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Rasmussen, M. A.

Publications and source records attributed to Rasmussen, M. A..

15 recordsLinked to original sources

Agreement between Garmin and Ultrahuman wearables and their association with continuous glucose monitoring: an n-of-1 study

Background: Consumer wearables and continuous glucose monitors (CGM) are increasingly worn together outside clinical settings. Few studies have examined whether two wearables worn at the same time agree with each other, and whether either tracks glucose metrics derived from CGM. Objective: In one adult under free-living conditions, we examined (1) how well sleep, heart rate, heart rate variability (HRV) and activity metrics from a Garmin smartwatch and an Ultrahuman ring agreed with each other, and (2) how these metrics related to glucose measured by CGM. Methods: One healthy adult with no diagnosed diabetes wore a Garmin Fenix 8 watch on the wrist, an Ultrahuman Ring AIR and an Abbott FreeStyle Libre CGM at the same time for 12 days (29 July to 9 August 2026; 1101 glucose readings). We assessed agreement between the devices with Pearson correlation and Bland-Altman analysis (mean bias and 95% limits of agreement, LoA) for daily metrics and for heart rate within the day, and with Cohen's kappa for sleep stages, minute by minute. We related the wearable metrics to mean glucose, glucose variability (coefficient of variation, CV%) and time in range (TIR, 3.9 to 10.0 mmol/L), reading by reading (over the whole record and separately for sleep and waking hours) and day by day. All correlations are descriptive. Because the Ultrahuman ring recorded no data for 22 hours on 3 August and its daytime heart rate behaved differently afterwards, heart-rate analyses are reported for the whole period and separately before and after that gap. The daily results were checked by leaving out one day at a time and by excluding the first 24 hours of sensor wear. Results: The devices agreed closely on total sleep duration (r=0.94; bias -0.02 h, 95% LoA -0.56 to 0.51 h). Daily steps correlated strongly (r=0.99 over the 11 days with data from both devices), but Garmin counted more steps on every day (mean 11,157 vs. 8,929 steps per day; bias +2228 steps). Heart rate agreed moderately during sleep (r=0.68). While awake, agreement was moderate before the gap (r=0.54) and absent after it (r=0.08), when Ultrahuman's daytime heart rate stayed near 70 bpm. The devices assigned the same sleep stage in 50.0% of 4525 minutes (kappa=0.28). Mean glucose was 5.13 mmol/L (SD 0.82) and TIR was 97.5%. Of all wearable signals, heart rate was most closely associated with glucose (Garmin r=0.43 over all readings), but the correlation fell to 0.34 within sleep and 0.21 within waking hours, and before the gap the two devices' waking correlations were alike (Garmin 0.25, Ultrahuman 0.24). Across the 12 days, correlations between night-time wearable metrics and glucose variability weakened markedly when the first 24 hours of sensor wear were excluded (absolute r fell from 0.59 or more to 0.34 or less), and TIR was 100% on 8 of the 12 days, which left it little room to vary. Conclusions: The two wearables agreed on how long the participant slept but not on how the night was staged, and their heart-rate agreement depended on whether the participant was asleep or awake and on the period of wear. Of all wearable signals, heart rate was most closely associated with glucose, mainly because both are lower at night and higher during the day. The associations across days rested largely on the first night of sensor wear. In this single participant, the devices behaved differently by device and by period of wear, so studies that combine different wearables, or relate them to CGM, should check for such differences before pooling data.

