ORCID Profile
0000-0001-8587-4177
Current Organisation
European Molecular Biology Laboratory
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Publisher: Springer Science and Business Media LLC
Date: 09-2022
DOI: 10.1038/S41591-022-01913-0
Abstract: Fecal microbiota transplantation (FMT) is a therapeutic intervention for inflammatory diseases of the gastrointestinal tract, but its clinical mode of action and subsequent microbiome dynamics remain poorly understood. Here we analyzed metagenomes from 316 FMTs, s led pre and post intervention, for the treatment of ten different disease indications. We quantified strain-level dynamics of 1,089 microbial species, complemented by 47,548 newly constructed metagenome-assembled genomes. Donor strain colonization and recipient strain resilience were mostly independent of clinical outcomes, but accurately predictable using LASSO-regularized regression models that accounted for host, microbiome and procedural variables. Recipient factors and donor–recipient complementarity, encompassing entire microbial communities to in idual strains, were the main determinants of strain population dynamics, providing insights into the underlying processes that shape the post-FMT gut microbiome. Applying an ecology-based framework to our findings indicated parameters that may inform the development of more effective, targeted microbiome therapies in the future, and suggested how patient stratification can be used to enhance donor microbiota colonization or the displacement of recipient microbes in clinical practice.
Publisher: Cold Spring Harbor Laboratory
Date: 15-08-2019
DOI: 10.1101/735696
Abstract: Microbial organisms inhabit virtually all environments and encompass a vast biological ersity. The pan-genome concept aims to facilitate an understanding of ersity within defined phylogenetic groups. Hence, pan-genomes are increasingly used to characterize the strain ersity of prokaryotic species. To understand the interdependency of pan-genome features (such as numbers of core and accessory genes) and to study the impact of environmental and phylogenetic constraints on the evolution of conspecific strains, we computed pan-genomes for 155 phylogenetically erse species using 7000 high-quality genomes. We show that many pan-genome features such as functional ersity and core genome nucleotide ersity are correlated to each other. Further, habitat flexibility as approximated by species ubiquity is associated with several pan-genome features, particularly core genome size. In general, environment had a stronger impact on pan-genome features than phylogenetic signal. Similar environmental preferences led to convergent evolution of pan-genomic features in distant phylogenetic clades. For ex le, the soil environment promotes expansion of pan-genome size, while host-associated habitats lead to its reduction.
Publisher: Springer Science and Business Media LLC
Date: 17-05-2021
DOI: 10.1186/S13059-021-02368-1
Abstract: treeclimbR is for analyzing hierarchical trees of entities, such as phylogenies or cell types, at different resolutions. It proposes multiple candidates that capture the latent signal and pinpoints branches or leaves that contain features of interest, in a data-driven way. It outperforms currently available methods on synthetic data, and we highlight the approach on various applications, including microbiome and microRNA surveys as well as single-cell cytometry and RNA-seq datasets. With the emergence of various multi-resolution genomic datasets, treeclimbR provides a thorough inspection on entities across resolutions and gives additional flexibility to uncover biological associations.
Publisher: Springer Science and Business Media LLC
Date: 08-12-2021
DOI: 10.1038/S41586-021-04177-9
Abstract: During the transition from a healthy state to cardiometabolic disease, patients become heavily medicated, which leads to an increasingly aberrant gut microbiome and serum metabolome, and complicates biomarker discovery
Publisher: Cold Spring Harbor Laboratory
Date: 28-12-2018
DOI: 10.1101/507194
Abstract: The gastrointestinal tract is abundantly colonized by microbes, yet the translocation of oral species to the intestine is considered a rare aberrant event, and a hallmark of disease. By studying salivary and fecal microbial strain populations of 310 species in 470 in iduals from five countries, we found that transmission to, and subsequent colonization of, the large intestine by oral microbes is common and extensive among healthy in iduals. We found evidence for a vast majority of oral species to be transferable, with increased levels of transmission in colorectal cancer and rheumatoid arthritis patients and, more generally, for species described as opportunistic pathogens. This establishes the oral cavity as an endogenous reservoir for gut microbial strains, and oral-fecal transmission as an important process that shapes the gastrointestinal microbiome in health and disease.
