bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Computational Approach in Identification of Putative Risk Genes in Parkinsons Disease
Authors: Dave Bhargav , Majumder Prasenjit , Sarkar Shamayeeta 
Published: October 2021

AbstractThis study focussed on identification of risk genes involved in PD through analysis of microarray data. The two methods were applied viz; WGCNA and DEGs Analysis to identify important genes that are downregulated or upregulated in PD. Both methods show high agreement with each other and also with the available biomedical literature available on this neurodegenerative disease. On the basis of their p–value, 20 significantly upregulated and 19 significantly downregulated genes were found to be playing role in the manifestation of motor and non motor symptoms of the disease, as interpreted from the enrichment analysis.Gene expression dataset of Parkinson’s Disease (PD) used in this study was obtained from the GeneExpression Omnibus namely GSE8397, GSE20164, and GSE20295 (Edgar, 2002). Among the important genes extracted, the top downregulated and upregulated genes were studied using enrichment analysis. Out of the 19 common downregulated genes, 10 were directly associated with neuron development and differentiation. Two of the genes, FGF13 and CDC42 were associated with multiple signalling pathways. The gene NSF was found to be enriched with GABAergic synapse, associated with the predominating inhibitory neurotransmitter in the mammalian CNS. The inhibitory synapses are thought to provide a brake to neural firing.The upregulated genes DDIT4, HSPB1, NUPR1, GPNMB and CH13L1 were enriched with apoptotic signalling pathway while MT1M, MT1E, MT1F, MT1X were associated with mineral absorption pathways. Genes like CDC42 have already been reported to be potential diagnostic markers of PD in clinic (Chi et al., 2018).
Extreme COVID-19 waves reveal hyperexponential growth and finite-time singularity
Authors: Pavithran Induja , Sujith R. I. 
Published: October 2021

AbstractCoronavirus disease 2019 (COVID-19) has rapidly spread throughout our planet, bringing human lives to a standstill. Understanding the early transmission dynamics helps plan intervention strategies such as lockdowns that mitigate further spread, minimizing the adverse impact on humanity and the economy1–3. Exponential growth of infections was thought to be the defining feature of an epidemic in its initial growth phase4–7; any variation from an exponential growth was described by adjusting the parameters of the exponential model7,8. Here, we show that, contrary to common belief, early stages of extreme COVID-19 waves display an unbounded growth and finite-time singularity accompanying a hyperexponential power-law. The faster than exponential growth phase is hazardous and would entail stricter regulations. Such a power-law description allows us to characterize COVID-19 waves with single power-law exponents, better than piece-wise exponentials. Furthermore, we identify the presence of log-periodic patterns decorating the power-law growth. These log-periodic oscillations may enable better prediction of the finite-time singularity. We anticipate that our findings of hyperexponential growth and log-periodicity will help model the COVID-19 transmission more accurately.
SARS-COV-2 C.1.2 variant is highly mutated but may possess reduced affinity for ACE2 receptor
Authors: Yang Xiang-Jiao 
Published: October 2021

SUMMARYSARS-COV-2 evolution generates different variants and drives the pandemic. As the current main driver, delta variant bears little resemblance to the other three variants of concern (alpha, beta and gamma), raising the question what features the future variants of concern may possess. To address this important question, I searched through the GISAID database for potential clues. While investigating how beta variant has been evolving in South Africa, I noticed a small group of genomes mainly classified as C.1.2 variant, with one-year old boy identified in March 2021 being the index case. Over 80% patients are younger than 60. At the average, there are 46-47 mutations per genome, making this variant one of the most mutated lineages identified. A signature substitution is spike Y449H. Like beta and gamma variants, C.1.2 possesses E484K and N501Y. The genomes are heterogenous and encode different subvariants. Like alpha variant, one such subvariant encodes the spike substitution P681H at the furin cleavage site. In a related genome, this substitution is replaced by P681R, which is present in delta variant. In addition, similar to this variant of concern, three C.1.2 subvariants also encode T478K. Mechanistically, spike Y449 recognizes two key residues of the cell-entry receptor ACE2 and Y449H is known to impair the binding to ACE2 receptor, so C.1.2 variant may show reduced affinity for this receptor. If so, this variant needs other mutations to compensate for such deficiency. These results raise the question whether C.1.2 variant is as virulent as suggested by its unexpected high number of mutations.
Leveraging interindividual variability of regulatory activity refines genetic regulation of gene expression in schizophrenia
Authors: Alver Maris , Lykoskoufis Nikolaos , Ramisch Anna , Ongen Halit , Dermitzakis Emmanouil T. 
Published: October 2021

