| 1. |
- Altenhoff, Adrian M., et al.
(författare)
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Standardized benchmarking in the quest for orthologs
- 2016
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Ingår i: Nature Methods. - 1548-7091 .- 1548-7105. ; 13:5, s. 425-
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Tidskriftsartikel (refereegranskat)abstract
- Achieving high accuracy in orthology inference is essential for many comparative, evolutionary and functional genomic analyses, yet the true evolutionary history of genes is generally unknown and orthologs are used for very different applications across phyla, requiring different precision-recall trade-offs. As a result, it is difficult to assess the performance of orthology inference methods. Here, we present a community effort to establish standards and an automated web-based service to facilitate orthology benchmarking. Using this service, we characterize 15 well-established inference methods and resources on a battery of 20 different benchmarks. Standardized benchmarking provides a way for users to identify the most effective methods for the problem at hand, sets a minimum requirement for new tools and resources, and guides the development of more accurate orthology inference methods.
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| 2. |
- Andrikopoulos, Petros, et al.
(författare)
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Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide
- 2023
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Ingår i: Nature Communications. - 2041-1723 .- 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- The host-microbiota co-metabolite trimethylamine N-oxide (TMAO) is linked to increased cardiovascular risk but how its circulating levels are regulated remains unclear. We applied "explainable" machine learning, univariate, multivariate and mediation analyses of fasting plasma TMAO concentration and a multitude of phenotypes in 1,741 adult Europeans of the MetaCardis study. Here we show that next to age, kidney function is the primary variable predicting circulating TMAO, with microbiota composition and diet playing minor, albeit significant, roles. Mediation analysis suggests a causal relationship between TMAO and kidney function that we corroborate in preclinical models where TMAO exposure increases kidney scarring. Consistent with our findings, patients receiving glucose-lowering drugs with reno-protective properties have significantly lower circulating TMAO when compared to propensity-score matched control individuals. Our analyses uncover a bidirectional relationship between kidney function and TMAO that can potentially be modified by reno-protective anti-diabetic drugs and suggest a clinically actionable intervention for decreasing TMAO-associated excess cardiovascular risk.
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| 3. |
- Bahram, Mohammad, et al.
(författare)
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Newly designed 16S rRNA metabarcoding primers amplify diverse and novel archaeal taxa from the environment
- 2019
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Ingår i: Environmental Microbiology Reports. - : WILEY. - 1758-2229 .- 1758-2229. ; 11:4, s. 487-494
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Tidskriftsartikel (refereegranskat)abstract
- High-throughput studies of microbial communities suggest that Archaea are a widespread component of microbial diversity in various ecosystems. However, proper quantification of archaeal diversity and community ecology remains limited, as sequence coverage of Archaea is usually low owing to the inability of available prokaryotic primers to efficiently amplify archaeal compared to bacterial rRNA genes. To improve identification and quantification of Archaea, we designed and validated the utility of several primer pairs to efficiently amplify archaeal 16S rRNA genes based on up-to-date reference genes. We demonstrate that several of these primer pairs amplify phylogenetically diverse Archaea with high sequencing coverage, outperforming commonly used primers. Based on comparing the resulting long 16S rRNA gene fragments with public databases from all habitats, we found several novel family- to phylum-level archaeal taxa from topsoil and surface water. Our results suggest that archaeal diversity has been largely overlooked due to the limitations of available primers, and that improved primer pairs enable to estimate archaeal diversity more accurately.
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| 4. |
- Bowers, Robert M., et al.
(författare)
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Minimum information about a single amplified genome (MISAG) and a metagenome-assembled genome (MIMAG) of bacteria and archaea
- 2017
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Ingår i: Nature Biotechnology. - : NATURE PUBLISHING GROUP. - 1087-0156 .- 1546-1696. ; 35:8, s. 725-731
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Tidskriftsartikel (refereegranskat)abstract
- We present two standards developed by the Genomic Standards Consortium (GSC) for reporting bacterial and archaeal genome sequences. Both are extensions of the Minimum Information about Any (x) Sequence (MIxS). The standards are the Minimum Information about a Single Amplified Genome (MISAG) and the Minimum Information about a Metagenome-Assembled Genome (MIMAG), including, but not limited to, assembly quality, and estimates of genome completeness and contamination. These standards can be used in combination with other GSC checklists, including the Minimum Information about a Genome Sequence (MIGS), Minimum Information about a Metagenomic Sequence (MIMS), and Minimum Information about a Marker Gene Sequence (MIMARKS). Community-wide adoption of MISAG and MIMAG will facilitate more robust comparative genomic analyses of bacterial and archaeal diversity.
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| 5. |
- Brial, François, et al.
(författare)
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Human and preclinical studies of the host-gut microbiome co-metabolite hippurate as a marker and mediator of metabolic health
- 2021
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Ingår i: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 70:11, s. 2105-2114
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: 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.DESIGN: In 271 middle-aged non-diabetic Danish individuals, who were stratified on habitual dietary intake, we applied 1H-nuclear magnetic resonance (NMR) spectroscopy of urine samples and shotgun-sequencing-based metagenomics of the gut microbiome to explore links between the urine level of hippurate, measures of the gut microbiome, dietary fat and markers of metabolic health. In mechanistic experiments with chronic subcutaneous infusion of hippurate to high-fat-diet-fed obese mice, we tested for causality between hippurate and metabolic phenotypes.RESULTS: In the human study, we showed that urine hippurate positively associates with microbial gene richness and functional modules for microbial benzoate biosynthetic pathways, one of which is less prevalent in the Bacteroides 2 enterotype compared with Ruminococcaceae or Prevotella enterotypes. Through dietary stratification, we identify a subset of study participants consuming a diet rich in saturated fat in which urine hippurate concentration, independently of gene richness, accounts for links with metabolic health. In the high-fat-fed mice experiments, we demonstrate causality through chronic infusion of hippurate (20 nmol/day) resulting in improved glucose tolerance and enhanced insulin secretion.CONCLUSION: Our human and experimental studies show that a high urine hippurate concentration is a general marker of metabolic health, and in the context of obesity induced by high-fat diets, hippurate contributes to metabolic improvements, highlighting its potential as a mediator of metabolic health.
