bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quality control of variant peptides identified through proteogenomics- catching the (un)usual suspects
Authors: Raj Anurag , Aggarwal Suruchi , Yadav Amit Kumar , Dash Debasis 
Published: June 2023

AbstractVariant peptides resulting from translation of single nucleotide polymorphisms (SNPs) can lead to aberrant or altered protein functions and thus hold translational potential for disease diagnosis, therapeutics and personalized medicine. Variant peptides detected by proteogenomics are fraught with high number of false positives. Class-specific FDR along with ad-hoc post-search filters have been employed to tackle this issue, but there is no uniform and comprehensive approach to assess variant quality. These protocols are mostly manual or tedious, and not accessible across labs. We present a software tool, PgxSAVy, for the quality control of variant peptides. PgxSAVy provides a rigorous framework for quality control and annotations of variant peptides on the basis of (i) variant quality, (ii) isobaric masses, and (iii) disease annotation. PgxSAVy was able to segregate true and false variants with 98.43% accuracy on simulated data. We then used ∼2.8 million spectra (PXD004010 and PXD001468) and identified 12,705 variant PSMs, of which PgxSAVy evaluated 3028 (23.8%), 1409 (11.1%) and 8268 (65.1%) as confident, semi-confident and doubtful respectively. PgxSAVy also annotates the variants based on their pathogenicity and provides support for assisted manual validation. In these datasets, it identified previously found variants as well some novel variants not seen in original studies. The confident variants identified the importance of mutations in glycolysis and gluconeogenesis pathways in Alzheimer’s disease. The analysis of proteins carrying variants can provide fine granularity in discovering important pathways. PgxSAVy will advance personalized medicine by providing a comprehensive framework for quality control and prioritization of proteogenomics variants.AvailabilityPgxSAVy is freely available athttps://github.com/anuragraj/PgxSAVyKey PointsVariant peptide in proteogenomics have high rates of false positivesclass-specific FDR is not sufficiently effective, and tedious manual filtering is not scalableWe developed PgxSAVy for automated quality control and disease annotation of variant peptides from proteogenomics search resultsPgxSAVy was validated using simulation data and manually annotated variant PSMsIndependent application on large datasets on Alzheimer’s and HEK cell lines demonstrated that PgxSAVy discovered known and novel mutations with important biological roles.Graphical Abstract
rCRUX: A Rapid and Versatile Tool for Generating Metabarcoding Reference libraries in R
Authors: Curd Emily E. , Gal Luna , Gallego Ramon , Nielsen Shaun , Gold Zachary 
Published: June 2023

AbstractKey to making accurate taxonomic assignments are curated, comprehensive reference barcode databases. However, the generation and curation of such databases has remained challenging given the large and continuously growing volumes of DNA sequence data and novel reference barcode targets. Monitoring and research applications require a greater diversity of specialized gene regions and targeted taxa to meet taxonomic classification goals then are currently curated by professional staff. Thus, there is a growing need for an easy to implement tool that can generate comprehensive metabarcoding reference libraries for any bespoke locus. We address this need by reimagining CRUX from the Anacapa Toolkit and present the rCRUX package in R. The typical workflow involves searching for plausible seed amplicons (get_seeds_local() orget_seeds_remote()) by simulatingin silicoPCR to acquire seed sequences containing a user-defined primer set. Next these seeds are used to iteratively blast search seed sequences against a local NCBI formatted database using a taxonomic rank based stratified random sampling approach (blast_seeds()) that results in a comprehensive set of sequence matches. This database is dereplicated and cleaned (derep_and_clean_db()) by identifying identical reference sequences and collapsing the taxonomic path to the lowest taxonomic agreement across all matching reads. This results in a curated, comprehensive database of primer specific reference barcode sequences from NCBI. We demonstrate that rCRUX provides more comprehensive reference databases for the MiFish Universal Teleost 12S, Taberlet trnl, and fungal ITS locus than CRABS, METACURATOR, RESCRIPt, and ECOPCR reference databases. We then further demonstrate the utility of rCRUX by generating 16 reference databases for metabarcoding loci that lack dedicated reference database curation efforts. The rCRUX package provides a simple to use tool for the generation of curated, comprehensive reference databases for user-defined loci, facilitating accurate and effective taxonomic classification of metabarcoding and DNA sequence efforts broadly.
A combined computational and experimental investigation of the filtration function of splenic macrophages in sickle cell disease
Authors: Li Guansheng , Qiang Yuhao , Li He , Li Xuejin , Buffet Pierre A. , Dao Ming , Karniadakis George Em 
Published: June 2023