ABSTRACTSchizophrenia is a polygenic psychiatric disorder with limited understanding about the mechanistic changes in gene expression regulation. To elucidate on this, we integrate interindividual variability of regulatory activity with gene expression and genotype data captured from the prefrontal cortex of 272 cases and controls. We show that regulatory element activity is structured into 10,936 and 10,376 cis-regulatory domains in cases and controls, respectively, which display distinct regulatory element coordination structures in both states. By studying the interplay among genetic variants, gene expression and cis-regulatory domains, we ascertain that changes in coordinated regulatory activity tag alterations in gene expression levels (p=8.62e-06, OR=1.60), unveil case-specific QTL effects, and identify regulatory machinery changes for genes affecting synaptic function and dendritic spine morphology in schizophrenia. Altogether, we show that accounting for coordinated regulatory activity provides a novel mechanistic approach to reduce the search space for unveiling genetically perturbed regulation of gene expression in schizophrenia.
Conflicts of interest and physicians’ attitudes towards hydroxychloroquine as a treatment against COVID-19 A replication and extension of Roussel & Raoult (2020)
Authors: Freget Louis , Mulot Matthieu , Rochoy Michael , Ruggeri Valentin , Schöpfer Céline , Cova Florian 
Published: October 2021

AbstractHydroxychloroquine (HCQ) and its use as a treatment against COVID-19 have been at the center of heated debates. Some claim that physicians’ hostility towards HCQ was partly orchestrated by rival pharmaceutical companies seeking to promote their own treatment. In favor of this hypothesis, Roussel and Raoult (2020) have presented the results of a study in which they find a perfect positive correlation (ρ = 1.00) between French physicians’ attitudes towards HCQ and their conflict of interest with Gilead Sciences - the company that has promoted Remdesivir (REM) as a treatment against COVID-19. However, Roussel and Raoult’s study suffers from serious methodological shortcomings, among which is the fact that the statistical methods they employed might tend to artificially inflate correlations. In this study, we use a similar method and sample, but correct for their study’s original shortcomings: we provide a detailed, pre-registered method for collecting and coding data, computer inter-rater agreement and use a wide array of appropriate statistical methods to achieve a more reliable estimate the association between conflicts of interest and physicians’ attitudes towards HCQ. We conclude that Roussel and Raoult’s conclusion was misguided and that financial conflicts of interest were not the main predictors of the attitudes of physicians when compared to other factors, such as academic affiliation. Moreover, compared to other pharmaceutical companies, there was no specific link between attitudes towards HCQ and conflicts of interest with Gilead Sciences.
BioThings SDK: a toolkit for building high-performance data APIs in biomedical research
Authors: Lelong Sebastien , Zhou Xinghua , Afrasiabi Cyrus , Qian Zhongchao , Cano Marco Alvarado , Tsueng Ginger , Xin Jiwen , Mullen Julia , Yao Yao , Avila Ricardo , Taylor Greg , Su Andrew I , Wu Chunlei 
Published: October 2021