Publisher: Springer Science and Business Media LLC
Date: 19-04-2018
Publisher: eLife Sciences Publications, Ltd
Date: 12-02-2019
DOI: 10.7554/ELIFE.42693
Abstract: The gastrointestinal tract is abundantly colonized by microbes, yet the translocation of oral species to the intestine is considered a rare aberrant event, and a hallmark of disease. By studying salivary and fecal microbial strain populations of 310 species in 470 in iduals from five countries, we found that transmission to, and subsequent colonization of, the large intestine by oral microbes is common and extensive among healthy in iduals. We found evidence for a vast majority of oral species to be transferable, with increased levels of transmission in colorectal cancer and rheumatoid arthritis patients and, more generally, for species described as opportunistic pathogens. This establishes the oral cavity as an endogenous reservoir for gut microbial strains, and oral-fecal transmission as an important process that shapes the gastrointestinal microbiome in health and disease.
Publisher: Springer Science and Business Media LLC
Date: 02-2022
DOI: 10.1038/S41591-022-01688-4
Abstract: Previous microbiome and metabolome analyses exploring non-communicable diseases have paid scant attention to major confounders of study outcomes, such as common, pre-morbid and co-morbid conditions, or polypharmacy. Here, in the context of ischemic heart disease (IHD), we used a study design that recapitulates disease initiation, escalation and response to treatment over time, mirroring a longitudinal study that would otherwise be difficult to perform given the protracted nature of IHD pathogenesis. We recruited 1,241 middle-aged Europeans, including healthy in iduals, in iduals with dysmetabolic morbidities (obesity and type 2 diabetes) but lacking overt IHD diagnosis and in iduals with IHD at three distinct clinical stages—acute coronary syndrome, chronic IHD and IHD with heart failure—and characterized their phenome, gut metagenome and serum and urine metabolome. We found that about 75% of microbiome and metabolome features that distinguish in iduals with IHD from healthy in iduals after adjustment for effects of medication and lifestyle are present in in iduals exhibiting dysmetabolism, suggesting that major alterations of the gut microbiome and metabolome might begin long before clinical onset of IHD. We further categorized microbiome and metabolome signatures related to prodromal dysmetabolism, specific to IHD in general or to each of its three subtypes or related to escalation or de-escalation of IHD. Discriminant analysis based on specific IHD microbiome and metabolome features could better differentiate in iduals with IHD from healthy in iduals or metabolically matched in iduals as compared to the conventional risk markers, pointing to a pathophysiological relevance of these features.
Publisher: Cold Spring Harbor Laboratory
Date: 16-12-2020
DOI: 10.1101/2020.12.16.422776
Abstract: Genomes are critical units in microbiology, yet ascertaining quality in prokaryotic genomes remains a formidable challenge. We present GUNC (the Genome UNClutterer), a tool that accurately detects and quantifies genome chimerism based on the lineage homogeneity of in idual contigs using a genome’s full complement of genes. GUNC complements existing approaches by targeting previously underdetected types of contamination: we conservatively estimate that 5.7% of genomes in GenBank, 5.2% in RefSeq, and 15-30% of pre-filtered ‘high quality’ metagenome-assembled genomes in recent studies are undetected chimeras. GUNC provides a fast and robust tool to substantially improve prokaryotic genome quality. Source code (GPLv3+): rp-bork/gunc
Publisher: Springer Science and Business Media LLC
Date: 13-06-2021
DOI: 10.1186/S13059-021-02393-0
Abstract: Genomes are critical units in microbiology, yet ascertaining quality in prokaryotic genome assemblies remains a formidable challenge. We present GUNC (the Genome UNClutterer), a tool that accurately detects and quantifies genome chimerism based on the lineage homogeneity of in idual contigs using a genome’s full complement of genes. GUNC complements existing approaches by targeting previously underdetected types of contamination: we conservatively estimate that 5.7% of genomes in GenBank, 5.2% in RefSeq, and 15–30% of pre-filtered “high-quality” metagenome-assembled genomes in recent studies are undetected chimeras. GUNC provides a fast and robust tool to substantially improve prokaryotic genome quality.
