References of "Wilmes, Paul 50003335"
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See detailStudying the Parkinson's disease metabolome and exposome in biological samples through different analytical and cheminformatics approaches: a pilot study
Talavera Andujar, Begona UL; Aurich, Dagny UL; Aho, Velma UL et al

in Analytical and Bioanalytical Chemistry (2022)

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease, with an increasing incidence in recent years due to the ageing population. Genetic mutations alone only explain <10% of PD ... [more ▼]

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease, with an increasing incidence in recent years due to the ageing population. Genetic mutations alone only explain <10% of PD cases, while environmental factors, including small molecules, may play a significant role in PD. In the present work, 22 plasma (11 PD, 11 control) and 19 feces samples (10 PD, 9 control) were analyzed by non-target high resolution mass spectrometry (NT-HRMS) coupled to two liquid chromatography (LC) methods (reversed phase (RP) and hydrophilic interaction liquid chromatography (HILIC)). A cheminformatics workflow was optimized using open software (MS-DIAL and patRoon) and open databases (all public MSP-formatted spectral libraries for MS-DIAL, PubChemLite for Exposomics and the LITMINEDNEURO list for patRoon). Furthermore, five disease-specific databases and three suspect lists (on PD and related disorders) were developed, using PubChem functionality to identifying relevant unknown chemicals. The results showed that non-target screening with the larger databases generally provided better results compared with smaller suspect lists. However, two suspect screening approaches with patRoon were also good options to study specific chemicals in PD. The combination of chromatographic methods (RP and HILIC) as well as two ionization modes (positive and negative) enhanced the coverage of chemicals in the biological samples. While most metabolomics studies in PD have focused on blood and cerebrospinal fluid, we found a higher number of relevant features in feces, such as alanine betaine or nicotinamide, which can be directly metabolized by gut microbiota. This highlights the potential role of gut dysbiosis in PD development. [less ▲]

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See detailThe gut microbial metabolite formate exacerbates colorectal cancer progression
Ternes, Dominik UL; Tsenkova, Mina UL; Pozdeev, Vitaly UL et al

in Nature Metabolism (2022)

The gut microbiome is a key player in the immunomodulatory and protumorigenic microenvironment during colorectal cancer (CRC), as different gut-derived bacteria can induce tumour growth. However, the ... [more ▼]

The gut microbiome is a key player in the immunomodulatory and protumorigenic microenvironment during colorectal cancer (CRC), as different gut-derived bacteria can induce tumour growth. However, the crosstalk between the gut microbiome and the host in relation to tumour cell metabolism remains largely unexplored. Here we show that formate, a metabolite produced by the CRC-associated bacterium Fusobacterium nucleatum, promotes CRC development. We describe molecular signatures linking CRC phenotypes with Fusobacterium abundance. Cocultures of F. nucleatum with patient-derived CRC cells display protumorigenic effects, along with a metabolic shift towards increased formate secretion and cancer glutamine metabolism. We further show that microbiome-derived formate drives CRC tumour invasion by triggering AhR signalling, while increasing cancer stemness. Finally, F. nucleatum or formate treatment in mice leads to increased tumour incidence or size, and Th17 cell expansion, which can favour proinflammatory profiles. Moving beyond observational studies, we identify formate as a gut-derived oncometabolite that is relevant for CRC progression. [less ▲]

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See detailIndividual factors and beliefs determining COVID-19 vaccination willingness
Pauly, Laure UL; Paccoud, Ivana UL; Satagopam, Venkata UL et al

Poster (2022, April)

Background: High vaccination coverage rates are necessary to reduce infections and transmissions of the SARS-CoV-2 virus causing COVID-19 and to allow successful mitigation of the current pandemic. To ... [more ▼]