AbstractBeing the largest lymphatic organ in the body, the spleen also constantly controls the quality of red blood cells (RBCs) in circulation through its two major filtration components, namely interendothelial slits (IES) and red pulp macrophages. In contrast to the extensive studies in understanding the filtration function of IES, there are relatively fewer works on investigating how the splenic macrophages retain the aged and diseased RBCs, i.e., RBCs in sickle cell disease (SCD). Herein, we perform a computational study informed by companion experiments to quantify the dynamics of RBCs captured and retained by the macrophages. We first calibrate the parameters in the computational model based on microfluidic experimental measurements for sickle RBCs under normoxia and hypoxia, as those parameters are not available in the literature. Next, we quantify the impact of a set of key factors that are expected to dictate the RBC retention by the macrophages in the spleen, namely, blood flow conditions, RBC aggregation, hematocrit, RBC morphology, and oxygen levels. Our simulation results show that hypoxic conditions could enhance the adhesion between the sickle RBCs and macrophages. This, in turn, increases the retention of RBCs by as much as five-fold, which could be a possible cause of RBC congestion in the spleen of patients with SCD. Our study on the impact of RBC aggregation illustrates a ‘clustering effect’, where multiple RBCs in one aggregate can make contact and adhere to the macrophages, leading to a higher retention rate than that resulting from RBC-macrophage pair interactions. Our simulations of sickle RBCs flowing past macrophages for a range of blood flow velocities indicate that the increased blood velocity could quickly attenuate the function of the red pulp macrophages on detaining aged or diseased RBCs, thereby providing a possible rationale for the slow blood flow in the open circulation of the spleen. Furthermore, we quantify the impact of RBC morphology on their tendency to be retained by the macrophages. We find that the sickle and granular-shaped RBCs are more likely to be filtered by macrophages in the spleen. This finding is consistent with the observation of low percentages of these two forms of sickle RBCs in the blood smear of SCD patients. Taken together, our experimental and simulation results aid in our quantitative understanding of the function of splenic macrophages in retaining the diseased RBCs and provide an opportunity to combine such knowledge with the current knowledge of the interaction between IES and traversing RBCs to apprehend the complete filtration function of the spleen in SCD.
Chronic intermittent hypoxia induced-dysmetabolism is associated with hepatic oxidative stress, mitochondrial dysfunction and inflammation
Authors: Fernandes Joana L. , Martins Fátima O. , Olea Elena , Prieto-Lloret Jesus , Braga Patrícia C. , Sequeira Catarina O. , Pereira Sofia A. , Alves Marco G. , Rocher Asunción , Conde Silvia V. 
Published: June 2023

