bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ingres: from single-cell RNA-seq data to single-cell probabilistic Boolean networks
Authors: Victori Pedro , Buffa Francesca M. 
Published: September 2022

AbstractMotivationThe current explosion of ’omics data has provided scientists with an unique opportunity to elucidate the inner workings of biological processes that remained opaque. For this, computational models are essential. Gene regulatory networks (GRN) have long been used as a way to integrate heterogeneous data into a discrete model, and are very useful to generate actionable hypotheses on the mechanisms governing these biological processes. Boolean networks are particularly popular for this kind of discrete models. When working with single-cell RNA-seq datasets a main focus of analysis is the differential expression between subpopulations of cells. Boolean networks are limited in this task, since they cannot easily represent different levels of expression, confined as they are to binary states. We set out to develop an algorithm that can fit Boolean networks with this kind of data, maintaining both the heterogeneity of the data and the simplicity and computational efficiency of these type of networks.ResultsHere we present Ingres (Inferring Probabilistic Boolean Networks of Gene Regulation Using Protein Activity Enrichment Scores) an open-source tool that uses single-cell sequencing data and prior knowledge GRNs to produce a probabilistic Boolean network (PBN) per each cell and/or cluster of cells in the dataset. Ingres allows to better capture the differences between cell phenotypes, using a continuous measure of protein activity while still confined to the simplicity of a GRN. We believe Ingres will be useful to better understand the heterogeneous makeup of cell populations, to gain insight into the specific circuits that drive certain phenotypes, and to use expression and other omics to infer computational cellular models in bulk or single-cell data.Availability and implementationIngres has been implemented as an R package, and it is publicly available at https://github.com/CBigOxf/ingres. It is currently being submitted to the public repository CRAN too. works seamlessly with existing software for single-cell RNA-seq analysis, and for network analysis, modelling and visualization.Contactpedro.victori@oncology.ox.ac.uk; francesca.buffa@unibocconi.it; francesca.buffa@imm.ox.ac.ukSupplementary informationSupplementary data are available online. Software documentation and an explanatory vignette are available on GitHub and as part of the R package.
Twenty-seven ZAD-ZNF genes of Drosophila melanogaster are orthologous to the embryo polarity determining mosquito gene cucoid
Authors: Li Muzi , Kasan Koray , Saha Zinnia , Yoon Yoseop , Schmidt-Ott Urs 
Published: September 2022

AbstractThe C2H2 zinc finger gene cucoid establishes anterior-posterior (AP) polarity in the early embryo of culicine mosquitoes. This gene is unrelated to genes that establish embryo polarity in other fly species (Diptera), such as the homeobox gene bicoid, which serves this function in the traditional model organism Drosophila melanogaster. The cucoid gene is a conserved single copy gene across lower dipterans but nothing is known about its function in other species, and its evolution in higher dipterans, including Drosophila, is unresolved. We found that cucoid is a member of the ZAD-containing C2H2 zinc finger (ZAD-ZNF) gene family and is orthologous to 27 of the 91 members of this family in D. melanogaster, including M1BP, ranshi, ouib, nom, zaf1, odj, Nnk, trem, Zif, and eighteen uncharacterized genes. Available knowledge of the functions of cucoid orthologs in Drosophila melanogaster suggest that the progenitor of this lineage specific expansion may played a role in regulating chromatin. We also describe many aspects of the gene duplication history of cucoid in the brachyceran lineage of D. melanogaster, thereby providing a framework for predicting potential redundancies among these genes in D. melanogaster.
The influence of genetic structure on phenotypic diversity in the Australian mango (Mangifera indica) gene pool
Authors: Wilkinson Melanie J. , Yamashita Risa , James Maddie E. , Bally Ian S.E. , Dillon Natalie L. , Ali Asjad , Hardner Craig M. , Ortiz-Barrientos Daniel 
Published: September 2022