Background: High vaccination coverage rates are necessary to reduce infections and transmissions of the SARS-CoV-2 virus causing COVID-19 and to allow successful mitigation of the current pandemic. To date, we are still lacking information to explain the hesitancy in Luxembourg towards uptake of the available COVID-19 vaccines. The present study explored motivations for and against vaccination in a population-representative sample of residents across Luxembourg to identify hesitant groups and develop strategies to increase population immunity against SARS-CoV-2. Methods: In the framework of the nationwide, representative longitudinal CON-VINCE study, a sample of 1589 respondents (49.6% women, 84.3% Luxembourg nationality) ranging from 18-84 years, participated in the survey in spring 2021. The protocol of the CON-VINCE study has been described in detail elsewhere (Snoeck et al. 2020). Results: 52% of the respondents had at least partial vaccination at time of assessment between April to June 2021. The most common reasons for vaccination of those willing to be vaccinated (81.2%) were altruistic motivations. Prevalent reasons against vaccination for those undecided (8.7%) or reluctant (10.2%) to be vaccinated were that the vaccine had not been tested sufficiently and the fear of long-term vaccine side effects. Only very few of the vaccination-hesitant or -reluctant respondents reported that they did not believe in vaccination in general. Conclusion: The present study identified motivations for and against COVID-19 vaccination and determined demographic and socio-economic factors associated with vaccination willingness. To increase vaccination rates, public health communication needs to target those unsure or unwilling to be vaccinated. We will continue to study the vaccination uptake in the Luxembourg population, as CON-VINCE is now part of the H2020-funded international ORCHESTRA project (https://orchestra-cohort.eu), research into comparing these results on a Pan-European level. [less ▲]

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See detailThe ecology of the unseen
Wilmes, Paul UL

in Archives des Sciences Naturelles, Physiques et Mathématiques (2022), XLVIII

On the global scale, humankind is having a profound impact on the ecology of assemblages of organisms which we can see with the naked eye. At the same time, we are also starting to learn about the impact ... [more ▼]

On the global scale, humankind is having a profound impact on the ecology of assemblages of organisms which we can see with the naked eye. At the same time, we are also starting to learn about the impact of our collective, modern lifestyles on the ecology of the unseen, for example the microbes in our gut which are being affected by the overuse of antibiotics and unhealthy diets. However, we do not fully understand which functions the microorganisms fulfill as our knowledge so far is rather limited. In our own research, we see for example that 50-90 % of the molecules produced by microbes are completely unknown to Science but likely play important roles in key physiological processes. This means that we as humans are presently affecting key microbial processes in our bodies without fully understanding the possible repercussions. In addition, many of these molecules likely have bioactive properties and, thereby, represent an untapped resource for the development of new drugs. Therefore, it is important that we start charting out this great molecular expanse to ensure its stewardship for generations to come. [less ▲]

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See detailTowards hypothesis-driven, personalized microbiome screening
Sedrani, Catherine Marie UL; Wilmes, Paul UL

in Cell Reports Methods (2022), 2(1),

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See detailParkinson's Disease progression, resilience and inflammation markers during the COVID-19 pandemic
Pauly, Claire UL; Glaab, Enrico UL; Hansen, Maxime UL et al

in Movement Disorders (2022), in press (doi: 10.1002/mds.29212)(in press),

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See detailAn archaeal compound as a driver of Parkinson’s disease pathogenesis
Trezzi, Jean-Pierre; Aho, Velma UL; Jäger, Christian UL et al

E-print/Working paper (2022)

Patients with Parkinson’s disease (PD) exhibit differences in their gut microbiomes compared to healthy individuals. Although differences have most commonly been described in the abundances of bacterial ... [more ▼]