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| 6. |
- Forslund, Sofia K., et al.
(författare)
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Combinatorial, additive and dose-dependent drug–microbiome associations
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 600:7889, s. 500-505
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Tidskriftsartikel (refereegranskat)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 discovery1–5. 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.
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| 7. |
- Gossmann, Toni I., et al.
(författare)
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Ice-Age Climate Adaptations Trap the Alpine Marmot in a State of Low Genetic Diversity
- 2019
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Ingår i: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 29:10, s. 1712-1720.e7
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Tidskriftsartikel (refereegranskat)abstract
- © 2019 The Author(s) Some species responded successfully to prehistoric changes in climate [1, 2], while others failed to adapt and became extinct [3]. The factors that determine successful climate adaptation remain poorly understood. We constructed a reference genome and studied physiological adaptations in the Alpine marmot (Marmota marmota), a large ground-dwelling squirrel exquisitely adapted to the “ice-age” climate of the Pleistocene steppe [4, 5]. Since the disappearance of this habitat, the rodent persists in large numbers in the high-altitude Alpine meadow [6, 7]. Genome and metabolome showed evidence of adaptation consistent with cold climate, affecting white adipose tissue. Conversely, however, we found that the Alpine marmot has levels of genetic variation that are among the lowest for mammals, such that deleterious mutations are less effectively purged. Our data rule out typical explanations for low diversity, such as high levels of consanguineous mating, or a very recent bottleneck. Instead, ancient demographic reconstruction revealed that genetic diversity was lost during the climate shifts of the Pleistocene and has not recovered, despite the current high population size. We attribute this slow recovery to the marmot's adaptive life history. The case of the Alpine marmot reveals a complicated relationship between climatic changes, genetic diversity, and conservation status. It shows that species of extremely low genetic diversity can be very successful and persist over thousands of years, but also that climate-adapted life history can trap a species in a persistent state of low genetic diversity. Despite being highly abundant and well adapted, Gossmann et al. report that the Alpine marmot is among the least genetically diverse animal species. The low diversity is found to be the consequence of consecutive, climate-related events, including long-term extreme niche adaptation, that also greatly retarded the recovery of its genetic diversity.
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| 8. |
- Hillier, Ladeana W, et al.
(författare)
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Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution
- 2004
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 432:7018, s. 695-716
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Tidskriftsartikel (refereegranskat)abstract
- We present here a draft genome sequence of the red jungle fowl, Gallus gallus. Because the chicken is a modern descendant of the dinosaurs and the first non-mammalian amniote to have its genome sequenced, the draft sequence of its genome--composed of approximately one billion base pairs of sequence and an estimated 20,000-23,000 genes--provides a new perspective on vertebrate genome evolution, while also improving the annotation of mammalian genomes. For example, the evolutionary distance between chicken and human provides high specificity in detecting functional elements, both non-coding and coding. Notably, many conserved non-coding sequences are far from genes and cannot be assigned to defined functional classes. In coding regions the evolutionary dynamics of protein domains and orthologous groups illustrate processes that distinguish the lineages leading to birds and mammals. The distinctive properties of avian microchromosomes, together with the inferred patterns of conserved synteny, provide additional insights into vertebrate chromosome architecture.
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| 9. |
- Juncker, Agnieszka S, et al.
(författare)
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Sequence-based feature prediction and annotation of proteins
- 2009
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1465-6914 .- 1465-6906. ; 10:2, s. 206-
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Tidskriftsartikel (refereegranskat)abstract
- A recent trend in computational methods for annotation of protein function is that many prediction tools are combined in complex workflows and pipelines to facilitate the analysis of feature combinations, for example, the entire repertoire of kinase-binding motifs in the human proteome.
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| 10. |
- Kleinteich, Julia, et al.
(författare)
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Pole-to-Pole Connections : Similarities between Arctic and Antarctic Microbiomes and Their Vulnerability to Environmental Change
- 2017
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Ingår i: Frontiers in Ecology and Evolution. - : FRONTIERS MEDIA SA. - 2296-701X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- The global biogeography of microorganisms remains poorly resolved, which limits the current understanding of microbial resilience toward environmental changes. Using high-throughput 16S rRNA gene amplicon sequencing, we characterized the microbial diversity of terrestrial and lacustrine biofilms from the Arctic, Antarctic and temperate regions. Our analyses suggest that bacterial community compositions at the poles are more similar to each other than they are to geographically closer temperate habitats, with 32% of all operational taxonomic units (OTUs) co-occurring in both polar regions. While specific microbial taxa were confined to distinct regions, representing potentially endemic populations, the percentage of cosmopolitan taxa was higher in Arctic (43%) than in Antarctic samples (36%). The overlap in polar microbial OTUs may be explained by natural or anthropogenically-mediated dispersal in combination with environmental filtering. Current and future changing environmental conditions may enhance microbial invasion, establishment of cosmopolitan genotypes and loss of endemic taxa.
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