AbstractGenomic selection is a promising breeding technique for tree crops to accelerate the development of new cultivars. However, factors such as genetic structure can create spurious associations between genotype and phenotype due to the shared history between populations with different trait values. Genetic structure can therefore reduce the accuracy of the genotype to phenotype map, a fundamental requirement of genomic selection models. Here, we employed 272 single nucleotide polymorphisms from 208 Mangifera indica cultivars to explore whether the genetic structure of the Australian mango gene pool explained variation in tree size, fruit blush colour and intensity. Our results show that genetic structure is weak, but cultivars imported from Southeast Asia (mainly those from Thailand) were genetically differentiated across multiple population genetic analyses. We find that genetic structure was strongly associated with phenotypic diversity in M. indica, suggesting that the history of these cultivars could drive spurious associations between loci and key mango phenotypes in the Australian mango gene pool. Incorporating such genetic structure in associations between genotype and phenotype has the potential to improve the accuracy of genomic selection, which can assist the development of new cultivars.
Distinct immune signatures discriminate SARS-CoV-2 vaccine combinations
Authors: Núñez Nicolás Gonzalo , Schmid Jonas , Power Laura , Alberti Chiara , Krishnarajah Sinduya , Kreutmair Stefanie , Unger Susanne , Blanco Sebastián , Konigheim Brenda , Marín Constanza , Onofrio Luisina , Kienzler Jenny Christine , Costa Pereira Sara da , Ingelfinger Florian ,   InmunoCovidCba,   InViV working group, Pasinovich Marina E. , Castelli Juan M , Vizzotti Carla , Schaefer Maximilian , Villar-Vesga Juan , Merten Carla Helena , Sethi Aakriti , Wertheimer Tobias , Lutz Mirjam , Vanoaica Danusia , Sotomayor Claudia , Gruppi Adriana , Münz Christian , Cardozo Diego , Barbás Gabriela , Lopez Laura , Carreño Paula , Castro Gonzalo , Raboy Elias , Gallego Sandra , Morón Gabriel , Cervi Laura , Acosta Rodriguez Eva V , Maletto Belkys A , Maccioni Mariana , Becher Burkhard 
Published: September 2022

AbstractSeveral vaccines have been found effective against COVID-19, usually administered in homologous regimens, with the same vaccine used for the prime and boost doses. However, recent studies have demonstrated improved protection via heterologous mix-and-match COVID-19 vaccine combinations, and a direct comparison among these regimens is needed to identify the best employment strategies. Here, we show a single-cohort comparison of changes to the humoral and cellular immune compartments following five different COVID-19 vaccines spanning three technologies (adenoviral, mRNA and inactivated vaccines). These vaccines were administered in a combinatorial fashion, resulting in sixteen different homologous and heterologous regimens. SARS-CoV-2-targeting antibody titres were highest when the boost dose consisted of mRNA-1273, independent of the vaccine used for priming. Priming with BBIBP-CorV induced less class-switching among spike-binding memory B cells and the highest antigen-specific T cell responses in heterologous combinations. These were generally more immunogenic in terms of specific antibodies and cellular responses compared to homologous regimens. Finally, single-cell analysis of 754 samples revealed specific B and T cell signatures of the vaccination regimens, indicating distinctive differences in the immune responses. These data provide new insights on the immunological effects of COVID-19 vaccine combinations and a framework for the design of improved vaccination strategies for other pathogens and cancer.
Persistent somatic symptoms are key to individual illness perception at one year after COVID-19
Authors: Hüfner Katharina , Tymoszuk Piotr , Sahanic Sabina , Luger Anna , Boehm Anna , Pizzini Alex , Schwabl Christoph , Koppelstätter Sabine , Kurz Katharina , Asshoff Malte , Mosheimer-Feistritzer Birgit , Pfeifer Bernhard , Rass Verena , Schroll Andrea , Iglseder Sarah , Egger Alexander , Wöll Ewald , Weiss Günter , Helbok Raimund , Widmann Gerlig , Sonnweber Thomas , Tancevski Ivan , Sperner-Unterweger Barbara , Löffler-Ragg Judith 
Published: September 2022