physiology↗

Revealing Subject-Specific Temporal Patterns from Longitudinal Data

MotivationTemporal multivariate data is ubiquitous in many domains, for instance, being collected over time at planned visits (every few months/years) in longitudinal cohorts, or every few minutes/hours in challenge tests. The analysis of such data often focuses on revealing the underlying temporal patterns common across subjects. However, there are subject-specific differences in temporal patterns, which hold the promise to enhance our understanding of underlying mechanisms and facilitate personalized approaches. Nevertheless, extracting subject-specific temporal patterns from longitudinal multivariate data reliably is an open challenge. ResultsWe introduce coupled matrix factorizations (CMF) as effective tools to capture subject-specific temporal patterns focusing on two novel applications: analysis of longitudinal metabolomics data and sensitization data. Our analysis shows that CMF models reliably capture subject-specific (shape) differences in temporal patterns revealing further in-sights compared to the state of the art. In metabolomics, CMF models reveal differences in metabolic responses of individuals (in a postprandial meal challenge) according to anthropometric and insulin sensitivity measures. In sensitization data analysis, CMF-based methods capture differences in temporal trajectories of children according to delivery/birth mode. We demonstrate the reliability of extracted patterns using reproducibility and replicability. AvailabilityThe code is available on https://github.com/cchatzis/Revealing-Subject-specific-Temporal-Patterns-from-Longitudinal-Data. Clinical data is not publicly available due to privacy reasons. Data can be made available under a joint research collaboration by contacting COPSAC (administration@dbac.dk).

bioinformatics↗

Extracting host-specific developmental signatures from longitudinal microbiome data

Longitudinal microbiome studies provide critical insights into microbial community dynamics and their relation to host health. Tensor decompositions offer a powerful framework for the unsupervised analysis of such data, yielding interpretable low-dimensional temporal patterns. However, existing approaches based on the CANDECOMP/PARAFAC (CP) model assume common temporal dynamics for all subjects and therefore cannot capture subject-specific trajectories. To address this limitation, we introduce a novel analytical framework based on PARAFAC2 to explicitly model subject-specific variations, such as shifts and delays in temporal patterns. Through systematic comparisons on simulated and real-world datasets--including studies of infant gut maturation and dietary interventions--we demonstrate that PARAFAC2 outperforms CP in capturing subject-specific temporal trajectories, and enables the discovery of biologically relevant patterns that are overlooked by CP. Furthermore, we introduce replicability as a robust criterion for selecting the number of components and demonstrate that the extracted patterns are replicable. Author summaryLongitudinal microbiome datasets are complex, consisting of repeated high-dimensional compositions that track changes in microbial abundance across individuals over time. While tensor decompositions are powerful tools for unraveling structure in these data, standard models like CANDECOMP/PARAFAC (CP) impose a critical limitation: they assume that temporal dynamics are identical across all individuals. This assumption often fails to capture the heterogeneity of biological processes, such as the varying pace of gut microbiome maturation or distinct individual responses to dietary changes. In this work, we introduce a novel analytical framework leveraging the PARAFAC2 model to overcome these constraints. By explicitly modeling subject-specific temporal variations, our PARAFAC2-based approach allows for the detection of individual time shifts and delays. We validated this framework using both simulation and real-world cohorts, demonstrating its ability to recover personalized trajectories that CP obscures. Additionally, we implemented a robust criterion to guide model selection, ensuring that the discovered patterns are replicable.

bioinformatics↗

Matrix Matters: Context-Driven Metabolic Shifts in Bacillus cereus and Bacillus subtilis

Spore-forming Bacillus species, including pathogenic Bacillus cereus and spoilage-associated Bacillus subtilis, are major contributors to foodborne illness and product degradation. Understanding their metabolic behaviour in diverse food matrices is essential for improving risk assessment, spoilage prediction, and fermentation control. This study integrates isothermal microcalorimetry and targeted metabolomics to characterize the metabolic activity of B. cereus and B. subtilis in five nutrient sources: Brain Heart Infusion (BHI) medium, oat drink, milk, pea hydrolysate, and a combined oat-pea matrix. Metabolic heat production was monitored for 24 hours at 30{degrees}C. In BHI, B. cereus exhibited a shorter lag phase (mean {+/-} sd: 4.3 hours {+/-} 0.8) than B. subtilis (7.9 hours {+/-} 1.0) but produced less total heat. Across all food matrices, B. subtilis consistently generated more heat. The oat-pea matrix supported the highest calorimetric growth rates, surpassing oat or pea alone, and showed sugar depletion and accumulation of organic acids, indicating enhanced carbohydrate metabolism. Free amino acid release was matrix- and species-specific: B. subtilis had increased levels in oat, while B. cereus did so in pea. While B. cereus was metabolically active in all matrices, cereulide levels were matrix-dependent: 47.3 {+/-} 1.7 ng/mL in oat, 3.0 {+/-} 0.1 ng/mL in oat-pea, and undetectable in pea. These findings reveal clade-specific and matrix-driven metabolic strategies. This is the first study to combine calorimetry and metabolomics to evaluate Bacillus activity in plant-based and dairy matrices. This approach enhances our understanding of microbial physiology in complex food systems and provides a foundation for developing targeted strategies to improve food safety, stability, and product design.

