669.
Deep ocean metagenomes provide insight into the metabolic architecture of bathypelagic microbial communities.
Acinas SG, Sánchez P, Salazar G, Cornejo-Castillo FM, Sebastián M, Logares R, Royo-Llonch M, Paoli L,
Sunagawa S, Hingamp P, Ogata H, Lima-Mendez G, Roux S, González JM, Arrieta JM, Alam IS, Kamau A, Bowler C,
Raes J, Pesant S,
Bork P, Agustí S, Gojobori T, Vaqué D, Sullivan MB, Pedrós-Alió C, Massana R, Duarte CM, Gasol JM
Abstract + PDF
The deep sea, the largest ocean's compartment, drives planetary-scale biogeochemical cycling. Yet, the functional exploration of its microbial communities lags far behind other environments. Here we analyze 58 metagenomes from tropical and subtropical deep oceans to generate the Malaspina Gene Database. Free-living or particle-attached lifestyles drive functional differences in bathypelagic prokaryotic communities, regardless of their biogeography. Ammonia and CO oxidation pathways are enriched in the free-living microbial communities and dissimilatory nitrate reduction to ammonium and H oxidation pathways in the particle-attached, while the Calvin Benson-Bassham cycle is the most prevalent inorganic carbon fixation pathway in both size fractions. Reconstruction of the Malaspina Deep Metagenome-Assembled Genomes reveals unique non-cyanobacterial diazotrophic bacteria and chemolithoautotrophic prokaryotes. The widespread potential to grow both autotrophically and heterotrophically suggests that mixotrophy is an ecologically relevant trait in the deep ocean. These results expand our understanding of the functional microbial structure and metabolic capabilities of the largest Earth aquatic ecosystem.
668.
Disease severity-specific neutrophil signatures in blood transcriptomes stratify COVID-19 patients.
Aschenbrenner AC, Mouktaroudi M, Krämer B, Oestreich M, Antonakos N, Nuesch-Germano M, Gkizeli K, Bonaguro L, Reusch N, Baßler K, Saridaki M, Knoll R, Pecht T, Kapellos TS, Doulou S, Kröger C, Herbert M, Holsten L, Horne A, Gemünd ID, Rovina N, Agrawal S, Dahm K, van Uelft M, Drews A, Lenkeit L, Bruse N, Gerretsen J, Gierlich J, Becker M, Händler K, Kraut M, Theis H, Mengiste S, De Domenico E, Schulte-Schrepping J, Seep L, Raabe J, Hoffmeister C, ToVinh M, Keitel V, Rieke G, Talevi V, Skowasch D, Aziz NA, Pickkers P, van de Veerdonk FL, Netea MG, Schultze JL, Kox M, Breteler MMB, Nattermann J, Koutsoukou A, Giamarellos-Bourboulis EJ, Ulas T, German COVID-19 Omics Initiative (DeCOI) , Altmüller J, Angelov A, Bals R, Bartholomäus A, Becker A, Bitzer M, Bonifacio E, Bork P, Casadei N, Clavel T, Colome-Tatche M, Diefenbach A, Dilthey A, Fischer N, Förstner K, Franzenburg S, Frick JS, Gabernet G, Gagneur J, Ganzenmüller T, Göpel S, Goesmann A, Hain T, Heimbach A, Hummel M, Iftner A, Iftner T, Janssen S, Kalinowski J, Kallies R, Kehr B, Keller A, Kim-Hellmuth S, Klein C, Kohlbacher O, Köhrer K, Korbel J, Kühnert D, Kurth I, Landthaler M, Li Y, Ludwig K, Makarewicz O, Marz M, McHardy A, Mertes C, Nöthen M, Nürnberg P, Ohler U, Ossowski S, Overmann J, Pfeffer K, Poetsch AR, Pühler A, Rajewsky N, Ralser M, Rieß O, Ripke S, Nunes da Rocha U, Rosenstiel P, Saliba AE, Sander LE, Sawitzki B, Schiffer P, Schneider W, Schulte EC, Schultze JL, Sczyrba A, Singh Y, Sonnabend M, Stegle O, Stoye J, Theis F, Vehreschild J, Vogel J, von Kleist M, Walker A, Walter J, Wieczorek D, Winkler S, Ziebuhr J
Abstract + PDF
The SARS-CoV-2 pandemic is currently leading to increasing numbers of COVID-19 patients all over the world. Clinical presentations range from asymptomatic, mild respiratory tract infection, to severe cases with acute respiratory distress syndrome, respiratory failure, and death. Reports on a dysregulated immune system in the severe cases call for a better characterization and understanding of the changes in the immune system.
667.
Metagenomic assessment of the global diversity and distribution of bacteria and fungi.
Abstract + PDF
Bacteria and fungi are of uttermost importance in determining environmental and host functioning. Despite close interactions between animals, plants, their associated microbiomes, and the environment they inhabit, the distribution and role of bacteria and especially fungi across host and environments as well as the cross-habitat determinants of their community compositions remain little investigated. Using a uniquely broad global dataset of 13 483 metagenomes, we analysed the microbiome structure and function of 25 host-associated and environmental habitats, focusing on potential interactions between bacteria and fungi. We found that the metagenomic relative abundance ratio of bacteria-to-fungi is a distinctive microbial feature of habitats. Compared with fungi, the cross-habitat distribution pattern of bacteria was more strongly driven by habitat type. Fungal diversity was depleted in host-associated communities compared with those in the environment, particularly terrestrial habitats, whereas this diversity pattern was less pronounced for bacteria. The relative gene functional potential of bacteria or fungi reflected their diversity patterns and appeared to depend on a balance between substrate availability and biotic interactions. Alongside helping to identify hotspots and sources of microbial diversity, our study provides support for differences in assembly patterns and processes between bacterial and fungal communities across different habitats.
666.
Protein Intake, Metabolic Status and the Gut Microbiota in Different Ethnicities: Results from Two Independent Cohorts.
Bel Lassen P, Attaye I, Adriouch S, Nicolaou M, Aron-Wisnewsky J, Nielsen T, Chakaroun R, Le Chatelier E,
Forslund S, Belda E,
Bork P, Bäckhed F, Stumvoll M, Pedersen O, Herrema H, Groen AK, Pinto-Sietsma SJ, Zwinderman AH, Nieuwdorp M, Clement K, On Behalf Of Metacardis Consortium
Abstract + PDF
Protein intake has been associated with the development of pre-diabetes (pre-T2D) and type 2 diabetes (T2D). The gut microbiota has the capacity to produce harmful metabolites derived from dietary protein. Furthermore, both the gut microbiota composition and metabolic status (e.g., insulin resistance) can be modulated by diet and ethnicity. However, to date most studies have predominantly focused on carbohydrate and fiber intake with regards to metabolic status and gut microbiota composition.