Patients with Parkinson’s disease (PD) exhibit differences in their gut microbiomes compared to healthy individuals. Although differences have most commonly been described in the abundances of bacterial taxa, changes to viral and archaeal populations have also been observed. Mechanistic links between gut microbes and PD pathogenesis remain elusive but could involve molecules that promote α-synuclein aggregation. Here, we show that 2-hydroxypyridine (2-HP) represents a key molecule for the pathogenesis of PD. We observe significantly elevated 2-HP levels in faecal samples from patients with PD or its prodrome, idiopathic REM sleep behaviour disorder (iRBD), compared to healthy controls. 2-HP is correlated with the archaeal species Methanobrevibacter smithii and with genes involved in methane metabolism, and it is detectable in isolate cultures of M. smithii. We demonstrate that 2-HP is selectively toxic to transgenic α-synuclein overexpressing yeast and increases α-synuclein aggregation in a yeast model as well as in human induced pluripotent stem cell derived enteric neurons. It also exacerbates PD-related motor symptoms, α-synuclein aggregation, and striatal degeneration when injected intrastriatally in transgenic mice overexpressing human α-synuclein. Our results highlight the effect of an archaeal molecule in relation to the gut-brain axis, which is critical for the diagnosis, prognosis, and treatment of PD. [less ▲]

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See detailGastrische Interozeption und gastrische myoelektrische Aktivität bei chronisch-entzündlichen Darmerkrankungen und Reizdarmsyndrom
Schulz, André UL; Welsch, Sina; Etringer, Sarah et al

in Heinrichs, Markus; Schönauer, Monika (Eds.) 47. Jahrestagung Psychologie und Gehirn (2022)

Viszerale Hypersensitivität wird als zentraler Mechanismus bei chronisch-entzündlichen Darmerkrankungen (CED) und Reizdarmsyndrom (RDS) diskutiert, welche beide mit einer erheblichen Einschränkung der ... [more ▼]

Viszerale Hypersensitivität wird als zentraler Mechanismus bei chronisch-entzündlichen Darmerkrankungen (CED) und Reizdarmsyndrom (RDS) diskutiert, welche beide mit einer erheblichen Einschränkung der Lebensqualität einhergehen. Bisherige Studien verwenden zumeist invasive Verfahren, die jedoch typischerweise mit der Messung viszeraler Wahrnehmung interferieren. Diese Studie untersucht daher, ob CED und RDS mit einer veränderten Wahrnehmung „natürlicher“ (nicht-invasiver) gastrischer Dehnungen assoziiert sind („Interozeption“). Zwanzig CED-Patienten in Remission (13 Morbus Crohn, 7 Colitis Ulcerosa), 12 RDS-Patienten, sowie 20/12 parallelisierte gesunde Kontrollprobanden absolvierten den 2-stufigen Water-Load-Test, bei dem eine beliebige Menge Wasser getrunken wird, bis die subjektiven Schwelle der Sättigung (Stufe 1) und des Völlegefühls (Stufe 2) erreicht sind. Gastrische Motilität wurde mittels Elektrogastrographie untersucht. CED-Patienten tranken signifikant mehr Wasser bis zur Sättigungsschwelle als RDS-Patienten, während es keine Unterschiede zu den Kontrollgruppen gab. Die getrunkene Wassermenge bis zur Schwelle des Völlegefühls unterschied sich nicht zwischen den Gruppen. Die elektrogastrographischen Muster zeigten ebenfalls keine Gruppenunterschiede, was impliziert, dass es keine Pathologien in der gastrischen Motilität gab. Die getrunkene Wassermenge bis zur Sättigung korrelierte negativ mit darmbezogener Lebensqualität bei CED-Patienten, aber positiv mit emotionalem Wohlbefinden bei RDS-Patienten. Diese Ergebnisse legen eine relative gastrische Hypersensitivität bei RDS und eine relative gastrische Hyposensitivität bei CED nahe, was jeweils mit spezifischen Facetten der wahrgenommenen Lebensqualität assoziiert ist. [less ▲]

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See detailCombinatorial analysis reveals highly coordinated early-stage immune reactions that predict later antiviral immunity in mild COVID-19 patients
Capelle, Christophe M.; Ciré, Séverine; Domingues, Olivia et al

in Cell Reports Medicine (2022), 3(4), 100600

While immunopathology has been widely studied in patients with severe COVID-19, immune responses in non-hospitalized patients have remained largely elusive. We systematically analyze 484 peripheral ... [more ▼]