microbiology↗

Metabolomic fingerprints of PAH exposure - identifying toxicological biomarkers in dynamically cultured 3D cell spheroids

Environmental exposure to polycyclic aromatic hydrocarbons (PAHs) causes metabolic dysfunction, but reliable biomarkers are still needed to assess human health effects. This study used 21-day matured human HepG2 spheroids, a metabolically competent three-dimensional (3D) liver model, to assess metabolic responses to graded, non-cytotoxic concentrations of benzo[a]pyrene (BaP) and benzo[b]fluoranthene (BBF) after 24- and 96-h exposure. Untargeted liquid chromatography-mass spectrometry (LC-MS) metabolomics, combined with multivariate and network analyses, identified compound- and time-specific metabolic signatures. At 24 hours, no metabolites showed significant changes. In contrast, at 96 hours, both PAHs consistently altered seven robust metabolites linked to polyamine metabolism, membrane dynamics, mitochondrial energy, and DNA-repair pathways. Network analysis showed BBF caused broader and more connected changes than BaP, indicating distinct toxicodynamics. These findings underscore the importance of extended exposure in revealing metabolic disruption and support a set of candidate biomarkers for future low-dose studies and improved risk assessment of airborne toxicants.

systems biology↗

Schistosoma mansoni-induced host immunopathology is gut microbiota dependent

Despite progress in schistosomiasis control during recent decades in endemic areas, this parasitic blood-fluke infection continues to pose a substantial public health burden. In depth understanding of the mechanisms behind the complex immunopathology and drivers of morbidity in schistosomiasis is urgently needed. Chronic infection with the parasitic blood fluke Schistosoma mansoni manifests the most severe pathology in relation to egg-induced host immune responses and fibrosis development. Host immune homeostasis is influenced by the commensal gut microbiota, which may therefore also affect systemic immunopathology induced by S. mansoni. Both humans and experimental animal models show metabolomic changes related to gut microbial and liver metabolism during S. mansoni infection, further supporting a link between gut microbiota and regulation of S. mansoni pathology. To investigate whether a radically changed gut microbiota composition would result in changed S. mansoni egg-induced pathology, a mouse model combining antibiotic treatment and infection was established. In the model, the commensal gut microbial composition of female C57BL/6-NTac mice was altered by oral administration of a broad-spectrum ampicillin-vancomycin cocktail prior to infection with S. mansoni and throughout the experiment. An ecosystem view of the host immune milieu was collated by measuring a wide range of parameters: gut microbiome characterisation, immune profiling on the transcriptional level (ileum and liver) supported by flow cytometry of cells (spleen and mesenteric lymph nodes) and bead-based measurements of immune parameters in sera, short-chain fatty acid measurements in sera and caecal content, intestinal permeability assessment, liver enzyme levels in sera, and histology and stereology to characterise immunopathology (ileum and liver). The application of stereological principles to address the non-spherical nature of egg-induced liver granulomas and ileum inflammation supported by liver enzyme levels, collagen deposition, and immune parameters, enabled demonstration of significantly less granuloma formation in livers from antibiotics treated mice compared to controls. The observed difference in the degree of egg-induced inflammatory response in livers from infected mice mediated by antibiotics treatment, was not observed in ileum tissue and could not be explained by infection burden. Our mouse model results demonstrate a role for the gut microbiota and intestinal immune milieu in regulation of systemic S. mansoni infection-driven liver pathology and, hence, potential morbidity. In translational context, these findings warrant that drivers of gut microbial changes and intestinal immune milieu must be considered when pursuing novel holistic interventions for treatment or alleviation of persistent schistosomiasis.

