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See detailAlterations of oral microbiota and impact on the gut microbiome in type 1 diabetes mellitus revealed by integrated multi-omic analyses
Kunath, Benoît UL; Hickl, Oskar UL; Teixeira Queiros, Pedro UL et al

in Microbiome (2022)

Background: Alterations to the gut microbiome have been linked to multiple chronic diseases. However, the drivers of such changes remain largely unknown. The oral cavity acts as a major route of exposure ... [more ▼]

Background: Alterations to the gut microbiome have been linked to multiple chronic diseases. However, the drivers of such changes remain largely unknown. The oral cavity acts as a major route of exposure to exogenous factors including pathogens, and processes therein may affect the communities in the subsequent compartments of the gastrointestinal tract. Here, we perform strain‑resolved, integrated meta‑genomic, transcriptomic, and proteomic analyses of paired saliva and stool samples collected from 35 individuals from eight families with multiple cases of type 1 diabetes mellitus (T1DM). Results: We identified distinct oral microbiota mostly reflecting competition between streptococcal species. More specifically, we found a decreased abundance of the commensal Streptococcus salivarius in the oral cavity of T1DM individuals, which is linked to its apparent competition with the pathobiont Streptococcus mutans. The decrease in S. salivarius in the oral cavity was also associated with its decrease in the gut as well as higher abundances in facultative anaerobes including Enterobacteria. In addition, we found evidence of gut inflammation in T1DM as reflected in the expression profiles of the Enterobacteria as well as in the human gut proteome. Finally, we were able to follow transmitted strain‑variants from the oral cavity to the gut at the individual omic levels, highlighting not only the transfer, but also the activity of the transmitted taxa along the gastrointestinal tract. Conclusions: Alterations of the oral microbiome in the context of T1DM impact the microbial communities in the lower gut, in particular through the reduction of “mouth‑to‑gut” transfer of Streptococcus salivarius. Our results indicate that the observed oral‑cavity‑driven gut microbiome changes may contribute towards the inflammatory processes involved in T1DM. Through the integration of multi‑omic analyses, we resolve strain‑variant “mouth‑to‑gut” transfer in a disease context. [less ▲]

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See detailExtensive transmission of microbes along the gastrointestinal tract
Schmidt, Thomas; Hayward, Matthew; Coelho, Luis et al

in eLife (2019)

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 ... [more ▼]

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 individuals from five countries, we found that transmission to, and subsequent colonization of, the large intestine by oral microbes is common and extensive among healthy individuals. 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. [less ▲]

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See detailSuperTarget and Matador: resources for exploring drug-target relationships
Guenther, Stefan; Kuhn, Michael; Dunkel, Mathias et al

in Nucleic Acids Research (2008), 36(SI), 919-922

The molecular basis of drug action is often not well understood. This is partly because the very abundant and diverse information generated in the past decades on drugs is hidden in millions of medical ... [more ▼]

The molecular basis of drug action is often not well understood. This is partly because the very abundant and diverse information generated in the past decades on drugs is hidden in millions of medical articles or textbooks. Therefore, we developed a one-stop data warehouse, SuperTarget that integrates drug-related information about medical indication areas, adverse drug effects, drug metabolization, pathways and Gene Ontology terms of the target proteins. An easy-to-use query interface enables the user to pose complex queries, for example to find drugs that target a certain pathway, interacting drugs that are metabolized by the same cytochrome P450 or drugs that target the same protein but are metabolized by different enzymes. Furthermore, we provide tools for 2D drug screening and sequence comparison of the targets. The database contains more than 2500 target proteins, which are annotated with about 7300 relations to 1500 drugs; the vast majority of entries have pointers to the respective literature source. A subset of these drugs has been annotated with additional binding information and indirect interactions and is available as a separate resource called Matador. SuperTarget and Matador are available at http://insilico.charite.de/supertarget and http://matador.embl.de. [less ▲]

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See detailShared components of protein complexes--versatile building blocks or biochemical artefacts?
von Mering, Christian; Bork, Peer; Dandekar, Thomas et al

in BioEssays (2004), 26(12), 1333-43

Protein complexes perform many important functions in the cell. Large-scale studies of protein-protein interactions have not only revealed new complexes but have also placed many proteins into multiple ... [more ▼]

Protein complexes perform many important functions in the cell. Large-scale studies of protein-protein interactions have not only revealed new complexes but have also placed many proteins into multiple complexes. Whilst the advocates of hypothesis-free research touted the discovery of these shared components as new links between diverse cellular processes, critical commentators denounced many of the findings as artefacts, thus questioning the usefulness of large-scale approaches. Here, we survey proteins known to be shared between complexes, as established in the literature, and compare them to shared components found in high-throughput screens. We discuss the various challenges to the identification and functional interpretation of bona fide shared components, namely contaminants, variant and megacomplexes, and transient interactions, and suggest that many of the novel shared components found in high-throughput screens are neither the results of contamination nor central components, but appear to be primarily regulatory links in cellular processes. [less ▲]

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See detailA comprehensive set of protein complexes in yeast: mining large scale protein-protein interaction screens.
Krause, Roland UL; von Mering, Christian; Bork, Peer

in Bioinformatics (2003), 19(15), 1901-8

MOTIVATION: The analysis of protein-protein interactions allows for detailed exploration of the cellular machinery. The biochemical purification of protein complexes followed by identification of ... [more ▼]

MOTIVATION: The analysis of protein-protein interactions allows for detailed exploration of the cellular machinery. The biochemical purification of protein complexes followed by identification of components by mass spectrometry is currently the method, which delivers the most reliable information--albeit that the data sets are still difficult to interpret. Consolidating individual experiments into protein complexes, especially for high-throughput screens, is complicated by many contaminants, the occurrence of proteins in otherwise dissimilar purifications due to functional re-use and technical limitations in the detection. A non-redundant collection of protein complexes from experimental data would be useful for biological interpretation, but manual assembly is tedious and often inconsistent. RESULTS: Here, we introduce a measure to define similarity within collections of purifications and generate a set of minimally redundant, comprehensive complexes using unsupervised clustering. AVAILABILITY: Programs and results are freely available from http://www.bork.embl-heidelberg.de/Docu/purclust/ [less ▲]

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See detailFunctional organization of the yeast proteome by systematic analysis of protein complexes.
Gavin, Anne-Claude; Bosche, Markus; Krause, Roland UL et al

in Nature (2002), 415(6868), 141-7

Most cellular processes are carried out by multiprotein complexes. The identification and analysis of their components provides insight into how the ensemble of expressed proteins (proteome) is organized ... [more ▼]

Most cellular processes are carried out by multiprotein complexes. The identification and analysis of their components provides insight into how the ensemble of expressed proteins (proteome) is organized into functional units. We used tandem-affinity purification (TAP) and mass spectrometry in a large-scale approach to characterize multiprotein complexes in Saccharomyces cerevisiae. We processed 1,739 genes, including 1,143 human orthologues of relevance to human biology, and purified 589 protein assemblies. Bioinformatic analysis of these assemblies defined 232 distinct multiprotein complexes and proposed new cellular roles for 344 proteins, including 231 proteins with no previous functional annotation. Comparison of yeast and human complexes showed that conservation across species extends from single proteins to their molecular environment. Our analysis provides an outline of the eukaryotic proteome as a network of protein complexes at a level of organization beyond binary interactions. This higher-order map contains fundamental biological information and offers the context for a more reasoned and informed approach to drug discovery. [less ▲]

Detailed reference viewed: 267 (8 UL)