AbstractSummaryTo meet the increased need of making biomedical resources more accessible and reusable, Web APIs or web services have become a common way to disseminate knowledge sources. The BioThings APIs are a collection of high-performance, scalable, annotation as a service APIs that automate the integration of biological annotations from disparate data sources. This collection of APIs currently includes MyGene.info, MyVariant.info, and MyChem.info for integrating annotations on genes, variants, and chemical compounds, respectively. These APIs are used by both individual researchers and application developers to simplify the process of annotation retrieval and identifier mapping. Here, we describe the BioThings Software Development Kit (SDK), a generalizable and reusable toolkit for integrating data from multiple disparate data sources and creating high-performance APIs. This toolkit allows users to easily create their own BioThings APIs for any data type of interest to them, as well as keep APIs up-to-date with their underlying data sources.Availability and implementationThe BioThings SDK is built in Python and released via PyPI (https://pypi.org/project/biothings/).Its source code is hosted at its github repository (https://github.com/biothings/biothings.api).
Novel genetic sex markers reveal unexpected lack of, and similar susceptibility to, sex reversal in free-living common toads in both natural and anthropogenic habitats
Authors: Nemesházi Edina , Sramkó Gábor , Laczkó Levente , Balogh Emese , Szatmári Lajos , Vili Nóra , Ujhegyi Nikolett , Üveges Bálint , Bókony Veronika 
Published: October 2021

AbstractAnthropogenic environmental changes are affecting biodiversity and microevolution worldwide. Ectothermic vertebrates are especially vulnerable, since their sexual development can be disrupted by environmental changes, which can cause sex reversal, a mismatch between genetic and phenotypic sex, potentially leading to sex-ratio distortion and population decline. Despite these implications, we have scarce empirical knowledge on the incidence of sex reversal in nature. Populations in anthropogenic environments may experience sex reversal more frequently, or alternatively, they may adapt to resist sex reversal. To test these alternative hypotheses, we developed PCR-based genetic sex markers for the common toad (Bufo bufo). We assessed the prevalence of sex reversal in wild populations living in natural, agricultural and urban habitats, and the susceptibility of the same populations to two ubiquitous estrogenic pollutants in a common-garden experiment. We found negligible sex-reversal frequency in free-living adults despite the presence of various endocrine-disrupting pollutants in their breeding ponds. Individuals from different habitat types showed similar susceptibility to sex reversal in the laboratory: all genetic males developed female phenotype when exposed to 1 µg/L 17α- ethinylestradiol (EE2) during larval development, whereas no sex reversal occurred in response to 1 ng/L EE2 and a glyphosate-based herbicide with 3 µg/L or 3 mg/L glyphosate. The latter results do not support that populations in anthropogenic habitats would have either increased propensity for or higher tolerance to chemically induced sex reversal. Thus, the surprisingly low sex-reversal frequency in wild toads compared to other ectothermic vertebrates studied before might indicate idiosyncratic, potentially species-specific resistance to sex reversal.
FindZX: an automated pipeline for detecting and visualising sex chromosomes using whole-genome sequencing data
Authors: Sigeman Hanna , Sinclair Bella , Hansson Bengt 
Published: October 2021

AbstractSex chromosomes have evolved numerous times, as revealed by recent genomic studies. However, large gaps in our knowledge of sex chromosome diversity across the tree of life remain. Filling these gaps, through the study of novel species, is crucial for improved understanding of why and how sex chromosomes evolve. Characterization of sex chromosomes in already well-studied organisms is also important to avoid misinterpretations of population genomic patterns caused by undetected sex chromosome variation. Here we present findZX, an automated Snakemake-based computational pipeline for detecting and visualizing sex chromosomes through differences in genome coverage and heterozygosity between males and females. FindZX is user-friendly and scalable to suit different computational platforms and works with any number of male and female samples. An option to perform a genome coordinate lift-over to a reference genome of another species allows users to inspect sex-linked regions over larger contiguous chromosome regions, while also providing important between-species synteny information. To demonstrate its effectiveness, we applied findZX to publicly available genomic data from species belonging to widely different taxonomic groups (mammals, birds, reptiles, fish, and insects), with sex chromosome systems of different ages, sizes, and levels of differentiation. We also demonstrate that the lift-over method is robust over large phylogenetic distances (>80 million years of evolution).
A method for independent estimation of false localisation rate for phosphoproteomics
Authors: Ramsbottom Kerry A , Prakash Ananth , Riverol Yasset Perez , Camacho Oscar Martin , Martin Maria , Vizcaíno Juan Antonio , Deutsch Eric W , Jones Andrew R 
Published: October 2021