665.
The InterPro protein families and domains database: 20 years on.
Blum M, Chang HY, Chuguransky S, Grego T, Kandasaamy S, Mitchell A, Nuka G, Paysan-Lafosse T, Qureshi M, Raj S, Richardson L, Salazar GA, Williams L,
Bork P, Bridge A, Gough J, Haft DH,
Letunic I, Marchler-Bauer A, Mi H, Natale DA, Necci M, Orengo CA, Pandurangan AP, Rivoire C, Sigrist CJA, Sillitoe I, Thanki N, Thomas PD, Tosatto SCE, Wu CH, Bateman A, Finn RD
2021 Jan 8; 49(D1): D344-D354. PubMed:
33156333.Abstract + PDF
The InterPro database (https://www.ebi.ac.uk/interpro/) provides an integrative classification of protein sequences into families, and identifies functionally important domains and conserved sites. InterProScan is the underlying software that allows protein and nucleic acid sequences to be searched against InterPro's signatures. Signatures are predictive models which describe protein families, domains or sites, and are provided by multiple databases. InterPro combines signatures representing equivalent families, domains or sites, and provides additional information such as descriptions, literature references and Gene Ontology (GO) terms, to produce a comprehensive resource for protein classification. Founded in 1999, InterPro has become one of the most widely used resources for protein family annotation. Here, we report the status of InterPro (version 81.0) in its 20th year of operation, and its associated software, including updates to database content, the release of a new website and REST API, and performance improvements in InterProScan.
664.
Macroscale patterns of oceanic zooplankton composition and size structure.
Brandão MC, Benedetti F, Martini S, Soviadan YD, Irisson JO, Romagnan JB, Elineau A, Desnos C, Jalabert L, Freire AS, Picheral M, Guidi L, Gorsky G, Bowler C, Karp-Boss L, Henry N, De Vargas C, Sullivan MB, Tara Oceans Consortium Coordinators , Stemmann L, Lombard F, Acinas SG, Babin M,
Bork P, Boss E, Bowler C, Cochrane G, De Vargas C, Gorsky G, Guidi L, Grimsley N, Hingamp P, Iudicone D, Jaillon O,
Kandels S, Karp-Boss L, Karsenti E, Not F, Ogata H, Poulton N, Pesant S,
Raes J, Sardet C, Speich S, Stemmann L, Sullivan MB,
Sunagawa S, Wincker P
Abstract + PDF
Ocean plankton comprise organisms from viruses to fish larvae that are fundamental to ecosystem functioning and the provision of marine services such as fisheries and CO sequestration. The latter services are partly governed by variations in plankton community composition and the expression of traits such as body size at community-level. While community assembly has been thoroughly studied for the smaller end of the plankton size spectrum, the larger end comprises ectotherms that are often studied at the species, or group-level, rather than as communities. The body size of marine ectotherms decreases with temperature, but controls on community-level traits remain elusive, hindering the predictability of marine services provision. Here, we leverage Tara Oceans datasets to determine how zooplankton community composition and size structure varies with latitude, temperature and productivity-related covariates in the global surface ocean. Zooplankton abundance and median size decreased towards warmer and less productive environments, as a result of changes in copepod composition. However, some clades displayed the opposite relationships, which may be ascribed to alternative feeding strategies. Given that climate models predict increasingly warmed and stratified oceans, our findings suggest that zooplankton communities will shift towards smaller organisms which might weaken their contribution to the biological carbon pump.
663.
Author Correction: Macroscale patterns of oceanic zooplankton composition and size structure.
Brandão MC, Benedetti F, Martini S, Soviadan YD, Irisson JO, Romagnan JB, Elineau A, Desnos C, Jalabert L, Freire AS, Picheral M, Guidi L, Gorsky G, Bowler C, Karp-Boss L, Henry N, De Vargas C, Sullivan MB, Tara Oceans Consortium Coordinators , Stemmann L, Lombard F, Acinas SG, Babin M,
Bork P, Boss E, Bowler C, Cochrane G, De Vargas C, Gorsky G, Guidi L, Grimsley N, Hingamp P, Iudicone D, Jaillon O,
Kandels S, Karp-Boss L, Karsenti E, Not F, Ogata H, Poulton N, Pesant S,
Raes J, Sardet C, Speich S, Stemmann L, Sullivan MB,
Sunagawa S, Wincker P
PDF
662.
Human and preclinical studies of the host-gut microbiome co-metabolite hippurate as a marker and mediator of metabolic health.
Brial F, Chilloux J, Nielsen T, Vieira-Silva S, Falony G, Andrikopoulos P, Olanipekun M, Hoyles L, Djouadi F, Neves AL, Rodriguez-Martinez A, Mouawad GI, Pons N,
Forslund S, Le-Chatelier E, Le Lay A, Nicholson J, Hansen T, Hyötyläinen T, Clément K, Oresic M,
Bork P, Ehrlich SD,
Raes J, Pedersen OB, Gauguier D, Dumas ME
2021 Nov 11; 70(11): 2105-2114. PubMed:
33975870.Abstract + PDF
Gut microbial products are involved in regulation of host metabolism. In human and experimental studies, we explored the potential role of hippurate, a hepatic phase 2 conjugation product of microbial benzoate, as a marker and mediator of metabolic health.
661.
eggNOG-mapper v2: Functional Annotation, Orthology Assignments, and Domain Prediction at the Metagenomic Scale.
2021 Dec 9; 38(12): 5825-5829. PubMed:
34597405.Abstract + PDF
Even though automated functional annotation of genes represents a fundamental step in most genomic and metagenomic workflows, it remains challenging at large scales. Here, we describe a major upgrade to eggNOG-mapper, a tool for functional annotation based on precomputed orthology assignments, now optimized for vast (meta)genomic data sets. Improvements in version 2 include a full update of both the genomes and functional databases to those from eggNOG v5, as well as several efficiency enhancements and new features. Most notably, eggNOG-mapper v2 now allows for: (i) de novo gene prediction from raw contigs, (ii) built-in pairwise orthology prediction, (iii) fast protein domain discovery, and (iv) automated GFF decoration. eggNOG-mapper v2 is available as a standalone tool or as an online service at http://eggnog-mapper.embl.de.
660.
Combinatorial, additive and dose-dependent drug-microbiome associations.