While immunopathology has been widely studied in patients with severe COVID-19, immune responses in non-hospitalized patients have remained largely elusive. We systematically analyze 484 peripheral cellular or soluble immune features in a longitudinal cohort of 63 mild and 15 hospitalized patients versus 14 asymptomatic and 26 household controls. We observe a transient increase of IP10/CXCL10 and interferon-β levels, coordinated responses of dominant SARS-CoV-2-specific CD4 and fewer CD8 T cells, and various antigen-presenting and antibody-secreting cells in mild patients within 3 days of PCR diagnosis. The frequency of key innate immune cells and their functional marker expression are impaired in hospitalized patients at day 1 of inclusion. T cell and dendritic cell responses at day 1 are highly predictive for SARS-CoV-2-specific antibody responses after 3 weeks in mild but not hospitalized patients. Our systematic analysis reveals a combinatorial picture and trajectory of various arms of the highly coordinated early-stage immune responses in mild COVID-19 patients. [less ▲]

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See detailbinny: an automated binning algorithm to recover high-quality genomes from complex metagenomic datasets 2021.12.22.473795
Hickl, Oskar UL; Teixeira Queiros, Pedro UL; Wilmes, Paul UL et al

E-print/Working paper (2021)

The reconstruction of genomes is a critical step in genome-resolved metagenomics as well as for multi-omic data integration from microbial communities. Here, we present binny, a binning tool that produces ... [more ▼]

The reconstruction of genomes is a critical step in genome-resolved metagenomics as well as for multi-omic data integration from microbial communities. Here, we present binny, a binning tool that produces high-quality metagenome-assembled genomes from both contiguous and highly fragmented genomes. Based on established metrics, binny outperforms existing state-of-the-art binning methods and finds unique genomes that could not be detected by other methods.binny uses k-mer-composition and coverage by metagenomic reads for iterative, non-linear dimension reduction of genomic signatures as well as subsequent automated contig clustering with cluster assessment using lineage-specific marker gene sets.When compared to five widely used binning algorithms, binny recovers the most near-complete (\>95 pure, \>90 complete) and high-quality (\>90 pure, \>70 complete) genomes from simulated data sets from the Critical Assessment of Metagenome Interpretation (CAMI) initiative, as well as from a real-world benchmark comprised of metagenomes from various environments. binny is implemented as Snakemake workflow and available from https://github.com/a-h-b/binny.Competing Interest StatementThe authors have declared no competing interest. [less ▲]

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See detailThe Metaproteomics Initiative: a coordinated approach for propelling the functional characterization of microbiomes
Van den Bossche, Tim; Arntzen, Magnus; Becher, Dörte et al

in Microbiome (2021), 9(1), 243

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See detailWhich demographic and socio-economic factors are associated with vaccination willingness and beliefs towards vaccination? Rapid report with first results
Leist, Anja UL; Klee, Matthias UL; Paccoud, Ivana UL et al

Report (2021)

In the framework of the CoVaLux project on vaccination and long COVID in Luxembourg, the project “Socio-economic determinants of long COVID and vaccination, and economic consequences with focus on labour ... [more ▼]

In the framework of the CoVaLux project on vaccination and long COVID in Luxembourg, the project “Socio-economic determinants of long COVID and vaccination, and economic consequences with focus on labour market and health care” aims to triangulate evidence from different data sources such as social security and general population data, the national cohort CON-VINCE as well as national health surveys. We seek to arrive at robust assessments of how socio-economic determinants shape vaccination willingness, occurrence, severity and persistence of long COVID, and economic consequences of long COVID in Luxembourg. [less ▲]

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See detailGenome Sequencing of SARS-CoV-2 Allows Monitoring of Variants of Concern through Wastewater
Herold, Malte; Fouquier d'herouël, Aymeric UL; May, Patrick UL et al

in Water (2021), 13(21 3018),

Monitoring SARS-CoV-2 in wastewater has shown to be an effective tool for epidemiological surveillance. More specifically, RNA levels determined with RT-qPCR have been shown to track with the infection ... [more ▼]

