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In this study, we present MetaBakery (http://metabakery.fe.uni-lj.si), an integrated application designed as a framework for synergistically executing the bioBakery workflow and associated utilities. MetaBakery streamlines the processing of any number of paired or unpaired fastq files, or a mixture of both, with optional compression (gzip, zip, bzip2, xz, or mixed) within a single run. MetaBakery uses programs such as KneadData (https://github.com/bioBakery/kneaddata), MetaPhlAn, HUMAnN and StrainPhlAn as well as integrated utilities and extends the original functionality of bioBakery. In particular, it includes MelonnPan for the prediction of metabolites and Mothur for calculation of microbial alpha diversity. Written in Python 3 and C++ the whole pipeline was encapsulated as Singularity container for efficient execution on various computing infrastructures, including large High-Performance Computing clusters. MetaBakery facilitates crash recovery, efficient re-execution upon parameter changes, and processing of large data sets through subset handling and is offered in three editions with bioBakery ingredients versions 4, 3 and 2 as versatile, transparent and well documented within the MetaBakery Users' Manual (http://metabakery.fe.uni-lj.si/metabakery_manual.pdf). It provides automatic handling of command line parameters, file formats and comprehensive hierarchical storage of output to simplify navigation and debugging. MetaBakery filters out potential human contamination and excludes samples with low read counts. It calculates estimates of alpha diversity and represents a comprehensive and augmented re-implementation of the bioBakery workflow. The robustness and flexibility of the system enables efficient exploration of changing parameters and input datasets, increasing its utility for microbiome analysis. Furthermore, we have shown that the MetaBakery tool can be used in modern biostatistical and machine learning approaches including large-scale microbiome studies.
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The prevention of non-communicable diseases like cancer contributes to healthy aging. Dietary supplements might support such prevention; their effect likely depends on the personal characteristics of the individuals receiving them. To evaluate the influence of sex on reducing cancer incidence with multivitamin-multimineral (MVM) supplementation, sex-specific results of the efficacy of MVM supplementation for cancer prevention were collected and meta-analyzed (using fixed effect (FE) and random effect (RE) models). Three trials included in the "US Preventive Services Task Force Recommendation Statement Report regarding Vitamin, Mineral, and Multivitamin Supplementation to Prevent Cardiovascular Disease and Cancer" were used, namely, COSMOS, SU.VI.MAX, and PHS2. A total of 28,558 men and 20,542 women were included. Multivitamin-multimineral supplementation significantly reduced cancer incidence in the entire population (HR 0.93 [95% CI, 0.88-0.99], FE and RE); sex-specific meta-analysis showed beneficial effects of supplementation in men (HR 0.91 [95% CI, 0.85-0.97] (FE)/0.88 [95% CI, 0.77-1.01] (RE)); however, there was no effect in women (HR 1.00 [95% CI, 0.88-1.14], FR and RE); (Pdifference = 0.17). Sex could influence the effect of MVM supplementation in reducing cancer incidence, with supplementation being effective only in male individuals. These results might be informative for future research and public health policy makers.
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Enfermedades Cardiovasculares , Neoplasias , Masculino , Femenino , Humanos , Vitaminas , Suplementos Dietéticos , Minerales , Neoplasias/epidemiología , Neoplasias/prevención & controlRESUMEN
In this perspective analysis, we strive to answer the following question: how can we advance integrative biology research in the 21st century with lessons from animal science? At the University of Ljubljana, Biotechnical Faculty, Department of Animal Science, we share here our three lessons learned in the two decades from 2002 to 2022 that we believe could inform integrative biology, systems science, and animal science scholarship in other countries and geographies. Cultivating multiomics knowledge through a conceptual lens of integrative biology is crucial for life sciences research that can stand the test of diverse biological, clinical, and ecological contexts. Moreover, in an era of the current COVID-19 pandemic, animal nutrition and animal science, and the study of their interactions with human health (and vice versa) through integrative biology approaches hold enormous prospects and significance for systems medicine and ecosystem health.