AbstractPhosphoproteomics methods are commonly employed in labs to identify and quantify the sites of phosphorylation on proteins. In recent years, various software tools have been developed, incorporating scores or statistics related to whether a given phosphosite has been correctly identified, or to estimate the global false localisation rate (FLR) within a given data set for all sites reported. These scores have generally been calibrated using synthetic data sets, and their statistical reliability on real datasets is largely unknown. As a result, there is considerable problem in the field of reporting incorrectly localised phosphosites, due to inadequate statistical control.In this work, we develop the concept of using scoring and ranking modifications on a decoy amino acid, i.e. one that cannot be modified, to allow for independent estimation of global FLR. We test a variety of different amino acids to act as the decoy, on both synthetic and real data sets, demonstrating that the amino acid selection can make a substantial difference to the estimated global FLR. We conclude that while several different amino acids might be appropriate, the most reliable FLR results were achieved using alanine and leucine as decoys, although we have a preference for alanine due to the risk of potential confusion between leucine and isoleucine amino acids. We propose that the phosphoproteomics field should adopt the use of a decoy amino acid, so that there is better control of false reporting in the literature, and in public databases that re-distribute the data. Data are available via ProteomeXchange with identifier PXD028840.
GoMi - A new gold standard corpus for miRNA Named Entity Recognition to test dictionary, rule-based and machine-learning approaches
Authors: Frericks-Zipper Anika , Stepath Markus , Schork Karin , Marcus Katrin , Turewicz Michael , Eisenacher Martin 
Published: October 2021

AbstractBiomarkers have been the focus of research for more than 30 years [REF1]. Paone et al. were among the first scientists to use the term biomarker in the course of a comparative study dealing with breast carcinoma [REF2]. In recent years, in addition to proteins and genes, miRNA or micro RNAs, which play an essential role in gene expression, have gained increased interest as valuable biomarkers. As a result, more and more information on miRNA biomarkers can be extracted via text mining approaches from the increasing amount of scientific literature. In the late 1990s the recognition of specific terms in biomedical texts has become a focus of bioinformatic research to automatically extract knowledge out of the increasing number of publications. For this, amongst other methods, machine learning algorithms are applied. However, the recognition (classification) capability of terms by machine learning or rule based algorithms depends on their correct and reproducible training and development. In the case of machine learning-based algorithms the quality of the available training and test data is crucial. The algorithms have to be tested and trained with curated and trustable data sets, the so-called gold or silver standards. Gold standards are text corpora, which are annotated by expertes, whereby silver standards are curated automatically by other algorithms. Training and calibration of neural networks is based on such corpora. In the literature there are some silver standards with approx. 500,000 tokens [REF3]. Also there are already published gold standards for species, genes, proteins or diseases. However, there is no corpus that has been generated specifically for miRNA. To close this gap, we have generated GoMi, a novel and manually curated gold standard corpus for miRNA. GoMi can be directly used to train ML-methods to calibrate or test different algorithms based on the rule-based approach or dictionary-based approach. The GoMi gold standard corpus was created using publicly available PubMed abstracts.GoMi can be downloaded here: https://github.com/mpc-bioinformatics/mirnaGS---GoMi.
Trivial Excitation Energy Transfer to Carotenoids is an Unlikely Mechanism for Non-Photochemical Quenching in LHCII
Authors: Gray Callum , Wei Tiejun , Polívka Tomáš , Daskalakis Vangelis , Duffy Christopher D. P. 
Published: October 2021