immunology↗

Longitudinal metabolomics data analysis informed bymechanistic models

MotivationMetabolomics measurements are noisy, often characterized by a small sample size and missing entries. While data-driven methods have shown promise in terms of analyzing metabolomics data, e.g., revealing biomarkers of various phenotypes, metabolomics data analysis can significantly benefit from incorporating prior information about metabolic mechanisms. In this paper, we introduce a novel data analysis approach where data-driven methods are guided by prior information through joint analysis of simulated data generated using a human metabolic model and real metabolomics measurements. ResultsWe arrange time-resolved metabolomics measurements of plasma samples collected during a meal challenge test from the COPSAC2000 cohort as a third-order tensor: subjects by metabolites by time samples. Simulated challenge test data generated using a human whole-body metabolic model is also arranged as a third-order tensor: virtual subjects by metabolites by time samples. Real and simulated data sets are coupled in the metabolites mode and jointly analyzed using coupled tensor factorizations to reveal the underlying patterns. Our experiments demonstrate that joint analysis of simulated and real data has a better performance in terms of pattern discovery achieving higher correlations with a BMI (body mass index)-related phenotype compared to the analysis of only real data in males while in females, the performance is comparable. We also demonstrate the advantages of such a joint analysis approach in the presence of incomplete measurements and its limitations in the presence of wrong prior information. AvailabilityThe code for joint analysis of real and simulated metabolomics data sets is released as a GitHub repository. Simulated data can also be accessed using the GitHub repo. Real measurements of plasma samples are not publicly available. Data may be shared by COPSAC through a collaboration agreement. Data access requests should be directed to Morten A. Rasmussen (morten.arendt@dbac.dk).

bioinformatics↗

Gut environmental factors explain variations in the gut microbiome composition and metabolism within and between healthy adults

The human gut microbiome is highly personal. However, the contribution of the gut environment to variations in the gut microbiome remains elusive. Here, we profiled the gut microbiome composition and metabolism over 9 consecutive days in 61 healthy adults and assessed gut environmental factors including segmental transit time and pH using a wireless motility capsule. Day-to-day fluctuations in gut environmental factors as well as segmental transit time and pH varied substantially between individuals. The gut environment explained more variations in gut microbiome and urine metabolome than dietary macronutrients or personal characteristics. Finally, we identified coffee-derived metabolites to be negatively correlated with small intestinal transit time and several microbial metabolites to be associated with colonic transit time including urinary proteolytic markers, faecal short-chain fatty acids, and breath methane. Our work suggests that the gut environment is key for understanding the individuality of the human gut microbiome composition and metabolism.

microbiology↗

A chemical structure and machine learning approach to assess the potential bioactivity of endogenous metabolites and their association with early-childhood hs-CRP levels

Metabolomics has gained much attraction due to its potential to reveal molecular disease mechanisms and present viable biomarkers. In this work we used a panel of untargeted serum metabolomes in 602 childhood patients of the COPSAC2010 mother-child cohort. The annotated part of the metabolome consists of 493 chemical compounds curated using automated procedures. Using predicted quantitative-structure-bioactivity relationships for the Tox21 database on nuclear receptors and stress response in cell lines, we created a filtering method for the vast number of quantified metabolites. The metabolites measured in childrens serums used here have predicted potential against the chosen target modelled targets. The targets from Tox21 have been used with quantitative structure-activity relationships (QSARs) and were trained for [~]7000 structures, saved as models, and then applied to 493 metabolites to predict their potential bioactivities. The models were selected based on strict accuracy criteria surpassing random effects. After application, 52 metabolites showed potential bioactivity based on structural similarity with known active compounds from the Tox21 set. The filtered compounds were subsequently used and weighted by their bioactive potential to show an association with early childhood hs-CRP levels at six months in a linear model supporting a physiological adverse effect on systemic low-grade inflammation. The significant metabolites were reported. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=103 SRC="FIGDIR/small/567095v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@9c0216org.highwire.dtl.DTLVardef@4d26fborg.highwire.dtl.DTLVardef@13a2f0corg.highwire.dtl.DTLVardef@e6cbd1_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