Forslund SK, Chakaroun R,
Zimmermann-Kogadeeva M, Markó L, Aron-Wisnewsky J, Nielsen T,
Moitinho-Silva L,
Schmidt TSB, Falony G, Vieira-Silva S, Adriouch S,
Alves RJ, Assmann K, Bastard JP, Birkner T, Caesar R, Chilloux J,
Coelho LP, Fezeu L, Galleron N, Helft G, Isnard R, Ji B,
Kuhn M, Le Chatelier E, Myridakis A, Olsson L, Pons N, Prifti E, Quinquis B, Roume H, Salem JE, Sokolovska N, Tremaroli V, Valles-Colomer M, Lewinter C, Søndertoft NB, Pedersen HK, Hansen TH, MetaCardis Consortium , Gøtze JP, Køber L, Vestergaard H, Hansen T, Zucker JD, Hercberg S, Oppert JM,
Letunic I, Nielsen J, Bäckhed F, Ehrlich SD, Dumas ME,
Raes J, Pedersen O, Clément K, Stumvoll M,
Bork P 2021 Dec 8; 600(7889): 500-505. PubMed:
34880489.Abstract + PDF
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. Here, through integrated multi-omics analyses of 2,173 European residents from the MetaCardis cohort, we show that the explanatory power of drugs for the variability in both host and gut microbiome features exceeds that of disease. We quantify inferred effects of single medications, their combinations as well as additive effects, and show that the latter shift the metabolome and microbiome towards a healthier state, exemplified in synergistic reduction in serum atherogenic lipoproteins by statins combined with aspirin, or enrichment of intestinal Roseburia by diuretic agents combined with beta-blockers. Several antibiotics exhibit a quantitative relationship between the number of courses prescribed and progression towards a microbiome state that is associated with the severity of cardiometabolic disease. We also report a relationship between cardiometabolic drug dosage, improvement in clinical markers and microbiome composition, supporting direct drug effects. Taken together, our computational framework and resulting resources enable the disentanglement of the effects of drugs and disease on host and microbiome features in multimedicated individuals. Furthermore, the robust signatures identified using our framework provide new hypotheses for drug-host-microbiome interactions in cardiometabolic disease.
659.
Recurrent Frameshift Neoantigen Vaccine Elicits Protective Immunity With Reduced Tumor Burden and Improved Overall Survival in a Lynch Syndrome Mouse Model.
Gebert J, Gelincik O, Oezcan-Wahlbrink M, Marshall JD, Hernandez-Sanchez A, Urban K, Long M, Cortes E, Tosti E, Katzenmaier EM, Song Y, Elsaadi A, Deng N, Vilar E, Fuchs V, Nelius N,
Yuan YP, Ahadova A, Sei S, Shoemaker RH, Umar A, Wei L, Liu S,
Bork P, Edelmann W, von Knebel Doeberitz M, Lipkin SM, Kloor M
2021 Oct 2; 161(4): 1288-1302.e13. PubMed:
34224739.Abstract + PDF
DNA mismatch repair deficiency drives microsatellite instability (MSI). Cells with MSI accumulate numerous frameshift mutations. Frameshift mutations affecting cancer-related genes may promote tumorigenesis and, therefore, are shared among independently arising MSI tumors. Consequently, such recurrent frameshift mutations can give rise to shared immunogenic frameshift peptides (FSPs) that represent ideal candidates for a vaccine against MSI cancer. Pathogenic germline variants of mismatch repair genes cause Lynch syndrome (LS), a hereditary cancer syndrome affecting approximately 20-25 million individuals worldwide. Individuals with LS are at high risk of developing MSI cancer. Previously, we demonstrated safety and immunogenicity of an FSP-based vaccine in a phase I/IIa clinical trial in patients with a history of MSI colorectal cancer. However, the cancer-preventive effect of FSP vaccination in the scenario of LS has not yet been demonstrated.
658.
OGEE v3: Online GEne Essentiality database with increased coverage of organisms and human cell lines.
Gurumayum S, Jiang P, Hao X, Campos TL, Young ND, Korhonen PK, Gasser RB,
Bork P,
Zhao XM, He LJ,
Chen WH2021 Jan 8; 49(D1): D998-D1003. PubMed:
33084874.Abstract + PDF
OGEE is an Online GEne Essentiality database. Gene essentiality is not a static and binary property, rather a context-dependent and evolvable property in all forms of life. In OGEE we collect not only experimentally tested essential and non-essential genes, but also associated gene properties that contributes to gene essentiality. We tagged conditionally essential genes that show variable essentiality statuses across datasets to highlight complex interplays between gene functions and environmental/experimental perturbations. OGEE v3 contains gene essentiality datasets for 91 species; almost doubled from 48 species in previous version. To accommodate recent advances on human cancer essential genes (as known as tumor dependency genes) that could serve as targets for cancer treatment and/or drug development, we expanded the collection of human essential genes from 16 cell lines in previous to 581. These human cancer cell lines were tested with high-throughput experiments such as CRISPR-Cas9 and RNAi; in total, 150 of which were tested by both techniques. We also included factors known to contribute to gene essentiality for these cell lines, such as genomic mutation, methylation and gene expression, along with extensive graphical visualizations for ease of understanding of these factors. OGEE v3 can be accessible freely at https://v3.ogee.info.
657.
Dispersal strategies shape persistence and evolution of human gut bacteria.
2021 Jul 14; 29(7): 1167-1176.e9. PubMed:
34111423.Abstract + PDF
Human gut bacterial strains can co-exist with their hosts for decades, but little is known about how these microbes persist and disperse, and evolve thereby. Here, we examined these processes in 5,278 adult and infant fecal metagenomes, longitudinally sampled in individuals and families. Our analyses revealed that a subset of gut species is extremely persistent in individuals, families, and geographic regions, represented often by locally successful strains of the phylum Bacteroidota. These "tenacious" bacteria show high levels of genetic adaptation to the human host but a high probability of loss upon antibiotic interventions. By contrast, heredipersistent bacteria, notably Firmicutes, often rely on dispersal strategies with weak phylogeographic patterns but strong family transmissions, likely related to sporulation. These analyses describe how different dispersal strategies can lead to the long-term persistence of human gut microbes with implications for gut flora modulations.
656.
Bioaccumulation of therapeutic drugs by human gut bacteria.