AbstractHigher plants defend themselves from bursts of intense light via the mechanism of Non-Photochemical Quenching (NPQ). It involves the Photosystem II (PSII) antenna protein (LHCII) adopting a conformation that favours excitation quenching. In recent years several structural models have suggested that quenching proceeds via energy transfer to the optically forbidden and short-lived S1 states of a carotenoid. It was proposed that this pathway was controlled by subtle changes in the relative orientation of a small number of pigments. However, quantum chemical calculations of S1 properties are not trivial and therefore its energy, oscillator strength and lifetime are treated as rather loose parameters. Moreover, the models were based either on a single LHCII crystal structure or Molecular Dynamics (MD trajectories) about a single minimum. Here we try and address these limitations by parameterizing the vibronic structure and relaxation dynamics of lutein in terms of observable quantities, namely linear absorption (LA) transient absorption (TA) and two-photon excitation (TPE) spectra. We also analyze a number of minima taken from an exhaustive meta-dynamical search of the LHCII potential energy surface. We show that trivial, Coulomb-mediated energy transfer to S1 is an unlikely quenching mechanism. Pigment movements are insufficient to switch the system between quenched and unquenched states. Modulation of S1 energy level as a quenching switch is similarly unlikely. Moreover, the quenching predicted by previous models is likely an artefact of quantum chemical over-estimation of S1 oscillator strength and the real mechanism likely involves non-trivial inter-molecular states.
Human placental bed transcriptomic profiling reveals inflammatory activation of endothelial cells in preeclampsia
Authors: Brouwers Laura , Wienke Judith , Mokry Michal , Nikkels Peter GJ , Vogelvang Tatjana E. , Franx Arie , van Wijk Femke , van Rijn Bas B. 
Published: October 2021

ABSTRACTRationaleFunctional characteristics of endothelial cells (ECs) within the human placental bed are unknown and may provide insight into the adaptive biology of ECs in disorders of vascular remodelling like preeclampsia.ObjectiveTo determine transcriptional profiles of human placental bed ECs and systemic biomarker profiles in women with normal pregnancy, and women with preeclampsia, a condition characterized by extensive EC dysfunction, poor development of spiral arteries underlying the placenta and long-term susceptibility to atherosclerosis and hypertension.Methods & resultsWe obtained biopsy samples from the uterine placental bed, of five women with preeclampsia with fetal growth restriction (FGR) due to impaired spiral artery development and four controls undergoing Caesarean section. CD31+CD146+ ECs were isolated and sorted by flow cytometry for RNA-sequencing using CEL-Seq2 protocol. Data were analyzed by unsupervised clustering, gene set enrichment (GSEA) and pathway analysis. 67 circulating biomarkers of EC function and inflammation were measured in 20 women with preeclampsia with FGR and 20 controls by multiplex immunoassay. Transcriptional profiling showed various differentially expressed genes (FDR<0.05) in placental bed ECs of preeclampsia patients, with enhanced activity of pathways associated with vasoconstriction, platelet activation and innate immunity. GSEA was suggestive of a VEGF- and PlGF deprived state of preeclampsia-derived ECs. Moreover, the transcriptomic profile was similar to that of human umbilical vein endothelial cells (HUVECs) treated with plasma from preeclampsia patients, pointing towards a central role for circulating factors in EC dysfunction. Unsupervised clustering of subjects by EC-related circulating factors identified distinct profiles for healthy pregnancy and preeclampsia, in particular for those women with low platelets and elevated liver enzymes, which was predominantly driven by sFLT-1, endoglin, PlGF, leptin, SAA-1 and sICAM-1.ConclusionsWe revealed inflammatory activation of EC and a key role for systemic factors in EC dysfunction in women with preeclampsia associated with impaired spiral artery development.