Characterizing human postprandial metabolic response using multiway data analysis

Analysis of time-resolved postprandial metabolomics data can enhance our knowledge about human metabolism by providing a better understanding of similarities and differences in postprandial responses of individuals, with the potential to advance precision nutrition and medicine. Traditional data analysis methods focus on clustering methods relying on summaries of data across individuals or use univariate methods analyzing one metabolite at a time. However, they fail to provide a compact summary revealing the underlying patterns, i.e., groups of subjects, clusters of metabolites, and their temporal profiles. In this study, we analyze NMR (Nuclear Magnetic Resonance) spectroscopy measurements of plasma samples collected at multiple time points during a meal challenge test from 299 individuals from the COPSAC2000 cohort. We arrange the data as a three-way array: subjects by metabolites by time, and use the CAN-DECOMP/PARAFAC (CP) tensor factorization model to capture the underlying patterns. We analyze the fasting state data to reveal static patterns of subject group differences, and the fasting state-corrected postprandial data to reveal dynamic markers of group differences. Our analysis demonstrates that the CP model reveals replicable and biologically meaningful patterns capturing certain metabolite groups and their temporal profiles, and showing differences among males according to their body mass index (BMI). Furthermore, we observe that certain lipoproteins relate to the group difference differently in the fasting vs. dynamic state in males. While similar dynamic patterns are observed in response to the challenge test in males and females, the BMI-related group difference is only observed in males in the dynamic state.

systems biology↗

Co-localization of antibiotic resistance genes is widespread in the infant gut microbiome and associates with an immature gut microbial composition

Even in the absence of antibiotic exposure, the gut microbiome of infants has been shown to contain numerous antibiotic resistance genes (ARGs), but the mechanism for this remains unclear. In environmental bacteria, the selective advantage of ARGs can be increased through co-localization with genes such as other ARGs, biocide resistance genes, metal resistance genes, and virulence genes. However, this phenomenon is unknown from the human gut microbiome during early life despite frequent exposures to biocides and metals from an early age. Here, we conducted a comprehensive analysis of genetic co-localization of resistance genes in a cohort of 662 Danish children and examined the association between such co-localization and environmental factors as well as gut microbial maturation. Our study showed that co-localization of ARGs with other resistance and virulence genes is common in the early gut microbiome and is associated with gut bacteria that are indicative of low maturity, especially E. coli. The most common forms of co-localization involved tetracycline and fluoroquinolone resistance genes located near other ARGs, and, on plasmids, co-localization predominantly occurred in the form of class 1 integrons. Antibiotic use caused a short-term increase in mobile ARGs, while non-mobile ARGs showed no significant change. Finally, we found that a high abundance of virulence genes was associated with low gut microbial maturity and that virulence genes showed even higher potential for mobility than ARGs. Our study highlights important constraints that need to be considered when developing strategies to combat ARG dissemination.

microbiology↗

Analyzing postprandial metabolomics data using multiway models: A simulation study

BackgroundAnalysis of time-resolved postprandial metabolomics data can improve the understanding of metabolic mechanisms, potentially revealing biomarkers for early diagnosis of metabolic diseases and advancing precision nutrition and medicine. Postprandial metabolomics measurements at several time points from multiple subjects can be arranged as a subjects by metabolites by time points array. Traditional analysis methods are limited in terms of revealing subject groups, related metabolites, and temporal patterns simultaneously from such three-way data. ResultsWe introduce an unsupervised multiway analysis approach based on the CANDECOMP/PARAFAC (CP) model for improved analysis of postpran-dial metabolomics data guided by a simulation study. Because of the lack of ground truth in real data, we generate simulated data using a comprehensive human metabolic model. This allows us to assess the performance of CP models in terms of revealing subject groups and underlying metabolic processes. We study three analysis approaches: analysis of fasting-state data using Principal Component Analysis, T0-corrected data (i.e., data corrected by subtracting fasting-state data) using a CP model and full-dynamic (i.e., full postprandial) data using CP. Through extensive simulations, we demonstrate that CP models capture meaningful and stable patterns from simulated meal challenge data, revealing underlying mechanisms and differences between diseased vs. healthy groups. ConclusionsOur experiments show that it is crucial to analyze both fasting-state and T0-corrected data for understanding metabolic differences among subject groups. Depending on the nature of the subject group structure, the best group separation may be achieved by CP models of T0-corrected or full-dynamic data. This study introduces an improved analysis approach for postprandial metabolomics data while also shedding light on the debate about correcting baseline values in longitudinal data analysis.