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Disciplinas de las Ciencias Biológicas , COVID-19 , Animales , Humanos , Historia del Siglo XXI , Ecosistema , Pandemias , COVID-19/epidemiología , BiologíaRESUMEN
Physical inactivity is a worldwide health problem, an important risk for global mortality and is associated with chronic noncommunicable diseases. The aim of this study was to explore the differences in systemic urine 1H-NMR metabolomes between physically active and inactive healthy young males enrolled in the X-Adapt project in response to controlled exercise (before and after the 3-day exercise testing and 10-day training protocol) in normoxic (21% O2), normobaric (~1000 hPa) and normal-temperature (23 °C) conditions at 1 h of 50% maximal pedaling power output (Wpeak) per day. Interrogation of the exercise database established from past X-Adapt results showed that significant multivariate differences existed in physiological traits between trained and untrained groups before and after training sessions and were mirrored in significant differences in urine pH, salinity, total dissolved solids and conductivity. Cholate, tartrate, cadaverine, lysine and N6-acetyllisine were the most important metabolites distinguishing trained and untrained groups. The relatively little effort of 1 h 50% Wpeak per day invested by the untrained effectively modified their resting urine metabolome into one indistinguishable from the trained group, which hence provides a good basis for the planning of future recommendations for health maintenance in adults, irrespective of the starting fitness value. Finally, the 3-day sessions of morning urine samples represent a good candidate biological matrix for future delineations of active and inactive lifestyles detecting differences unobservable by single-day sampling due to day-to-day variability.
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Preterm birth (before 37 weeks gestation) accounts for ~10% of births worldwide and remains one of the leading causes of death in children under 5 years of age. Preterm born adults have been consistently shown to be at an increased risk for chronic disorders including cardiovascular, endocrine/metabolic, respiratory, renal, neurologic, and psychiatric disorders that result in increased death risk. Oxidative stress was shown to be an important risk factor for hypertension, metabolic syndrome and lung disease (reduced pulmonary function, long-term obstructive pulmonary disease, respiratory infections, and sleep disturbances). The aim of this study was to explore the differences between preterm and full-term male participants' levels of urine and fecal proton nuclear magnetic resonance (1H-NMR) metabolomes, during rest and exercise in normoxia and hypoxia and to assess general differences in human gut-microbiomes through metagenomics at the level of taxonomy, diversity, functional genes, enzymatic reactions, metabolic pathways and predicted gut metabolites. Significant differences existed between the two groups based on the analysis of 1H-NMR urine and fecal metabolomes and their respective metabolic pathways, enabling the elucidation of a complex set of microbiome related metabolic biomarkers, supporting the idea of distinct host-microbiome interactions between the two groups and enabling the efficient classification of samples; however, this could not be directed to specific taxonomic characteristics.
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General Unified Microbiome Profiling Pipeline (GUMPP) was developed for large scale, streamlined and reproducible analysis of bacterial 16S rRNA data and prediction of microbial metagenomes, enzymatic reactions and metabolic pathways from amplicon data. GUMPP workflow introduces reproducible data analyses at each of the three levels of resolution (genus; operational taxonomic units (OTUs); amplicon sequence variants (ASVs)). The ability to support reproducible analyses enables production of datasets that ultimately identify the biochemical pathways characteristic of disease pathology. These datasets coupled to biostatistics and mathematical approaches of machine learning can play a significant role in extraction of truly significant and meaningful information from a wide set of 16S rRNA datasets. The adoption of GUMPP in the gut-microbiota related research enables focusing on the generation of novel biomarkers that can lead to the development of mechanistic hypotheses applicable to the development of novel therapies in personalized medicine.
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Spinal muscular atrophy (SMA) is a genetically heterogeneous group of rare neuromuscular diseases and was until recently the most common genetic cause of death in children. The effects of 2-month nusinersen therapy on urine, serum, and liquor 1H-NMR metabolomes in SMA males and females were not explored yet, especially not in comparison to the urine 1H-NMR metabolomes of matching male and female cohorts. In this prospective, single-centered study, urine, serum, and liquor samples were collected from 25 male and female pediatric patients with SMA before and after 2 months of nusinersen therapy and urine samples from a matching healthy cohort (n = 125). Nusinersen intrathecal application was the first therapy for the treatment of SMA by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Metabolomes were analyzed using targeted metabolomics utilizing 600 MHz 1H-NMR, parametric and nonparametric multivariate statistical analyses, machine learning, and modeling. Medical assessment before and after nusinersen therapy showed significant improvements of movement, posture, and strength according to various medical tests. No significant differences were found in metabolomes before and after nusinersen therapy in urine, serum, and liquor samples using an ensemble of statistical and machine learning approaches. In comparison to a healthy cohort, 1H-NMR metabolomes of SMA patients contained a reduced number and concentration of urine metabolites and differed significantly between males and females as well. Significantly larger data scatter was observed for SMA patients in comparison to matched healthy controls. Machine learning confirmed urinary creatinine as the most significant, distinguishing SMA patients from the healthy cohort. The positive effects of nusinersen therapy clearly preceded or took place devoid of significant rearrangements in the 1H-NMR metabolomic makeup of serum, urine, and liquor. Urine creatinine was successful at distinguishing SMA patients from the matched healthy cohort, which is a simple systemic novelty linking creatinine and SMA to the physiology of inactivity and diabetes, and it facilitates the monitoring of SMA disease in pediatric patients through non-invasive urine collection.