AbstractBackgroundSequelae of Coronavirus disease 2019 (COVID-19) were investigated by both patient-initiated and academic initiatives. Patient’s subjective illness perceptions might differ from physician’s clinical assessment results. Herein, we explored factors influencing patient’s perception during COVID-19 recovery.MethodsParticipants of the prospective observation CovILD study with persistent somatic symptoms or cardiopulmonary findings at the clinical follow-up one year after COVID-19 were analyzed (n = 74). Explanatory variables included baseline demographic and comorbidity data, COVID-19 course and one-year follow-up data of persistent somatic symptoms, physical performance, lung function testing (LFT), chest computed tomography (CT) and trans-thoracic echocardiography (TTE). Factors affecting illness perception (Brief Illness Perception Questionnaire, BIPQ) were identified by penalized multi-parameter regression and unsupervised clustering.ResultsIn modeling, 47% of overall illness perception variance at one year after COVID-19 was attributed to fatigue intensity, reduced physical performance, hair loss and baseline respiratory comorbidity. Overall illness perception was independent of LFT results, pulmonary lesions in CT or heart abnormality in TTE. As identified by clustering, persistent somatic symptom count, fatigue, diminished physical performance, dyspnea, hair loss and sleep problems at the one-year follow-up and severe acute COVID-19 were associated with the BIPQ domains of concern, emotional representation, complaints, disease timeline and consequences.ConclusionPersistent somatic symptoms rather than clinical assessment results, revealing lung and heart abnormalities, impact on severity and quality of illness perception at one year after COVID-19 and may foster unhelpful coping mechanisms. Besides COVID-19 severity, individual illness perception should be taken into account when allocating rehabilitation and psychological therapy resources.Study registrationClinicalTrials.gov: NCT04416100.
Differences in maternally inherited and age-related de novo mitochondrial DNA variants between ART and spontaneously conceived individuals associate with low birth weight
Authors: Mertens Joke , Belva Florence , van Montfoort Aafke P.A. , Zambelli Filippo , Seneca Sara , de Deckersberg Edouard Couvreu , Bonduelle Maryse , Tournaye Herman , Stouffs Katrien , Barbé Kurt , Smeets Hubert , Van de Velde Hilde , Sermon Karen , Blockeel Christophe , Spits Claudia 
Published: September 2022

ABSTRACTBackgroundChildren born using assisted reproductive technologies (ART) have an increased risk of a lower birth weight, the cause of which remains unclear. As a causative factor, we hypothesized that variants in the mitochondrial DNA (mtDNA) that are not associated with disease, may explain changes in birth weight.MethodsWe deep-sequenced the mtDNA of 451 ART and spontaneously conceived (SC) individuals, 157 mother-child pairs and 113 individual oocytes from either natural menstrual cycles or cycles with ovarian stimulation (OS). The mtDNA genotypes were compared across groups and logistic regression and discriminant analysis were used to study the impact of the different factors on birth weight percentile.ResultsART individuals more frequently carried variants with higher heteroplasmic loads in protein and rRNA-coding regions. These differences in the mitochondrial genome were also predictive of the risk of a lower birth weight percentile, irrespective of the mode of conception but with a sex-dependent culture medium effect. The higher incidence of these variants in ART individuals results both from maternal transmission and de novo mutagenesis, which we found not to be caused by OS but to be associated to maternal ageing.ConclusionsMtDNA variants in protein and rRNA coding regions are associated with a lower birth weight and are more frequently observed in ART children. We propose that these non-disease associated variants can result in a suboptimal mitochondrial function that impacts birth weight. Future research will establish the long-term health consequences of these changes and how these findings will impact the clinical practice and patient counselling in the future.
ChimeraTE: A pipeline to detect chimeric transcripts derived from genes and transposable elements
Authors: Oliveira Daniel S. , Fablet Marie , Larue Anaïs , Vallier Agnès , Carareto Claudia M. A. , Rebollo Rita , Vieira Cristina 
Published: September 2022

ABSTRACTTransposable elements (TEs) produce structural variants and are considered an important source of genetic diversity. Notably, TE-gene fusion transcripts,i.e.,chimeric transcripts, have been associated with adaptation in several species. However, the identification of these chimeras remains hindered due to the lack of detection tools at a transcriptome-wide scale, and to the reliance on a reference genome, even though different individuals/cells/strains have different TE insertions. Therefore, we developed ChimeraTE, a pipeline that uses paired-end RNA-seq reads to identify chimeric transcripts through two different modes. Mode 1 is the reference-guided approach that employs canonical genome alignment, and Mode 2 identifies chimeras derived from fixed or insertionally polymorphic TEs without any reference genome. We have validated both modes using RNA-seq data from fourDrosophila melanogasterwild-type strains. We found ∼1.12% of all genes generating chimeric transcripts, most of them from TE-exonized sequences. Approximately ∼23% of all detected chimeras were absent from the reference genome, indicating that TEs belonging to chimeric transcripts may be recent, polymorphic insertions. ChimeraTE is the first pipeline able to automatically uncover chimeric transcripts without a reference genome, consisting of two running Modes that can be used as a tool to investigate the contribution of TEs to transcriptome plasticity.
A unique case in whichKimoto-style fermentation was completed withLeuconostocas the dominant genus without transitioning toLactobacillus
Authors: Ito Kohei , Niwa Ryo , Yamagishi Yuta , Kobayashi Ken , Tsuchida Yuji , Hoshino Genki , Nakagawa Tomoyuki , Watanabe Takashi 
Published: September 2022