AbstractThe association between obstructive sleep apnea (OSA) and metabolic disorders is well-established but the underlying mechanisms that elucidate this relationship remain incompletely understood. Since the liver is a major organ in the maintenance of metabolic homeostasis, we hypothesize that liver dysfunction plays a crucial role in the pathogenesis of metabolic dysfunction associated with obstructive sleep apnea (OSA). Herein, we explored the underlying mechanisms of this association within the liver. Experiments were performed in male Wistar rats fed with a control or high fat (HF) diet (60% lipid-rich) for 12 weeks. Half of the groups were exposed to chronic intermittent hypoxia (CIH) (30 hypoxic (5% O2) cycles, 8 h/day) that mimics OSA, in the last 15 days. Insulin sensitivity and glucose tolerance were assessed. Liver samples were collected for evaluation of lipid deposition, insulin signaling, glucose homeostasis, hypoxia, oxidative stress, antioxidant defenses, mitochondrial biogenesis and inflammation. Both CIH and HF diet induced dysmetabolism, a state not aggravated in animals submitted to HF plus CIH. CIH aggravates hepatic lipid deposition in obese animals. Hypoxia-inducible factors levels were altered by these stimuli. CIH decreased the levels of oxidative phosphorylation complexes in both groups and the levels of SOD-1. HF diet reduced mitochondrial density and hepatic antioxidant capacity. CIH and HF diet produced alterations in cysteine-related thiols and pro-inflammatory markers. The results obtained suggest that hepatic mitochondrial dysfunction and oxidative stress, leading to inflammation, may be significant factors contributing to the development of dysmetabolism associated with OSA.
Genome wide assessment of genetic diversity and transcript variations in 17 accessions of the model diatomPhaeodactylum tricornutum
Authors: Timothée Chaumier , Yang Feng , Manirakiza Eric , Ait-Mohamed Ouardia , Wu Yue , Chandola Udita , Jesus Bruno , Piganeau Gwenael , Groisillier Agnès , Tirichine Leila 
Published: June 2023

AbstractDiatoms, a prominent group of phytoplankton, have a significant impact on both the oceanic food chain and carbon sequestration, thereby playing a crucial role in regulating the climate. These highly diverse organisms show a wide geographic distribution across various latitudes. In addition to their ecological significance, diatoms represent a vital source of bioactive compounds that are widely used in biotechnology applications. In the present study, we investigated the genetic and transcriptomic diversity of 17 accessions of the model diatomPhaeodactylum tricornutumincluding those sampled a century ago as well as more recently collected accessions. The analysis of the data reveals a higher genetic diversity and the emergence of novel clades, indicating an increasing diversity within theP. tricornutumpopulation structure, compared to the previous study and a persistent long-term balancing selection of genes in old and newly sampled accessions. However, the study did not establish a clear link between the year of sampling and genetic diversity, thereby, rejecting the hypothesis of loss of heterozygoty in cultured strains. Transcript analysis identified novel transcript including non-coding RNA and other categories of small RNA such as PiwiRNAs. Additionally, transcripts analysis using differential expression as well as Weighted Gene Correlation Network Analysis has provided evidence that the suppression or downregulation of genes cannot be solely attributed to loss of function mutations. This implies that other contributing factors, such as epigenetic modifications, may play a crucial role in regulating gene expression. Our study provides novel genetic resources, which are now accessible through the platform PhaeoEpiview (https://PhaeoEpiView.univ-nantes.fr), that offer both ease of use and advanced tools to further investigate microalgae biology and ecology, consequently enriching our current understanding of these organisms.
Detection of Patients at Risk of Enterobacteriaceae Infection Using Graph Neural Networks: a Retrospective Study
Authors: Gouareb Racha , Bornet Alban , Proios Dimitrios , Pereira Sónia Gonçalves , Teodoro Douglas 
Published: June 2023

AbstractWhile Enterobacteriaceae bacteria are commonly found in healthy human gut, their colonisation of other body parts can potentially evolve into serious infections and health threats. We aim to design a graph-based machine learning model to assess risks of inpatient colonisation by multi-drug resistant (MDR) Enterobacteriaceae. The colonisation prediction problem was defined as a binary classification task, where the goal is to predict whether a patient is colonised by MDR Enterobacteriaceae in an undesirable body part during their hospital stay. To capture topological features, interactions among patients and healthcare workers were modelled using a graph structure, where patients are described by nodes and their interactions by edges. Then, a graph neural network (GNN) model was trained to learn colonisation patterns from the patient network enriched with clinical and spatiotemporal features. The GNN model predicts colonisation risk with an AUROC of 0.93 (95% CI: 0.92-0.94), 7% above a logistic regression baseline (0.86 [0.85-0.87]). Comparing different graph topologies, the configuration that considers only in-ward edges (0.93 [0.92-0.94]) outperforms the configurations that include only out-ward edges (0.86 [0.85-0.87]) and both edges (0.90 [0.89-0.91]). For the top-3 most prevalent MDR Enterobacteriaceae, the AUROC varies from 0.92 (0.90-0.93) forEscherichia coliup to 0.95 (0.92-0.98) forEnterobacter cloacae, using the GNN – in-ward model. Topological features via graph modelling improves the performance of machine learning models for Enterobacteriaceae colonisation prediction. GNNs could be used to support infection prevention and control programmes to detect patients at risk of colonisation by MDR Enterobacteriaceae and other bacteria families.
The effect of screening on the health burden of chlamydia: An evaluation of compartmental models based on person-days of infection
Authors: Farrell Jack , Spolyar Owen , Greenhalgh Scott 
Published: June 2023