Monitoring SARS-CoV-2 in wastewater has shown to be an effective tool for epidemiological surveillance. More specifically, RNA levels determined with RT-qPCR have been shown to track with the infection dynamics within the population. However, the surveillance of individual lineages circulating in the population based on genomic sequencing of wastewater samples is challenging, as the genetic material constitutes a mixture of different viral haplotypes. Here, we identify specific signature mutations from individual SARS-CoV-2 lineages in wastewater samples to estimate lineages circulating in Luxembourg. We compare circulating lineages and mutations to those detected in clinical samples amongst infected individuals. We show that especially for dominant lineages, the allele frequencies of signature mutations correspond to the occurrence of particular lineages in the population. In addition, we provide evidence that regional clusters can also be discerned. We focused on the time period between November 2020 and March 2021 in which several variants of concern emerged and specifically traced the lineage B.1.1.7, which became dominant in Luxembourg during that time. During the subsequent time points, we were able to reconstruct short haplotypes, highlighting the co-occurrence of several signature mutations. Our results highlight the potential of genomic surveillance in wastewater samples based on amplicon short-read data. By extension, our work provides the basis for the early detection of novel SARS-CoV-2 variants. [less ▲]

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See detailMicrodiversity characterizes prevalent phylogenetic clades in the glacier-fed stream microbiome
Fodelianakis, Styliianos; Busi, Susheel Bhanu UL; Wilmes, Paul UL et al

in ISME Journal (2021)

Glacier-fed streams (GFSs) are extreme and rapidly vanishing ecosystems, and yet they harbor diverse microbial communities. Although our understanding of the GFS microbiome has recently increased, we do ... [more ▼]

Glacier-fed streams (GFSs) are extreme and rapidly vanishing ecosystems, and yet they harbor diverse microbial communities. Although our understanding of the GFS microbiome has recently increased, we do not know which microbial clades are ecologically successful in these ecosystems, nor do we understand potentially underlying mechanisms. Ecologically successful clades should be more prevalent across GFSs compared to other clades, which should be reflected as clade-wise distinctly low phylogenetic turnover. However, methods to assess such patterns are currently missing. Here we developed and applied a novel analytical framework, “phyloscore analysis”, to identify clades with lower spatial phylogenetic turnover than other clades in the sediment microbiome across twenty GFSs in New Zealand. These clades constituted up to 44% and 64% of community α-diversity and abundance, respectively. Furthermore, both their α-diversity and abundance increased as sediment chlorophyll a decreased, corroborating their ecological success in GFS habitats largely devoid of primary production. These clades also contained elevated levels of putative microdiversity than others, which could potentially explain their high prevalence in GFSs. This hitherto unknown microdiversity may be threatened as glaciers shrink, urging towards further genomic and functional exploration of the GFS microbiome. [less ▲]

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See detailFunctional meta-omics provide critical insights into long- and short-read assemblies
Galata, Valentina UL; Busi, Susheel Bhanu UL; Kunath, Benoît UL et al

in Briefings in Bioinformatics (2021)

Real-world evaluations of metagenomic reconstructions are challenged by distinguishing reconstruction artifacts from genes and proteins present in situ. Here, we evaluate short-read-only, long-read-only ... [more ▼]

Real-world evaluations of metagenomic reconstructions are challenged by distinguishing reconstruction artifacts from genes and proteins present in situ. Here, we evaluate short-read-only, long-read-only and hybrid assembly approaches on four different metagenomic samples of varying complexity. We demonstrate how different assembly approaches affect gene and protein inference, which is particularly relevant for downstream functional analyses. For a human gut microbiome sample, we use complementary metatranscriptomic and metaproteomic data to assess the metagenomic data-based protein predictions. Our findings pave the way for critical assessments of metagenomic reconstructions. We propose a reference-independent solution, which exploits the synergistic effects of multi-omic data integration for the in situ study of microbiomes using long-read sequencing data. [less ▲]