Publisher: Springer Science and Business Media LLC
Date: 04-03-2019
DOI: 10.1038/S41467-019-08844-4
Abstract: Metagenomic sequencing has greatly improved our ability to profile the composition of environmental and host-associated microbial communities. However, the dependency of most methods on reference genomes, which are currently unavailable for a substantial fraction of microbial species, introduces estimation biases. We present an updated and functionally extended tool based on universal (i.e., reference-independent), phylogenetic marker gene (MG)-based operational taxonomic units (mOTUs) enabling the profiling of microbial species. As more than 30% of them could not previously be quantified at this taxonomic resolution, relative abundance estimates based on mOTUs are more accurate compared to other methods. As a new feature, we show that mOTUs, which are based on essential housekeeping genes, are demonstrably well-suited for quantification of basal transcriptional activity of community members. Furthermore, single nucleotide variation profiles estimated using mOTUs reflect those from whole genomes, which allows for comparing microbial strain populations (e.g., across different human body sites).
Publisher: eLife Sciences Publications, Ltd
Date: 31-12-2018
Publisher: Cold Spring Harbor Laboratory
Date: 09-06-2020
DOI: 10.1101/2020.06.08.140608
Abstract: The arrangement of hypotheses in a hierarchical structure (e.g., phylogenies, cell types) appears in many research fields and indicates different resolutions at which data can be interpreted. A common goal is to find a representative resolution that gives high sensitivity to identify relevant entities (e.g., microbial taxa or cell subpopulations) that are related to a phenotypic outcome (e.g. disease status) while controlling false detections, therefore providing a more compact view of detected entities and summarizing characteristics shared among them. Current methods, either performing hypothesis tests at an arbitrary resolution or testing hypotheses at all possible resolutions leading to nested results, are suboptimal. Moreover, they are not flexible enough to work in situations where each entity has multiple features to consider and different resolutions might be required for different features. For ex le, in single cell RNA-seq data, an increasing focus is to find differential state genes that change expression within a cell subpopulation in response to an external stimulus. Such differential expression might occur at different resolutions (e.g., all cells or a small set of cells) for different genes. Our new algorithm treeclimbR is designed to fill this gap by exploiting a hierarchical tree of entities, proposing multiple candidates that capture the latent signal and pinpointing branches or leaves that contain features of interest, in a data-driven way. It outperforms currently available methods on synthetic data, and we highlight the approach on various applications, including microbiome and microRNA surveys as well as single cell cytometry and RNA-seq datasets. With the emergence of various multi-resolution genomic datasets, treeclimbR provides a thorough inspection on entities across resolutions and gives additional flexibility to uncover biological associations.
Publisher: Cold Spring Harbor Laboratory
Date: 31-08-2023
Publisher: Oxford University Press (OUP)
Date: 28-10-2023
DOI: 10.1093/NAR/GKAD943
Publisher: Cold Spring Harbor Laboratory
Date: 27-01-2022
DOI: 10.1101/2022.01.26.477801
Abstract: Most microbes on our planet remain uncultured and poorly studied. Recent efforts to catalog their genetic ersity have revealed that a significant fraction of the observed microbial genes are functional and evolutionary untraceable, lacking homologs in reference databases. Despite their potential biological value, these apparently unrelated orphan genes from uncultivated taxa have been routinely discarded in metagenomics surveys. Here, we analyzed a global multi-habitat dataset covering 151,697 medium and high-quality metagenome assembled genomes (MAGs), 5,969 single- lified genomes (SAGs), and 19,642 reference genomes, and identified 413,335 highly curated novel protein families under strong purifying selection out of previously considered orphan genes. These new protein families, representing a three-fold increase over the total number of prokaryotic orthologous groups described to date, spread out across the prokaryote phylogeny, can span multiple habitats, and are notably overrepresented in recently discovered taxa. By genomic context analysis, we pinpointed thousands of unknown protein families to phylogenetically conserved operons linked to energy production, xenobiotic metabolism and microbial resistance. Most remarkably, we found 980 previously neglected protein families that can accurately distinguish entire uncultivated phyla, classes, and orders, likely representing synapomorphic traits that fostered their ergence. The systematic curation and evolutionary analysis of the unique genetic repertoire of uncultivated taxa opens new avenues for understanding the biology and ecological roles of poorly explored lineages at a global scale.