AbstractTheKimoto-style fermentation starter is a traditional preparation method ofsakebrewing. In this process, specific microbial transition patterns have been observed within nitrate-reducing bacteria and lactic acid bacteria during the production process of the fermentation starter. We have characterized phylogenetic compositions and diversity of the bacterial community in asakebrewery performing theKimoto-style fermentation. Comparing the time-series changes with othersakebreweries previously reported, we found a novel type ofKimoto-style fermentation in which the microbial transition differed significantly from other breweries during the fermentation step. Specifically, the lactic acid bacteria,Leuconostocspp. was a predominant species in the late stage in the preparation process of fermentation starter, on the other hand,Lactobacillusspp., which plays a pivotal role in other breweries, was not detected in this analysis. The discovery of this new variation of microbiome transition inKimoto-style fermentation has further deepened our understanding of the diversity ofsakebrewing.
Mapping of Glutamate Metabolism using 1H FID-MRSI after oral Administration of [1-13C]Glc at 9.4 T
Authors: Ziegs Theresia , Ruhm Loreen , Wright Andrew , Henning Anke 
Published: September 2022

AbstractGlutamate is the major excitatory transmitter in the brain and malfunction of the related metabolism is associated with various neurological diseases and disorders. The observation of labeling changes in the spectra after the administration of a13C labelled tracer is a common tool to gain better insights into the function of the metabolic system. But so far, only a very few studies presenting the labelling effects in more than two voxels to show the spatial dependence of metabolism.In the present work, the labeling effects were measured in a transversal plane in the human brain using ultra-short TE and TR 1H FID-MRSI. The measurement set-up was most simple: The [1-13C]Glc was administered orally instead of intravenous and the spectra were measured with a pure 1H technique without the need of a13C channel (as Boumezbeur et al. demonstrated in 2004). Thus, metabolic maps and enrichment curves could be obtained for more metabolites and in more voxels than ever before in human brain. Labeling changes could be observed in [4-13C]glutamate, [3-13C]glutamate+glutamine, [2-13C]glutamate+glutamine, [4-13C]glutamine, [2,3-13C]aspartate and [6-13C]N-acetyl aspartate with a high temporal (3.6 min) and spatial resolution (32×32 grid with nominal voxel size of 0.33 μL) in five volunteers.
In silicoidentification of miRNAs related to mitochondrial dysfunction in amyotrophic lateral sclerosis
Authors: Gulcin Baykal , Burcin Erkal , Senay Vural Korkut 
Published: September 2022

AbstractNon-coding, single-stranded RNA molecules known as microRNAs (miRNAs) regulate gene expression via mRNA degradation after transcription. As a result, they affect a number of pathways in organisms that are important for both health and disease. miRNAs can be utilized as potential diagnostic, prognostic, and therapeutic biomarkers for neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS). Neuronal cells are highly dependent on mitochondria, and mitochondrial dysfunction has been linked to neurodegenerative diseases. Pathological changes in ALS are associated with disruptions in mitochondrial structure, bioenergetics, and calcium homeostasis. In this study, we used anin silicoapproach to identify miRNAs associated with mitochondrial dysfunction in ALS based on target genes that are implied in both ALS and mitochondrial dysfunction. A literature search revealed the genes SOD1, FUS, TARDBP, C9orf72, CHCHD10, OPTN, VCP, TBK1 and BCL2 that cause mitochondrial dysfunction and are involved in the pathogenesis of ALS. Pathway enrichment analyses using Enrichr, g:Profiler, and CROssBAR tools confirmed that the identified genes have significant associations with ALS, mitochondrial dysfunction, and neuron differentiation. In silico miRNA predictions have been made using the databases miRWalk, miRTargetLink, TargetScan, and miRNet. A Venn diagram tool was used to select common miRNAs, and finally 28 miRNAs were discovered. One set of 28 miRNAs were subjected to set analysis using the miRNet and TAM tools for functional and enrichment analyses, respectively. In both databases, three common miRNAs, hsa-miR-9-5p, hsa-miR-141-3p and hsa-miR-125b, were found to be linked to ALS.
Nucleotide level linkage of transcriptional elongation and polyadenylation
Authors: Geisberg Joseph V. , Moqtaderi Zarmik , Fong Nova , Erickson Benjamin , Bentley David L. , Struhl Kevin 
Published: September 2022