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See detailMantis: flexible and consensus-driven genome annotation
Teixeira Queiros, Pedro UL; Delogu, Francesco UL; Hickl, Oskar UL et al

in GigaScience (2021), 10(6),

The rapid development of the (meta-)omics fields has produced an unprecedented amount of high-resolution and high-fidelity data. Through the use of these datasets we can infer the role of previously ... [more ▼]

The rapid development of the (meta-)omics fields has produced an unprecedented amount of high-resolution and high-fidelity data. Through the use of these datasets we can infer the role of previously functionally unannotated proteins from single organisms and consortia. In this context, protein function annotation can be described as the identification of regions of interest (i.e., domains) in protein sequences and the assignment of biological functions. Despite the existence of numerous tools, challenges remain in terms of speed, flexibility, and reproducibility. In the big data era, it is also increasingly important to cease limiting our findings to a single reference, coalescing knowledge from different data sources, and thus overcoming some limitations in overly relying on computationally generated data from single sources.We implemented a protein annotation tool, Mantis, which uses database identifiers intersection and text mining to integrate knowledge from multiple reference data sources into a single consensus-driven output. Mantis is flexible, allowing for the customization of reference data and execution parameters, and is reproducible across different research goals and user environments. We implemented a depth-first search algorithm for domain-specific annotation, which significantly improved annotation performance compared to sequence-wide annotation. The parallelized implementation of Mantis results in short runtimes while also outputting high coverage and high-quality protein function annotations.Mantis is a protein function annotation tool that produces high-quality consensus-driven protein annotations. It is easy to set up, customize, and use, scaling from single genomes to large metagenomes. Mantis is available under the MIT license at https://github.com/PedroMTQ/mantis. [less ▲]

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See detailEmulating the gut–liver axis: Dissecting the microbiome's effect on drug metabolism using multiorgan-on-chip models
Lucchetti, Mara UL; Kaminska, Mathilda; Kehinde Oluwasegun, Aina et al

in Current Opinion in Endocrine and Metabolic Research (2021)

The homeostatic relationship between the gut, its microbiome, and the liver is crucial for the regulation of drug metabolism processes. Gut microbes are known to influence human health and disease by ... [more ▼]

The homeostatic relationship between the gut, its microbiome, and the liver is crucial for the regulation of drug metabolism processes. Gut microbes are known to influence human health and disease by enhancing food metabolism and providing a first line of defense against pathogens. In addition to this, the gut microbiome also plays a key role in the processing of exogenous pharmaceutical compounds. Modeling the highly variable luminal gut environment and understanding how gut microbes can modulate drug availability or induce liver toxicity remains a challenge. However, microfluidics-based technologies such as organ-on-chips could overcome current challenges in drug toxicity assessment assays because these technologies are able to better recapitulate complex human responses. Efforts are being made to create in vitro multiorgan platforms, tailored for an individual patient's microbial background. These platforms could be used as a tool to predict the effect of the gut microbiome on pharmacokinetics in a personalized way. [less ▲]

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See detailUnification of functional annotation descriptions using text mining
Teixeira Queiros, Pedro UL; Novikova, Polina UL; Wilmes, Paul UL et al

in Biological Chemistry (2021)

A common approach to genome annotation involves the use of homology-based tools for the prediction of the functional role of proteins. The quality of functional annotations is dependent on the reference ... [more ▼]

A common approach to genome annotation involves the use of homology-based tools for the prediction of the functional role of proteins. The quality of functional annotations is dependent on the reference data used, as such, choosing the appropriate sources is crucial. Unfortunately, no single reference data source can be universally considered the gold standard, thus using multiple references could potentially increase annotation quality and coverage. However, this comes with challenges, particularly due to the introduction of redundant and exclusive annotations. Through text mining it is possible to identify highly similar functional descriptions, thus strengthening the confidence of the final protein functional annotation and providing a redundancy-free output. Here we present UniFunc, a text mining approach that is able to detect similar functional descriptions with high precision. UniFunc was built as a small module and can be independently used or integrated into protein function annotation pipelines. By removing the need to individually analyse and compare annotation results, UniFunc streamlines the complementary use of multiple reference datasets. [less ▲]

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