Klünemann M, Andrejev S, Blasche S, Mateus A, Phapale P, Devendran S, Vappiani J, Simon B, Scott TA, Kafkia E, Konstantinidis D, Zirngibl K, Mastrorilli E, Banzhaf M, Mackmull MT, Hövelmann F, Nesme L, Brochado AR, Maier L, Bock T, Periwal V, Kumar M, Kim Y, Tramontano M, Schultz C, Beck M, Hennig J, Zimmermann M, Sévin DC, Cabreiro F, Savitski MM, Bork P, Typas A, Patil KR
2021 Sep 8; 597(7877): 533-538. PubMed:
34497420.Abstract + PDF
Bacteria in the gut can modulate the availability and efficacy of therapeutic drugs. However, the systematic mapping of the interactions between drugs and bacteria has only started recently and the main underlying mechanism proposed is the chemical transformation of drugs by microorganisms (biotransformation). Here we investigated the depletion of 15 structurally diverse drugs by 25 representative strains of gut bacteria. This revealed 70 bacteria-drug interactions, 29 of which had not to our knowledge been reported before. Over half of the new interactions can be ascribed to bioaccumulation; that is, bacteria storing the drug intracellularly without chemically modifying it, and in most cases without the growth of the bacteria being affected. As a case in point, we studied the molecular basis of bioaccumulation of the widely used antidepressant duloxetine by using click chemistry, thermal proteome profiling and metabolomics. We find that duloxetine binds to several metabolic enzymes and changes the metabolite secretion of the respective bacteria. When tested in a defined microbial community of accumulators and non-accumulators, duloxetine markedly altered the composition of the community through metabolic cross-feeding. We further validated our findings in an animal model, showing that bioaccumulating bacteria attenuate the behavioural response of Caenorhabditis elegans to duloxetine. Together, our results show that bioaccumulation by gut bacteria may be a common mechanism that alters drug availability and bacterial metabolism, with implications for microbiota composition, pharmacokinetics, side effects and drug responses, probably in an individual manner.
655.
Early IFN-α signatures and persistent dysfunction are distinguishing features of NK cells in severe COVID-19.
Krämer B, Knoll R, Bonaguro L, ToVinh M, Raabe J, Astaburuaga-García R, Schulte-Schrepping J, Kaiser KM, Rieke GJ, Bischoff J, Monin MB, Hoffmeister C, Schlabe S, De Domenico E, Reusch N, Händler K, Reynolds G, Blüthgen N, Hack G, Finnemann C, Nischalke HD, Strassburg CP, Stephenson E, Su Y, Gardner L, Yuan D, Chen D, Goldman J, Rosenstiel P, Schmidt SV, Latz E, Hrusovsky K, Ball AJ, Johnson JM, Koenig PA, Schmidt FI, Haniffa M, Heath JR, Kümmerer BM, Keitel V, Jensen B, Stubbemann P, Kurth F, Sander LE, Sawitzki B, Deutsche COVID-19 OMICS Initiative (DeCOI) , Altmüller J, Angelov A, Bals R, Bartholomäus A, Becker A, Bitzer M, Bonifacio E, Bork P, Casadei N, Clavel T, Colome-Tatche M, Diefenbach A, Dilthey A, Fischer N, Förstner K, Franzenburg S, Frick JS, Gabernet G, Gagneur J, Ganzenmüller T, Göpel S, Goesmann A, Hain T, Heimbach A, Hummel M, Iftner A, Iftner T, Janssen S, Kalinowski J, Kallies R, Kehr B, Keller A, Kim-Hellmuth S, Klein C, Kohlbacher O, Köhrer K, Korbel J, Kühnert D, Kurth I, Landthaler M, Li Y, Ludwig K, Makarewicz O, Marz M, McHardy A, Mertes C, Nöthen M, Nürnberg P, Ohler U, Ossowski S, Overmann J, Pfeffer K, Poetsch AR, Pühler A, Rajewsky N, Ralser M, Rieß O, Ripke S, Nunes da Rocha U, Rosenstiel P, Saliba AE, Sander LE, Sawitzki B, Schiffer P, Schneider W, Schulte EC, Schultze JL, Sczyrba A, Singh Y, Sonnabend M, Stegle O, Stoye J, Theis F, Vehreschild J, Vogel J, von Kleist M, Walker A, Walter J, Wieczorek D, Winkler S, Ziebuhr J, Aschenbrenner AC, Schultze JL, Nattermann J
2021 11 9; 54(11): 2650-2669.e14. PubMed:
34592166.Abstract + PDF
Longitudinal analyses of the innate immune system, including the earliest time points, are essential to understand the immunopathogenesis and clinical course of coronavirus disease (COVID-19). Here, we performed a detailed characterization of natural killer (NK) cells in 205 patients (403 samples; days 2 to 41 after symptom onset) from four independent cohorts using single-cell transcriptomics and proteomics together with functional studies. We found elevated interferon (IFN)-α plasma levels in early severe COVD-19 alongside increased NK cell expression of IFN-stimulated genes (ISGs) and genes involved in IFN-α signaling, while upregulation of tumor necrosis factor (TNF)-induced genes was observed in moderate diseases. NK cells exert anti-SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) activity but are functionally impaired in severe COVID-19. Further, NK cell dysfunction may be relevant for the development of fibrotic lung disease in severe COVID-19, as NK cells exhibited impaired anti-fibrotic activity. Our study indicates preferential IFN-α and TNF responses in severe and moderate COVID-19, respectively, and associates a prolonged IFN-α-induced NK cell response with poorer disease outcome.
654.
Interactive Tree Of Life (iTOL) v5: an online tool for phylogenetic tree display and annotation.
2021 Jul 2; 49(W1): W293-W296. PubMed:
33885785.Abstract + PDF
The Interactive Tree Of Life (https://itol.embl.de) is an online tool for the display, manipulation and annotation of phylogenetic and other trees. It is freely available and open to everyone. iTOL version 5 introduces a completely new tree display engine, together with numerous new features. For example, a new dataset type has been added (MEME motifs), while annotation options have been expanded for several existing ones. Node metadata display options have been extended and now also support non-numerical categorical values, as well as multiple values per node. Direct manual annotation is now available, providing a set of basic drawing and labeling tools, allowing users to draw shapes, labels and other features by hand directly onto the trees. Support for tree and dataset scales has been extended, providing fine control over line and label styles. Unrooted tree displays can now use the equal-daylight algorithm, proving a much greater display clarity. The user account system has been streamlined and expanded with new navigation options and currently handles >1 million trees from >70 000 individual users.
653.
SMART: recent updates, new developments and status in 2020.
2021 Jan 8; 49(D1): D458-D460. PubMed:
33104802.Abstract + PDF
SMART (Simple Modular Architecture Research Tool) is a web resource (https://smart.embl.de) for the identification and annotation of protein domains and the analysis of protein domain architectures. SMART version 9 contains manually curated models for more than 1300 protein domains, with a topical set of 68 new models added since our last update article (1). All the new models are for diverse recombinase families and subfamilies and as a set they provide a comprehensive overview of mobile element recombinases namely transposase, integrase, relaxase, resolvase, cas1 casposase and Xer like cellular recombinase. Further updates include the synchronization of the underlying protein databases with UniProt (2), Ensembl (3) and STRING (4), greatly increasing the total number of annotated domains and other protein features available in architecture analysis mode. Furthermore, SMART's vector-based protein display engine has been extended and updated to use the latest web technologies and the domain architecture analysis components have been optimized to handle the increased number of protein features available.