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Past studies strongly connected stool consistency-as measured by Bristol Stool Scale (BSS)-with microbial gene richness and intestinal inflammation, colonic transit time and metabolome characteristics that are of clinical relevance in numerous gastro intestinal conditions. While retention time, defecation rate, BSS but not water activity have been shown to account for BSS-associated inflammatory effects, the potential correlation with the strength of a gel in the context of intestinal forces, abrasion, mucus imprinting, fecal pore clogging remains unexplored as a shaping factor for intestinal inflammation and has yet to be determined. Our study introduced a minimal pressure approach (MP) by probe indentation as measure of stool material crosslinking in fecal samples. Results reported here were obtained from 170 samples collected in two independent projects, including males and females, covering a wide span of moisture contents and BSS. MP values increased exponentially with increasing consistency (i.e., lower BSS) and enabled stratification of samples exhibiting mixed BSS classes. A trade-off between lowest MP and highest dry matter content delineated the span of intermediate healthy density of gel crosslinks. The crossectional transects identified fecal surface layers with exceptionally high MP and of <5 mm thickness followed by internal structures with an order of magnitude lower MP, characteristic of healthy stool consistency. The MP and BSS values reported in this study were coupled to reanalysis of the PlanHab data and fecal 1H-NMR metabolomes reported before. The exponential association between stool consistency and MP determined in this study was mirrored in the elevated intestinal and also systemic inflammation and other detrimental physiological deconditioning effects observed in the PlanHab participants reported before. The MP approach described in this study can be used to better understand fecal hardness and its relationships to human health as it provides a simple, fine scale and objective stool classification approach for the characterization of the exact sampling locations in future microbiome and metabolome studies.
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We explored the metabolic makeup of urine in prescreened healthy male participants within the PlanHab experiment. The run-in (5 day) and the following three 21-day interventions [normoxic bedrest (NBR), hypoxic bedrest (HBR), and hypoxic ambulation (HAmb)] were executed in a crossover manner within a controlled laboratory setup (medical oversight, fluid and dietary intakes, microbial bioburden, circadian rhythm, and oxygen level). The inspired O2 (FiO2) fraction next to inspired O2 (PiO2) partial pressure were 0.209 and 133.1 ± 0.3 mmHg for the NBR variant in contrast to 0.141 ± 0.004 and 90.0 ± 0.4 mmHg (approx. 4,000 m of simulated altitude) for HBR and HAmb interventions, respectively. 1H-NMR metabolomes were processed using standard quantitative approaches. A consensus of ensemble of multivariate analyses showed that the metabolic makeup at the start of the experiment and at HAmb endpoint differed significantly from the NBR and HBR endpoints. Inactivity alone or combined with hypoxia resulted in a significant reduction of metabolic diversity and increasing number of affected metabolic pathways. Sliding window analysis (3 + 1) unraveled that metabolic changes in the NBR lagged behind those observed in the HBR. These results show that the negative effects of cessation of activity on systemic metabolism are further aggravated by additional hypoxia. The PlanHab HAmb variant that enabled ambulation, maintained vertical posture, and controlled but limited activity levels apparently prevented the development of negative physiological symptoms such as insulin resistance, low-level systemic inflammation, constipation, and depression. This indicates that exercise apparently prevented the negative spiral between the host's metabolism, intestinal environment, microbiome physiology, and proinflammatory immune activities in the host.
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Microbial species play important roles in different environments and the production of high-quality genomes from metagenome data sets represents a major obstacle to understanding their ecological and evolutionary dynamics. Metagenome-Assembled Genomes Orchestra (MAGO) is a computational framework that integrates and simplifies metagenome assembly, binning, bin improvement, bin quality (completeness and contamination), bin annotation, and evolutionary placement of bins via detailed maximum-likelihood phylogeny based on multiple marker genes using different amino acid substitution models, next to average nucleotide identity analysis of genomes for delineation of species boundaries and operational taxonomic units. MAGO offers streamlined execution of the entire metagenomics pipeline, error checking, computational resource distribution and compatibility of data formats, governed by user-tailored pipeline processing. MAGO is an open-source-software package released in three different ways, as a singularity image and a Docker container for HPC purposes as well as for running MAGO on a commodity hardware, and a virtual machine for gaining a full access to MAGO underlying structure and source code. MAGO is open to suggestions for extensions and is amenable for use in both research and teaching of genomics and molecular evolution of genomes assembled from small single-cell projects or large-scale and complex environmental metagenomes.