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See detailForecasting of a complex microbial community using meta-omics
Delogu, Francesco UL; Kunath, Benoît UL; Queirós, P. M. et al

E-print/Working paper (2022)

Microbial communities are complex assemblages whose dynamics are shaped by abiotic and biotic factors. A major challenge concerns correctly forecasting the community behaviour in the future. In this ... [more ▼]

Microbial communities are complex assemblages whose dynamics are shaped by abiotic and biotic factors. A major challenge concerns correctly forecasting the community behaviour in the future. In this context, communities in biological wastewater treatment plants (BWWTPs) represent excellent model systems, because forecasting them is required to ultimately control and operate the plants in a sustainable manner. Here, we forecast the microbial community from the water-air interface of the anaerobic tank of a BWWTP via longitudinal meta-omics (metagenomics, metatranscriptomics and metaproteomics) data covering 14 months at weekly intervals. We extracted all the available time-dependent information, summarised it in 17 temporal signals (explaining 91.1 of the temporal variance) and linked them over time to rebuild the sequence of ecological phenomena behind the community dynamics. We forecasted the signals over the following five years and tested the predictions with 21 extra samples. We were able to correctly forecast five signals accounting for 22.5 of the time-dependent information in the system and generate mechanistic predictions on the ecological events in the community (e.g. a predation cycle involving bacteria, viruses and amoebas). Through the forecasting of the 17 signals and the environmental variables readings we reconstructed the gene abundance and expression for the following 5 years, showing a nearly perfect trend prediction (coefficient of determination >= 0.97) for the first 2 years. The study demonstrates the maturity of microbial ecology to forecast composition and gene expression of open microbial ecosystems using year-spanning interactions between community cycles and environmental parameters. [less ▲]

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

in Briefings in Bioinformatics (2022)

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

The reconstruction of genomes is a critical step in genome-resolved metagenomics and for multi-omic data integration from microbial communities. Here, we present binny, a binning tool that produces high-quality metagenome-assembled genomes (MAG) from both contiguous and highly fragmented genomes. Based on established metrics, binny outperforms or is highly competitive with commonly used and 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, nonlinear dimension reduction of genomic signatures as well as subsequent automated contig clustering with cluster assessment using lineage-specific marker gene sets. When compared with seven widely used binning algorithms, binny provides substantial amounts of uniquely identified MAGs and almost always recovers the most near-complete (⁠>95% pure, >90% complete) and high-quality (⁠>90% pure, >70% complete) genomes from simulated datasets from the Critical Assessment of Metagenome Interpretation initiative, as well as substantially more high-quality draft genomes, as defined by the Minimum Information about a Metagenome-Assembled Genome standard, from a real-world benchmark comprised of metagenomes from various environments than any other tested method. [less ▲]

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See detailMobilome-driven segregation of the resistome in biological wastewater treatment
de Nies, Laura UL; Busi, Susheel Bhanu UL; Kunath, Benoît UL et al

in eLife (2022), 11

Biological wastewater treatment plants (BWWTP) are considered to be hotspots of evolution and subsequent spread of antimicrobial resistance (AMR). Mobile genetic elements (MGEs) promote the mobilization ... [more ▼]

Biological wastewater treatment plants (BWWTP) are considered to be hotspots of evolution and subsequent spread of antimicrobial resistance (AMR). Mobile genetic elements (MGEs) promote the mobilization and dissemination of antimicrobial resistance genes (ARGs) and are thereby critical mediators of AMR within the BWWTP microbial community. At present, it is unclear whether specific AMR categories are differentially disseminated via bacteriophages (phages) or plasmids. To understand the segregation of AMR in relation to MGEs, we analyzed meta-omic (metagenomic, metatranscriptomic and metaproteomic) data systematically collected over 1.5 years from a BWWTP. Our results showed a core group of fifteen AMR categories which were found across all timepoints. Some of these AMR categories were disseminated exclusively (bacitracin) or primarily (aminoglycoside, MLS and sulfonamide) via plasmids or phages (fosfomycin and peptide), whereas others were disseminated equally by both MGEs. Combined and timepoint-specific analyses of gene, transcript and protein abundances further demonstrated that aminoglycoside, bacitracin and sulfonamide resistance genes were expressed more by plasmids, in contrast to fosfomycin and peptide AMR expression by phages, thereby validating our genomic findings. In the analyzed communities, the dominant taxon Candidatus Microthrix parvicella was a major contributor to several AMR categories whereby its plasmids primarily mediated aminoglycoside resistance. Importantly, we also found AMR associated with ESKAPEE pathogens within the BWWTP, for which MGEs also contributed differentially to the dissemination of ARGs. Collectively our findings pave the way towards understanding the segmentation of AMR within MGEs, thereby shedding new light on resistome populations and their mediators, essential elements that are of immediate relevance to human health. [less ▲]

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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 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 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 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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