652.
Coupling proteomics and metabolomics for the unsupervised identification of protein-metabolite interactions in Chaetomium thermophilum.
Li YY,
Kuhn M, Zukowska-Kasprzyk J, Hennrich ML, Kastritis PL, O'Reilly FJ, Phapale P, Beck M, Gavin AC,
Bork P Abstract + PDF
Protein-metabolite interactions play an important role in the cell's metabolism and many methods have been developed to screen them in vitro. However, few methods can be applied at a large scale and not alter biological state. Here we describe a proteometabolomic approach, using chromatography to generate cell fractions which are then analyzed with mass spectrometry for both protein and metabolite identification. Integrating the proteomic and metabolomic analyses makes it possible to identify protein-bound metabolites. Applying the concept to the thermophilic fungus Chaetomium thermophilum, we predict 461 likely protein-metabolite interactions, most of them novel. As a proof of principle, we experimentally validate a predicted interaction between the ribosome and isopentenyl adenine.
651.
Polarization of microbial communities between competitive and cooperative metabolism.
Machado D,
Maistrenko OM, Andrejev S, Kim Y,
Bork P, Patil KR, Patil KR
Abstract + PDF
Resource competition and metabolic cross-feeding are among the main drivers of microbial community assembly. Yet the degree to which these two conflicting forces are reflected in the composition of natural communities has not been systematically investigated. Here, we use genome-scale metabolic modelling to assess the potential for resource competition and metabolic cooperation in large co-occurring groups (up to 40 members) across thousands of habitats. Our analysis reveals two distinct community types, which are clustered at opposite ends of a spectrum in a trade-off between competition and cooperation. At one end are highly cooperative communities, characterized by smaller genomes and multiple auxotrophies. At the other end are highly competitive communities, which feature larger genomes and overlapping nutritional requirements, and harbour more genes related to antimicrobial activity. The latter are mainly present in soils, whereas the former are found in both free-living and host-associated habitats. Community-scale flux simulations show that, whereas competitive communities can better resist species invasion but not nutrient shift, cooperative communities are susceptible to species invasion but resilient to nutrient change. We also show, by analysing an additional data set, that colonization by probiotic species is positively associated with the presence of cooperative species in the recipient microbiome. Together, our results highlight the bifurcation between competitive and cooperative metabolism in the assembly of natural communities and its implications for community modulation.
650.
Unravelling the collateral damage of antibiotics on gut bacteria.
Maier L, Goemans CV, Wirbel J,
Kuhn M, Eberl C, Pruteanu M, Müller P, Garcia-Santamarina S, Cacace E, Zhang B, Gekeler C, Banerjee T, Anderson EE, Milanese A, Löber U,
Forslund SK, Patil KR, Zimmermann M, Stecher B,
Zeller G,
Bork P, Typas A
2021 Nov 13; 599(7883): 120-124. PubMed:
34646011.Abstract + PDF
Antibiotics are used to fight pathogens but also target commensal bacteria, disturbing the composition of gut microbiota and causing dysbiosis and disease. Despite this well-known collateral damage, the activity spectrum of different antibiotic classes on gut bacteria remains poorly characterized. Here we characterize further 144 antibiotics from a previous screen of more than 1,000 drugs on 38 representative human gut microbiome species. Antibiotic classes exhibited distinct inhibition spectra, including generation dependence for quinolones and phylogeny independence for β-lactams. Macrolides and tetracyclines, both prototypic bacteriostatic protein synthesis inhibitors, inhibited nearly all commensals tested but also killed several species. Killed bacteria were more readily eliminated from in vitro communities than those inhibited. This species-specific killing activity challenges the long-standing distinction between bactericidal and bacteriostatic antibiotic classes and provides a possible explanation for the strong effect of macrolides on animal and human gut microbiomes. To mitigate this collateral damage of macrolides and tetracyclines, we screened for drugs that specifically antagonized the antibiotic activity against abundant Bacteroides species but not against relevant pathogens. Such antidotes selectively protected Bacteroides species from erythromycin treatment in human-stool-derived communities and gnotobiotic mice. These findings illluminate the activity spectra of antibiotics in commensal bacteria and suggest strategies to circumvent their adverse effects on the gut microbiota.
649.
Profiling cellular diversity in sponges informs animal cell type and nervous system evolution.
Musser JM, Schippers KJ, Nickel M, Mizzon G, Kohn AB, Pape C, Ronchi P, Papadopoulos N, Tarashansky AJ, Hammel JU, Wolf F, Liang C, Hernández-Plaza A, Cantalapiedra CP, Achim K, Schieber NL, Pan L, Ruperti F, Francis WR, Vargas S, Kling S, Renkert M, Polikarpov M, Bourenkov G, Feuda R, Gaspar I, Burkhardt P, Wang B,
Bork P, Beck M, Schneider TR, Kreshuk A, Wörheide G,
Huerta-Cepas J, Schwab Y, Moroz LL, Arendt D
2021 Nov 5; 374(6568): 717-723. PubMed:
34735222.Abstract + PDF
The evolutionary origin of metazoan cell types such as neurons and muscles is not known. Using whole-body single-cell RNA sequencing in a sponge, an animal without nervous system and musculature, we identified 18 distinct cell types. These include nitric oxide–sensitive contractile pinacocytes, amoeboid phagocytes, and secretory neuroid cells that reside in close contact with digestive choanocytes that express scaffolding and receptor proteins. Visualizing neuroid cells by correlative x-ray and electron microscopy revealed secretory vesicles and cellular projections enwrapping choanocyte microvilli and cilia. Our data show a communication system that is organized around sponge digestive chambers, using conserved modules that became incorporated into the pre- and postsynapse in the nervous systems of other animals.
648.
GUNC: detection of chimerism and contamination in prokaryotic genomes.
Abstract + PDF
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 individual 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.
647.
Prognostic performance of 7 biomarkers compared to liver biopsy in early alcohol-related liver disease.
Rasmussen DN, Thiele M, Johansen S, Kjærrgaard M, Lindvig KP, Israelsen M, Antonsen S, Detlefsen S, Krag A, GALAXY , MicrobLiver consortia , Anastasiadou E,
Arumugam M,
Bork P, Hansen T, Hartoft C, Israelsen H, Karsdal M, Legido-Quigley C, Melberg HO, Thiele M, Trebicka J, Krag A,
Bork P, Mann M, Matthijnssens J, Krag A, Hansen T
Abstract + PDF
Alcohol is the most common cause of liver-related mortality and morbidity. We therefore aimed to assess and compare the prognostic performance of elastography and blood-based markers to predict time to the first liver-related event, severe infection, and all-cause mortality in patients with a history of excess drinking.