AbstractSexually transmitted diseases are detrimental to the health and economic well-being of society. Consequently, predicting impending outbreaks and identifying effective disease interventions through the use of epidemiological tools, such as compartmental models, is of the utmost importance. Unfortunately, traditional compartmental models, specifically the differential equation models attributed to the work of Kermack and McKendrick, require either a duration of infection that follows the exponential or Erlang distribution, despite the biological invalidity of such assumptions. As these assumptions negatively impact the quality of model predictions, alternative approaches are required that capture the variability in the duration of infection, along with its associated effects on the trajectory of disease, and in the evaluation of disease interventions. So, we apply an entirely new family of differential equation compartmental models based on the quantity, “person-days of infection,” to predict the trajectory of a disease. Importantly, this new family of models can alternative duration of infection distributions. As proof of concept, we calibrate our model to recent trends of chlamydia incidence in the United States and utilize a general statistical distribution that features periodic hazard rates. We then evaluate how increasing sexually transmitted disease screening rates alter predictions of incidence and saves disability adjusted life-years over a 5-year horizon. Our findings illustrate that increasing the annual screening rate of chlamydia from 35% to 40%-70% would annually avert 6.1-40.3 incidence and 1.68-11.14 disability adjusted life-years per 1000 people. This suggests increasing the screening rate of sexually transmitted diseases in the United States would greatly aid in ongoing public health efforts to curtail the rising trends in preventable sexually transmitted diseases.
Benchmarking local genetic correlation estimation methods using summary statistics from genome-wide association studies
Authors: Zhang Chi , Zhang Yiliang , Zhang Yunxuan , Zhao Hongyu 
Published: June 2023

AbstractLocal genetic correlation evaluates the correlation of genetic effects between different traits across genetic variants in a local region. It has been proven informative for understanding the genetic similarities of complex traits beyond that captured by global genetic correlation calculated across the whole genome. Several summary-statistics-based approaches have been developed for estimating local genetic correlation, includingρ-hess, SUPERGNOVA, and LAVA. However, there has not been a comprehensive evaluation of these methods to offer practical guidelines on the choices of these methods. In this study, we conduct benchmark comparisons of the performance of these three methods through extensive simulation and real data analyses. We focus on two technical difficulties in estimating local genetic correlation: sample overlaps across traits and local linkage disequilibrium (LD) estimates when only the external reference panels are available. Our simulations suggest that the type-I error and estimation accuracy are highly dependent on the estimation of the local LD matrix. These observations are corroborated by real data analyses of 31 complex traits. Overall, our results offer insights into post-GWAS local correlation studies and highlight issues that demand future methodology developments.
Effect of mangrove-sword bean-food bar on weight and Weight-for-Age Z-score in under-five children after landslide disaster
Authors: Fatmah  , Utomo Suyud Warno 
Published: June 2023