ABSTRACTAlternative polyadenylation yields many mRNA isoforms whose 3’ termini occur disproportionately in clusters within 3’ UTRs. Previously, we showed that profiles of poly(A) site usage are regulated by the rate of transcriptional elongation by RNA polymerase (Pol) II (Geisberg et., 2020). Pol II derivatives with slow elongation rates confer an upstream-shifted poly(A) profile, whereas fast Pol II strains confer a downstream-shifted poly(A) profile. In yeast, upstream and downstream shifts within isoform clusters occur steadily at the nucleotide level. In contrast, changes from one isoform to the next are much smaller between clusters, even when the distances between them are relatively large. GC content in a region 13-30 nt downstream from isoform clusters is linked to Pol II elongation rate. In human cells, the upstream shift caused by a slow Pol II mutant also occurs continuously at the nucleotide level within clusters, but not between them. Pol II occupancy increases just downstream of the most speed-sensitive poly(A) sites, suggesting a linkage between reduced elongation rate and cluster formation. These observations suggest that 1) Pol II elongation speed affects the nucleotide-level dwell time allowing polyadenylation to occur, 2) poly(A) site clusters are linked to the local elongation rate and hence do not arise simply by intrinsically imprecise cleavage and polyadenylation of the RNA substrate, 3) DNA sequence elements can affect Pol II elongation and poly(A) profiles, and 4) the cleavage/polyadenylation and Pol II elongation complexes are spatially, and perhaps physically, coupled so that polyadenylation occurs rapidly upon emergence of the nascent RNA from the Pol II elongation complex.
Individual variation in the avian gut microbiota: the influence of host state and environmental heterogeneity
Authors: Somers Shane E. , Davidson Gabrielle L. , Johnson Crystal N. , Reichert Michael S. , Crane Jodie M. S. , Paul Ross R. , Stanton Catherine , Quinn John L. 
Published: September 2022

AbstractThe gut microbiome has important consequences for fitness, yet the complex, interactive nature of ecological factors that influence the gut microbiome has scarcely been investigated in natural populations. We sampled the gut microbiota of wild great tits (Parus major) at different life stages and across multiple conifer and mixed woodland fragments, allowing us to evaluate multiple factors that relate to within-individual gut microbiota acquisition, including habitat type, nest position and life history traits. The gut microbiota varied with both environment and life-history in ways that were largely dependent on age. Notably, it was the nestling, as opposed to the adult gut microbiota that was most sensitive to ecological variation, pointing to a high degree of developmental plasticity. Individual nestling differences in gut microbiota were consistently different (repeatable) from one to two weeks of life, driven entirely by the effect of sharing the same nest. Our findings point to important early developmental windows in which the gut microbiota are most sensitive to environmental variation and suggest reproductive timing, and hence parental quality or food availability, interact with the microbiome.
Identification of Biomarker Genes Based on Multi-Omics Analysis in Non-Small Cell Lung Cancer
Authors: Xia Ji , He Hai-bin , Liu Ying , Wang Yi , Shu Kun-Xian , Ma Ming-Yue 
Published: September 2022

AbstractBackgroundNon-small cell lung cancer (NSCLC) is a complex disease with a high mortality rate and a poor prognosis, but its molecular mechanisms and effective biomarkers are still unclear. Comprehensive analysis of multiple histological data can effectively exclude random events and is helpful in improving the reliability of the findings. In this study, we used three types of omics data, RNA-seq, microRNA-seq, and DNA methylation data, from public databases to explore the potential biomarker genes of two major subtypes of NSCLC.ResultsThrough the combined differential analysis of multi-omics, we found 873 and 1378 potential high-risk genes in LUAD and LUSC, respectively. Then, we used WGCNA and PPI analyses to identify hub-genes and LASSO regression to construct prognostic models, and we obtained 15 prognostic genes. We also used survival analysis, univariate COX analysis, and GEO datasets to validate prognostic genes. Finally, we found ten genes associated with NSCLC, and eight of them have been reported in previous research.ConclusionsIn this study, two novel biomarker genes were identified: NES and ESAM. The two genes were both gene expression down-regulation and DNA methylation up-regulation, and regulated by miR-122 and miR-154. Moreover, the NES gene can contribute to the clinical diagnosis and prognosis of NSCLC.