646.
Compendium of 530 metagenome-assembled bacterial and archaeal genomes from the polar Arctic Ocean.
Royo-Llonch M, Sánchez P, Ruiz-González C, Salazar G, Pedrós-Alió C, Sebastián M, Labadie K, Paoli L, M Ibarbalz F, Zinger L, Churcheward B, Tara Oceans coordinators ,
Chaffron S, Eveillard D, Karsenti E,
Sunagawa S, Wincker P, Karp-Boss L, Bowler C, Acinas SG, Babin M,
Bork P, Boss E, Cochrane G, De Vargas C, Gorsky G, Grimsley N, Guidi L, Hingamp P, Iudicone D, Jaillon O,
Kandels S, Not F, Ogata H, Pesant S, Poulton N,
Raes J, Sardet C, Speich S, Setmmann L, Sullivan MB
Abstract + PDF
The role of the Arctic Ocean ecosystem in climate regulation may depend on the responses of marine microorganisms to environmental change. We applied genome-resolved metagenomics to 41 Arctic seawater samples, collected at various depths in different seasons during the Tara Oceans Polar Circle expedition, to evaluate the ecology, metabolic potential and activity of resident bacteria and archaea. We assembled 530 metagenome-assembled genomes (MAGs) to form the Arctic MAGs catalogue comprising 526 species. A total of 441 MAGs belonged to species that have not previously been reported and 299 genomes showed an exclusively polar distribution. Most Arctic MAGs have large genomes and the potential for fast generation times, both of which may enable adaptation to a copiotrophic lifestyle in nutrient-rich waters. We identified 38 habitat generalists and 111 specialists in the Arctic Ocean. We also found a general prevalence of 14 mixotrophs, while chemolithoautotrophs were mostly present in the mesopelagic layer during spring and autumn. We revealed 62 MAGs classified as key Arctic species, found only in the Arctic Ocean, showing the highest gene expression values and predicted to have habitat-specific traits. The Artic MAGs catalogue will inform our understanding of polar microorganisms that drive global biogeochemical cycles.
645.
A 12-genus bacterial signature identifies a group of severe autistic children with differential sensory behavior and brain structures.
Shi K, Zhang L, Yu J, Chen Z, Lai S, Zhao X, Li WG, Luo Q, Lin W, Feng J,
Bork P,
Zhao XM, Li F
PDF
644.
SARS-CoV-2 infection paralyzes cytotoxic and metabolic functions of the immune cells.
Singh Y, Trautwein C, Fendel R, Krickeberg N, Berezhnoy G, Bissinger R, Ossowski S, Salker MS, Casadei N, Riess O, Deutsche COVID-19 OMICS Initiate (DeCOI) , Altmüller J, Angelov A, Aschenbrenner AC, Bals R, Bartholomäus A, Becker A, Becker M, Bezdan D, Bitzer M, Blumert C, Bonifacio E,
Bork P, Boyke B, Blum H, Casadei N, Clavel T, Colome-Tatche M, Cornberg M, Velázquez IADLR, Diefenbach A, Dilthey A, Fischer N, Förstner K, Franzenburg S, Frick JS, Gabernet G, Gagneur J, Ganzenmueller T, Gauder M, Geißert J, Goesmann A, Göpel S, Grundhoff A, Grundmann H, Hain T, Hanses F, Hehr U, Heimbach A, Hoeper M, Horn F, Hübschmann D, Hummel M, Iftner T, Iftner A, Illig T, Janssen S, Kalinowski J, Kallies R, Kehr B, Keller A, Keppler OT, Kim-Hellmuth S, Klein C, Knop M, Kohlbacher O, Köhrer K,
Korbel JO, Kremsner PG, Kühnert D, Kurth I, Landthaler M, Li Y, Ludwig KU, Makarewicz O, Marz M, McHardy AC, Mertes C, Münchhoff M, Nahnsen S, Nöthen M, Ntoumi F, Nürnberg P, Ossowski S, Overmann J, Peter S, Pfeffer K, Pink I, Poetsch AR, Protzer U, Pühler A, Rajewsky N, Ralser M, Reiche K, Rieß O, Ripke S, da Rocha UN, Rosenstiel P, Saliba AE, Sander LE, Sawitzki B, Scheithauer S, Schiffer P, Schmid-Burgk J, Schneider W, Schulte EC, Schultze JL, Sczyrba A, Sharaf ML, Singh Y, Sonnabend M, Stegle O, Stoye J, Theis F, Ulas T, Vehreschild J, Velavan TP, Vogel J, Volland S, von Kleist M, Walker A, Walter J, Wieczorek D, Winkler S, Ziebuhr J.
Abstract + PDF
The SARS-CoV-2 virus is the causative agent of the global COVID-19 infectious disease outbreak, which can lead to acute respiratory distress syndrome (ARDS). However, it is still unclear how the virus interferes with immune cell and metabolic functions in the human body. In this study, we investigated the immune response in acute or convalescent COVID-19 patients. We characterized the peripheral blood mononuclear cells (PBMCs) using flow cytometry and found that CD8 T cells were significantly subsided in moderate COVID-19 and convalescent patients. Furthermore, characterization of CD8 T cells suggested that convalescent patients have significantly diminished expression of both perforin and granzyme A. Using H-NMR spectroscopy, we characterized the metabolic status of their autologous PBMCs. We found that fructose, lactate and taurine levels were elevated in infected (mild and moderate) patients compared with control and convalescent patients. Glucose, glutamate, formate and acetate levels were attenuated in COVID-19 (mild and moderate) patients. In summary, our report suggests that SARS-CoV-2 infection leads to disrupted CD8 T cytotoxic functions and changes the overall metabolic functions of immune cells.
643.
The STRING database in 2021: customizable protein-protein networks, and functional characterization of user-uploaded gene/measurement sets.
Szklarczyk D, Gable AL, Nastou KC, Lyon D, Kirsch R, Pyysalo S, Doncheva NT, Legeay M, Fang T,
Bork P,
Jensen LJ,
von Mering C 2021 Jan 8; 49(D1): D605-D612. PubMed:
33237311.Abstract + PDF
Cellular life depends on a complex web of functional associations between biomolecules. Among these associations, protein-protein interactions are particularly important due to their versatility, specificity and adaptability. The STRING database aims to integrate all known and predicted associations between proteins, including both physical interactions as well as functional associations. To achieve this, STRING collects and scores evidence from a number of sources: (i) automated text mining of the scientific literature, (ii) databases of interaction experiments and annotated complexes/pathways, (iii) computational interaction predictions from co-expression and from conserved genomic context and (iv) systematic transfers of interaction evidence from one organism to another. STRING aims for wide coverage; the upcoming version 11.5 of the resource will contain more than 14 000 organisms. In this update paper, we describe changes to the text-mining system, a new scoring-mode for physical interactions, as well as extensive user interface features for customizing, extending and sharing protein networks. In addition, we describe how to query STRING with genome-wide, experimental data, including the automated detection of enriched functionalities and potential biases in the user's query data. The STRING resource is available online, at https://string-db.org/.