Publisher: Oxford University Press (OUP)
Date: 24-10-2019
DOI: 10.1093/NAR/GKZ1002
Abstract: Microbiology depends on the availability of annotated microbial genomes for many applications. Comparative genomics approaches have been a major advance, but consistent and accurate annotations of genomes can be hard to obtain. In addition, newer concepts such as the pan-genome concept are still being implemented to help answer biological questions. Hence, we present proGenomes2, which provides 87 920 high-quality genomes in a user-friendly and interactive manner. Genome sequences and annotations can be retrieved in idually or by taxonomic clade. Every genome in the database has been assigned to a species cluster and most genomes could be accurately assigned to one or multiple habitats. In addition, general functional annotations and specific annotations of antibiotic resistance genes and single nucleotide variants are provided. In short, proGenomes2 provides threefold more genomes, enhanced habitat annotations, updated taxonomic and functional annotation and improved linkage to the NCBI BioS le database. The database is available at progenomes.embl.de/.
Publisher: Cold Spring Harbor Laboratory
Date: 30-09-2021
DOI: 10.1101/2021.09.30.462010
Abstract: Faecal microbiota transplantation (FMT) is an efficacious therapeutic intervention, but its clinical mode of action and underlying microbiome dynamics remain poorly understood. Here, we analysed the metagenomes associated with 142 FMTs, in a time series-based meta-study across five disease indications. We quantified strain-level dynamics of 1,089 microbial species based on their pangenome, complemented with 47,548 newly constructed metagenome-assembled genomes. Using subsets of procedural-, host- and microbiome-based variables, LASSO-regularised regression models accurately predicted the colonisation and resilience of donor and recipient microbes, as well as turnover of in idual species. Linking this to putative ecological mechanisms, we found these sets of variables to be informative of the underlying processes that shape the post-FMT gut microbiome. Recipient factors and complementarity of donor and recipient microbiomes, encompassing entire communities to in idual strains, were the main determinants of in idual strain population dynamics, and mostly independent of clinical outcomes. Recipient community state and the degree of residual strain depletion provided a neutral baseline for donor strain colonisation success, in addition to inhibitive priority effects between species and conspecific strains, as well as putatively adaptive processes. Our results suggest promising tunable parameters to enhance donor flora colonisation or recipient flora displacement in clinical practice, towards the development of more targeted and personalised therapies.
