brown leafhopper could transmit SoSGV to wild soybean and red bean plants, emphasizing the vector role of the leafhopper in the transmission of SoSGV in the field.
When Geometric Deep Learning Meets Pretrained Protein Language Models
Authors: Wu Fang , Tao Yu , Radev Dragomir , Xu Jinbo 
Published: January 2023

AbstractGeometric deep learning has recently achieved great success in non-Euclidean domains, and learning on 3D structures of large biomolecules is emerging as a distinct research area. However, its efficacy is largely constrained due to the limited quantity of structural data. Meanwhile, protein language models trained on substantial 1D sequences have shown burgeoning capabilities with scale in a broad range of applications. Nevertheless, no preceding studies consider combining these different protein modalities to promote the representation power of geometric neural networks. To address this gap, we make the foremost step to integrate the knowledge learned by well-trained protein language models into several state-of-the-art geometric networks. Experiments are evaluated on a variety of protein representation learning benchmarks, including protein-protein interface prediction, model quality assessment, protein-protein rigid-body docking, and binding affinity prediction, leading to an overall improvement of 20% over baselines and the new state-of-the-art performance. Strong evidence indicates that the incorporation of protein language models’ knowledge enhances geometric networks’ capacity by a significant margin and can be generalized to complex tasks.
Evaluation Of Effect Of Bacteria On The Surface Of The Dental Implant
Authors: George S. Ajrish , Muralidharan N.P. , S Sahana , N Thiyaneswaran , R Subhashree 
Published: January 2023

ABSTRACTBackgroundDental Implantology is the most preferred treatment among patients who are opting for the replacement of their missing teeth. It is said that the success of the dental depends on the effectiveness of the dental implant bonding to the maxilla/mandible. This effectiveness depends on many factors. The microbial flora surrounding the dental implant also affects the integrity of the dental implant.AimThe study aims to analyze any effect bacteria on the surface of the implant.Materials and methodsIn the present study, 10 sterile dental implants were taken. Plaque samples were collected from patients with poor oral hygiene, who underwent dental implants and were under review for more than one month to six months. It was incubated with broth at 37 degrees Celcius. The surface changes in the dental implant were then observed in a scanning electron microscope.ResultsThe SEM results show a significant difference in the surface texture of the implant. There were pits, small craters, and cracks on the surface. The sharpness of the screw thread had also been noticeably blunt.ConclusionThus the study concludes that bacteria have a significant effect on the surface of the dental implant.
Zika virus infection induces IL-1β-mediated inflammatory responses by macrophages in the brain of an adult mouse model
Authors: Jeong Gi Uk , Lee Sumin , Kim Do Yeon , Lyu Jaemyun , Yun Gun Young , Ko Junsu , Kwon Young-Chan 
Published: January 2023

AbstractDuring the 2015/16 Zika virus (ZIKV) epidemic, ZIKV associated neurological diseases were reported in adults, including microcephaly, Guillain-Barre syndrome, myelitis, meningoencephalitis, and fatal encephalitis. However, the mechanisms underlying the neuropathogenesis of ZIKV infection are not yet fully understood. In this study, we used an adult ZIKV-infection mouse model (Ifnar1−/−) to investigate the mechanisms underlying neuroinflammation and neuropathogenesis. ZIKV infection induced the expression of proinflammatory cytokines, including IL-1β, IL-6, IFN-γ, and TNF-α, in the brains ofIfnar1−/−mice. RNA-seq analysis of the infected mouse brain also revealed that genes involved in innate immune responses and cytokine-mediated signaling pathways were significantly upregulated at 6 days post infection. Furthermore, ZIKV infection induced macrophage infiltration and activation, and augmented IL-1β expression, whereas microgliosis was not observed in the brain. Using human monocyte THP-1 cells, we confirmed that ZIKV infection promotes inflammatory cell death and increases IL-1β secretion. In addition, the expression of complement component C3, which is associated with neurodegenerative diseases and known to be upregulated by proinflammatory cytokines, was induced by ZIKV infection through the IL-1β-mediated pathway. An increase in C5a produced by complement activation in the brains of ZIKV-infected mice was also confirmed. Taken together, our results suggest that ZIKV infection of the brain in this animal model augments IL-1β expression in infiltrating macrophages and elicits IL-1β-mediated inflammation, which can lead to the destructive consequences of neuroinflammation.ImportanceZika virus (ZIKV) associated neurological impairments are an important global health problem. Our results suggest that ZIKV infection of the mouse brain can induce IL-1β-mediated inflammation and complement activation, contributing to the development of neurological disorders. Thus, our findings reveal a mechanism by which ZIKV induces neuroinflammation in the mouse brain. Although we used adult type I IFN receptor IFNAR knockout (Ifnar1−/−) mice owing to the limited mouse model of ZIKV pathogenesis, our conclusion could contribute to understanding ZIKV associated neurological diseases to develop treatment strategies based on these findings for the patients with ZIKV infection.