642.
Correction to 'The STRING database in 2021: customizable protein-protein networks, and functional characterization of user-uploaded gene/measurement sets'.
Szklarczyk D, Gable AL, Nastou KC, Lyon D, Kirsch R, Pyysalo S, Doncheva NT, Legeay M, Fang T,
Bork P,
Jensen LJ,
von Mering C 2021 Oct 11; 49(18): 10800. PubMed:
34530444.PDF
641.
Progressive alcohol-related liver fibrosis is characterised by imbalanced collagen formation and degradation.
Thiele M, Johansen S, Gudmann NS, Madsen B, Kjaergaard M, Nielsen MJ, Leeming DJ, Jacobsen S, Bendtsen F, Møller S, Detlefsen S, Karsdal M, Krag A, GALAXY consortium ,
Arumugam M,
Bork P, Hansen T, Anastasiadou E, Hartoft C, Israelsen H, Legido-Quigley C, Melberg HO, Trebicka J
Abstract + PDF
Liver fibrosis accumulation is considered a turnover disease, with formation exceeding degradation, although this hypothesis has never been tested in humans.
640.
Utilizing the gut microbiome in decompensated cirrhosis and acute-on-chronic liver failure.
Abstract + PDF
The human gut microbiome has emerged as a major player in human health and disease. The liver, as the first organ to encounter microbial products that cross the gut epithelial barrier, is affected by the gut microbiome in many ways. Thus, the gut microbiome might play a major part in the development of liver diseases. The common end stage of liver disease is decompensated cirrhosis and the further development towards acute-on-chronic liver failure (ACLF). These conditions have high short-term mortality. There is evidence that translocation of components of the gut microbiota, facilitated by different pathogenic mechanisms such as increased gut epithelial permeability and portal hypertension, is an important driver of decompensation by induction of systemic inflammation, and thereby also ACLF. Elucidating the role of the gut microbiome in the aetiology of decompensated cirrhosis and ACLF deserves further investigation and improvement; and might be the basis for development of diagnostic and therapeutic strategies. In this Review, we focus on the possible pathogenic, diagnostic and therapeutic role of the gut microbiome in decompensation of cirrhosis and progression to ACLF.
639.
A Previously Undescribed Highly Prevalent Phage Identified in a Danish Enteric Virome Catalog.
Van Espen L, Bak EG, Beller L, Close L, Deboutte W, Juel HB, Nielsen T, Sinar D, De Coninck L, Frithioff-Bøjsøe C, Fonvig CE, Jacobsen S, Kjærgaard M, Thiele M,
Fullam A,
Kuhn M, Holm JC,
Bork P, Krag A, Hansen T,
Arumugam M, Matthijnssens J
2021 Oct 26; 6(5): e0038221. PubMed:
34665009.Abstract + PDF
Gut viruses are important, yet often neglected, players in the complex human gut microbial ecosystem. Recently, the number of human gut virome studies has been increasing; however, we are still only scratching the surface of the immense viral diversity. In this study, 254 virus-enriched fecal metagenomes from 204 Danish subjects were used to generate the anish nteric irme atalog (DEVoC) containing 12,986 nonredundant viral scaffolds, of which the majority was previously undescribed, encoding 190,029 viral genes. The DEVoC was used to compare 91 healthy DEVoC gut viromes from children, adolescents, and adults that were used to create the DEVoC. Gut viromes of healthy Danish subjects were dominated by phages. While most phage genomes (PGs) only occurred in a single subject, indicating large virome individuality, 39 PGs were present in more than 10 healthy subjects. Among these 39 PGs, the prevalences of three PGs were associated with age. To further study the prevalence of these 39 prevalent PGs, 1,880 gut virome data sets of 27 studies from across the world were screened, revealing several age-, geography-, and disease-related prevalence patterns. Two PGs also showed a remarkably high prevalence worldwide-a crAss-like phage (20.6% prevalence), belonging to the tentative subfamily, and a previously undescribed circular temperate phage infecting Bacteroides dorei (14.4% prevalence), called LoVEphage because it encodes ots f iral lements. Due to the LoVEphage's high prevalence and novelty, public data sets in which the LoVEphage was detected were assembled, resulting in an additional 18 circular LoVEphage-like genomes (67.9 to 72.4 kb). Through generation of the DEVoC, we added numerous previously uncharacterized viral genomes and genes to the ever-increasing worldwide pool of human gut viromes. The DEVoC, the largest human gut virome catalog generated from consistently processed fecal samples, facilitated the analysis of the 91 healthy Danish gut viromes. Characterizing the biggest cohort of healthy gut viromes from children, adolescents, and adults to date confirmed the previously established high interindividual variation in human gut viromes and demonstrated that the effect of age on the gut virome composition was limited to the prevalence of specific phage (groups). The identification of a previously undescribed prevalent phage illustrates the usefulness of developing virome catalogs, and we foresee that the DEVoC will benefit future analysis of the roles of gut viruses in human health and disease.
638.
Characterization of SARS-CoV-2 infection clusters based on integrated genomic surveillance, outbreak analysis and contact tracing in an urban setting.
Walker A, Houwaart T, Finzer P, Ehlkes L, Tyshaieva A, Damagnez M, Strelow D, Duplessis A, Nicolai J, Wienemann T, Tamayo T, Kohns Vasconcelos M, Hülse L, Hoffmann K, Lübke N, Hauka S, Andree M, Däumer MP, Thielen A, Kolbe-Busch S, Göbels K, Zotz R, Pfeffer K, Timm J, Dilthey AT, German COVID-19 Omics Initiative (DeCOI) , Altmüller J, Angelov A, Aschenbrenner AC, Bals R, Bartholomäus A, Becker A, Bezdan D, Bitzer M, Blum H, Bonifacio E,
Bork P, Casadei N, Clavel T, Colome-Tatche M, Velázquez IADLR, Diefenbach A, Dilthey A, Fischer N, Förstner K, Franzenburg S, Frick JS, Gabernet G, Gagneur J, Ganzenmüller T, Gauder M, Goesmann A, Göpel S, Grundhoff A, Grundmann H, Hain T, Heimbach A, Hummel M, Iftner T, Iftner A, Janssen S, Kalinowski J, Kallies R, Kehr B, Keller A, Keppler O, Kim-Hellmuth S, Klein C, Knop M, Kohlbacher O, Köhrer K,
Korbel JO, Kremsner PG, Kühnert D, Kurth I, Landthaler M, Li Y, Ludwig K, Makarewicz O, Marz M, McHardy A, Mertes C, Münchhoff M, Nahnsen S, Nöthen M, Ntoumi F, Nürnberg P, Ohler U, Ossowski S, Overmann J, Peter S, Pfeffer K, Poetsch AR, Protzer U, Pühler A, Rajewsky N, Ralser M, Rieß O, Ripke S, Rocha U, Rosenstiel P, Saliba E, Sander LE, Sawitzki B, Scheithauer S, Schiffer P, Schmid-Burgk J, Schneider W, Schulte EC, Schultze J, Sczyrba A, Sharaf ML, Singh Y, Sonnabend M, Stegle O, Stoye J, Theis F, Vehreschild J, Velavan TP, Vogel J, von Kleist M, Walker A, Walter J, Wieczorek D, Winkler S, Ziebuhr J.