Publisher: Springer Science and Business Media LLC
Date: 15-12-2021
DOI: 10.1038/S41586-021-04233-4
Abstract: Microbial genes encode the majority of the functional repertoire of life on earth. However, despite increasing efforts in metagenomic sequencing of various habitats
Publisher: Cold Spring Harbor Laboratory
Date: 23-07-2018
DOI: 10.1101/374298
Abstract: The smallest members of the sunlit-ocean microbiome (prokaryotes and picoeukaryotes) participate in a plethora of ecosystem functions with planetary-scale effects. Understanding the processes determining the spatial turnover of this assemblage can help us better comprehend the links between microbiome species composition and ecosystem function. Ecological theory predicts that selection , dispersal and drift are main drivers of species distributions, yet, the relative quantitative importance of these ecological processes in structuring the surface-ocean microbiome is barely known. Here we quantified the role of selection, dispersal and drift in structuring surface-ocean prokaryotic and picoeukaryotic assemblages by using community DNA-sequence data collected during the global Malaspina expedition. We found that dispersal limitation was the dominant process structuring picoeukaryotic communities, while a balanced combination of dispersal limitation, selection and drift shaped prokaryotic counterparts. Subsequently, we determined the agents exerting abiotic selection as well as the spatial patterns emerging from the action of different ecological processes. We found that selection exerted via temperature had a strong influence on the structure of prokaryotic communities, particularly on species co-occurrences, a pattern not observed among communities of picoeukaryotes. Other measured abiotic variables had limited selective effects on microbiome structure. Picoeukaryotes presented a higher differentiation between neighbouring communities and a higher distance-decay when compared to prokaryotes, agreeing with their higher dispersal limitation. Finally, drift seemed to have a limited role in structuring the sunlit-ocean microbiome. The different predominance of ecological processes acting on particular subsets of the ocean microbiome suggests uneven responses to environmental change. The global ocean contains one of the largest microbiomes on Earth and changes on its structure can impact the functioning of the biosphere. Yet, we are far from understanding the mechanisms that structure the global ocean microbiome, that is, the relative importance of environmental selection , dispersal and random events ( drift ). We evaluated the role of these processes at the global scale, based on data derived from a circumglobal expedition and found that these ecological processes act differently on prokaryotes and picoeukaryotes, two of the main components of the ocean microbiome. Our work represents a significant contribution to understand the assembly of marine microbial communities, providing also insights on the links between ecological mechanisms, microbiome structure and ecosystem function.
Publisher: Springer Science and Business Media LLC
Date: 20-04-2020
DOI: 10.1186/S40168-020-00827-8
Abstract: The ocean microbiota modulates global biogeochemical cycles and changes in its configuration may have large-scale consequences. Yet, the underlying ecological mechanisms structuring it are unclear. Here, we investigate how fundamental ecological mechanisms ( selection , dispersal and ecological drift ) shape the smallest members of the tropical and subtropical surface-ocean microbiota: prokaryotes and minute eukaryotes (picoeukaryotes). Furthermore, we investigate the agents exerting abiotic selection on this assemblage as well as the spatial patterns emerging from the action of ecological mechanisms. To explore this, we analysed the composition of surface-ocean prokaryotic and picoeukaryotic communities using DNA-sequence data (16S- and 18S-rRNA genes) collected during the circumglobal expeditions Malaspina - 2010 and TARA - Oceans . We found that the two main components of the tropical and subtropical surface-ocean microbiota, prokaryotes and picoeukaryotes, appear to be structured by different ecological mechanisms. Picoeukaryotic communities were predominantly structured by dispersal-limitation, while prokaryotic counterparts appeared to be shaped by the combined action of dispersal-limitation, selection and drift. Temperature-driven selection appeared as a major factor, out of a few selected factors, influencing species co-occurrence networks in prokaryotes but not in picoeukaryotes, indicating that association patterns may contribute to understand ocean microbiota structure and response to selection. Other measured abiotic variables seemed to have limited selective effects on community structure in the tropical and subtropical ocean. Picoeukaryotes displayed a higher spatial differentiation between communities and a higher distance decay when compared to prokaryotes, consistent with a scenario of higher dispersal limitation in the former after considering environmental heterogeneity. Lastly, random dynamics or drift seemed to have a more important role in structuring prokaryotic communities than picoeukaryotic counterparts. The differential action of ecological mechanisms seems to cause contrasting biogeography, in the tropical and subtropical ocean, among the smallest surface plankton, prokaryotes and picoeukaryotes. This suggests that the idiosyncrasy of the main constituents of the ocean microbiota should be considered in order to understand its current and future configuration, which is especially relevant in a context of global change, where the reaction of surface ocean plankton to temperature increase is still unclear.
Location: France
No related grants have been discovered for Thomas Schmidt.