AbstractSpecial attention needs to be given to under-five children who have specific needs due to their lower ability to prepare for disasters. Simple, ready-to-eat, and tasty food that meets the micronutrient needs of the groups is needed. The study aimed to assess the effect of the food bar made fromapi-apimangrove (Avicennia marina) and sword bean (Canavalia ensiformis) blends on the weight and Weight-for-Age Z (WAZ) score after landslide disaster. A non randomized pre-post intervention study was performed on 34 under-five children affected by landslide disaster during 15 days. Subjects were divided into intervention (api-apimangrove-sword beanfood bars) and control groups (sword bean food bars). Both groups received the food bars for 15 days. Education on balanced nutrition for under-five children was provided to all subjects’ mothers in the study. The study revealed that most mothers of under-five children liked mangrove-sword bean food bar from the aroma, taste, texture, and color in the hedonic test. The intervention group experienced weight gain (0.32 kg) and WAZ score (0.73) were greater compared with the control group. There were significant difference in weight and WAZ score changes of the under-five children accompanied by a significant increases in mothers’ knowledge on the balanced nutrition for under-five children and food bar total consumption. No significant differences of macronutrient consumption, except fat intake between pre-post study were found.Api-apimangrove-sword beanfood bar can be an emergency food alternative for disaster vulnerable group communities affected by natural disasters. Future studies may wish to consider examining the issue using pregnant women as the research subjects.
Neuronal expression of human amyloid-β and Tau drives global phenotypic and multi-omic changes inC. elegans
Authors: Holcom Angelina , Fuentealba Matias , Sivapatham Renuka , King Christina D. , Osman Hadley , Foulger Anna , Bhaumik Dipa , Schilling Birgit , Furman David , Andersen Julie K. , Lithgow Gordon J. 
Published: June 2023

AbstractAlzheimer’s disease (AD) and Alzheimer’s related diseases (ADRD) are prevalent age-related neurodegenerative disorders characterized by the accumulation of amyloid-β (Aβ) plaques and Tau neurofibrillary tangles. The nematodeCaenorhabditis elegans (C. elegans) serves as an invaluable model organism in diseases of old age-due to its rapid aging. Here we performed an unbiased systems analysis of aC. elegansstrain expressing both Aβ and Tau proteins within neurons. We set out to determine if there was a phenotypic interaction between Aβ and Tau. In addition, we were interested in determining the temporal order of the phenotypic and multi-omic (geromic) outcomes. At an early stage of adulthood, we observed reproductive impairments and mitochondrial dysfunction consistent with disruptions in mRNA transcript abundance, protein solubility, and metabolite levels. Notably, the expression of these neurotoxic proteins exhibited a synergistic effect, leading to accelerated aging. Our findings shed light on the close relationship between normal aging and ADRD. Specifically, we demonstrate alterations to metabolic functions preceding age-related neurotoxicity, offering a resource for the development of new therapeutic strategies.
Adult-onset CNS sulfatide deficiency causes sex-dependent metabolic disruption in aging
Authors: Qiu Shulan , He Sijia , Wang Jianing , Wang Hu , Bhattacharjee Anindita , Li Xin , Saeed Moawiz , Dupree Jeffrey L. , Han Xianlin 
Published: June 2023

AbstractThe interconnection between obesity and central nervous system (CNS) neurological dysfunction has been widely appreciated. Accumulating evidence demonstrates that obesity is a risk factor for CNS neuroinflammation and cognitive impairment. However, the extent to which CNS disruption influences peripheral metabolism remains to be elucidated. We previously reported that myelin-enriched sulfatide loss leads to CNS neuroinflammation and cognitive decline. In this study, we further investigated the impact of CNS sulfatide deficiency on peripheral metabolism while considering sex- and age-specific effects. We found that female sulfatide-deficient mice gained significantly more body weight, exhibited higher basal glucose levels, and were glucose intolerant during glucose-tolerance test (GTT) compared to age-matched controls under a normal diet, whereas male sulfatide-deficient mice only displayed glucose intolerance at a much older age compared to female sulfatide-deficient mice. Mechanistically, we found the increased body weight was associated with increased food intake and elevated neuroinflammation, especially in the hypo-thalamus, in a sex-specific manner. Our results suggest that CNS sulfatide deficiency leads to sex-specific alterations in energy homeostasis via dysregulated hypothalamic control of food-intake.