2021 Jun 28; [Epub ahead of print] PubMed:
34181711.Abstract + PDF
Tracing of SARS-CoV-2 transmission chains is still a major challenge for public health authorities, when incidental contacts are not recalled or are not perceived as potential risk contacts. Viral sequencing can address key questions about SARS-CoV-2 evolution and may support reconstruction of viral transmission networks by integration of molecular epidemiology into classical contact tracing.
637.
Swarm Learning for decentralized and confidential clinical machine learning.
Warnat-Herresthal S, Schultze H, Shastry KL, Manamohan S, Mukherjee S, Garg V, Sarveswara R, Händler K, Pickkers P, Aziz NA, Ktena S, Tran F, Bitzer M, Ossowski S, Casadei N, Herr C, Petersheim D, Behrends U, Kern F, Fehlmann T, Schommers P, Lehmann C, Augustin M, Rybniker J, Altmüller J, Mishra N, Bernardes JP, Krämer B, Bonaguro L, Schulte-Schrepping J, De Domenico E, Siever C, Kraut M, Desai M, Monnet B, Saridaki M, Siegel CM, Drews A, Nuesch-Germano M, Theis H, Heyckendorf J, Schreiber S, Kim-Hellmuth S, COVID-19 Aachen Study (COVAS) , Nattermann J, Skowasch D, Kurth I, Keller A, Bals R, Nürnberg P, Rieß O, Rosenstiel P, Netea MG, Theis F, Mukherjee S, Backes M, Aschenbrenner AC, Ulas T, Deutsche COVID-19 OMICS Initiative (DeCOI) , Breteler MMB, Giamarellos-Bourboulis EJ, Kox M, Becker M, Cheran S, Woodacre MS, Goh EL, Schultze JL, Balfanz P, Eggermann T, Boor P, Hausmann R, Kuhn H, Isfort S, Stingl JC, Schmalzing G, Kuhl CK, Röhrig R, Marx G, Uhlig S, Dahl E, Müller-Wieland D, Dreher M, Marx N, Angelov A, Bartholomäus A, Becker A, Bezdan D, Blumert C, Bonifacio E, Bork P, Boyke B, Blum H, Clavel T, Colome-Tatche M, Cornberg M, Velázquez IADL, Diefenbach A, Dilthey A, Fischer N, Förstner K, Franzenburg S, Frick JS, Gabernet G, Gagneur J, Ganzenmueller T, Gauder M, Geißert J, Goesmann A, Göpel S, Grundhoff A, Grundmann H, Hain T, Hanses F, Hehr U, Heimbach A, Hoeper M, Horn F, Hübschmann D, Hummel M, Iftner T, Iftner A, Illig T, Janssen S, Kalinowski J, Kallies R, Kehr B, Keppler OT, Klein C, Knop M, Kohlbacher O, Köhrer K, Korbel J, Kremsner PG, Kühnert D, Landthaler M, Li Y, Ludwig KU, Makarewicz O, Marz M, McHardy AC, Mertes C, Münchhoff M, Nahnsen S, Nöthen M, Ntoumi F, Overmann J, Peter S, Pfeffer K, Pink I, Poetsch AR, Protzer U, Pühler A, Rajewsky N, Ralser M, Reiche K, Ripke S, da Rocha UN, Saliba AE, Sander LE, Sawitzki B, Scheithauer S, Schiffer P, Schmid-Burgk J, Schneider W, Schulte EC, Sczyrba A, Sharaf ML, Singh Y, Sonnabend M, Stegle O, Stoye J, Vehreschild J, Velavan TP, Vogel J, Volland S, von Kleist M, Walker A, Walter J, Wieczorek D, Winkler S, Ziebuhr J
2021 06; 594(7862): 265-270. PubMed:
34040261.Abstract + PDF
Fast and reliable detection of patients with severe and heterogeneous illnesses is a major goal of precision medicine. Patients with leukaemia can be identified using machine learning on the basis of their blood transcriptomes. However, there is an increasing divide between what is technically possible and what is allowed, because of privacy legislation. Here, to facilitate the integration of any medical data from any data owner worldwide without violating privacy laws, we introduce Swarm Learning-a decentralized machine-learning approach that unites edge computing, blockchain-based peer-to-peer networking and coordination while maintaining confidentiality without the need for a central coordinator, thereby going beyond federated learning. To illustrate the feasibility of using Swarm Learning to develop disease classifiers using distributed data, we chose four use cases of heterogeneous diseases (COVID-19, tuberculosis, leukaemia and lung pathologies). With more than 16,400 blood transcriptomes derived from 127 clinical studies with non-uniform distributions of cases and controls and substantial study biases, as well as more than 95,000 chest X-ray images, we show that Swarm Learning classifiers outperform those developed at individual sites. In addition, Swarm Learning completely fulfils local confidentiality regulations by design. We believe that this approach will notably accelerate the introduction of precision medicine.
636.
Microbiome meta-analysis and cross-disease comparison enabled by the SIAMCAT machine learning toolbox.
Abstract + PDF
The human microbiome is increasingly mined for diagnostic and therapeutic biomarkers using machine learning (ML). However, metagenomics-specific software is scarce, and overoptimistic evaluation and limited cross-study generalization are prevailing issues. To address these, we developed SIAMCAT, a versatile R toolbox for ML-based comparative metagenomics. We demonstrate its capabilities in a meta-analysis of fecal metagenomic studies (10,803 samples). When naively transferred across studies, ML models lost accuracy and disease specificity, which could however be resolved by a novel training set augmentation strategy. This reveals some biomarkers to be disease-specific, with others shared across multiple conditions. SIAMCAT is freely available from siamcat.embl.de .