systems biology↗

Metaviromes reveal the dynamics of Pseudomonas host-specific phages cultured and uncultured by plaque assay

Isolating single phages using plaque assays is a laborious and time-consuming process. Whether single isolated phages are the most lyse-effective, the most abundant in viromes, or the ones with highest ability to plaque on solid media is not well known. With the increasing accessibility of high-throughput sequencing, metaviromics is often used to describe viruses in envi-ronmental samples. By extracting and sequencing metaviromes from organic waste with and without exposure to a host-of-interest, we show a host-related phage communitys shift, as well as identify the most enriched phages. Moreover, we isolated plaque-forming single phages using the same virome-host matrix to observe how enrichments in liquid media corresponds to the metaviromic data. In this study, we observed a significant shift (p = 0.015) of the 47 identified putative Pseudomonas phages with a minimum 2-fold change above 0 in read abundance when adding a Pseudomonas syringae DC3000 host. Surprisingly, it appears that only two out of five plaque-forming phages from the same organic waste sample, targeting the Pseudomonas strain, was highly abundant in the metavirome, while the other three were almost absent despite host exposure. Lastly, our sequencing results highlights how long reads from Oxford Nanopore elevates the assembly quality of metaviromes, compared to short reads alone.

microbiology↗

Stability of the vaginal microbiota during pregnancy and its importance for early infant colonization

Early life microbiota has been linked to the development of chronic inflammatory diseases. It has been hypothesized that maternal vaginal microbiota is an important initial seeding source and therefore can have lifelong effects on disease risk. To understand maternal vaginal microbiotas role in seeding the childs microbiota and the extent of delivery mode-dependent transmission, we studied 700 mother-child dyads from the COPSAC2010 cohort. The maternal vaginal microbiota was evaluated in the third trimester and compared with the childrens fecal and airway microbiota. The vaginal samples displayed known stable community state types and only 1:6 changed over time. Only one OTU was significantly transferred to childrens fecal compartment, but an inflated number had positive transfer odds. A few taxonomic families showed early transfer enrichment to vaginally-born children, indicating vertical transfer, while half of the observed transfer effects were delivery mode independent enrichment with attenuating strength over time, indicating a common reservoir.

bioinformatics↗

Kernel integration by Graphical LASSO

Integration of unstructured and very diverse data is often required for a deeper understanding of complex biological systems. In order to uncover communalities between heterogeneous data, the data is often harmonized by constructing a kernel and numerical integration is performed. In this study we propose a method for data integration in the framework of an undirected graphical model, where the nodes represent individual data sources of varying nature in terms of complexity and underlying distribution, and where the edges represent the partial correlation between two blocks of data. We propose a modified GLASSO for estimation of the graph, with a combination of cross-validation and extended Bayes Information Criterion for sparsity tuning. Furthermore, hierarchical clustering on the weighted consensus kernels from a fixed network is used to partitioning the samples into different classes. Simulations show increasing ability to uncover true edges with increasing sample size and signal to noise. Likewise, identification of non existing edges towards disconnected nodes is feasible. The framework is demonstrated for integration of longitudinal symptom burden data from the 2nd and 3rd year of life with 21 diseases precursors as well as the development of asthma and eczema at the age of 6 years from 403 children from the COPSAC2010 mother-child cohort, suggesting that maternal predisposition as well as being born preterm indirectly lead to higher risk of asthma via increased respiratory symptom burden.

bioinformatics↗