| 1. |
- Vaga, S., et al.
(författare)
-
Compositional and functional differences of the mucosal microbiota along the intestine of healthy individuals
- 2020
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
-
Tidskriftsartikel (refereegranskat)abstract
- Gut mucosal microbes evolved closest to the host, developing specialized local communities. There is, however, insufficient knowledge of these communities as most studies have employed sequencing technologies to investigate faecal microbiota only. This work used shotgun metagenomics of mucosal biopsies to explore the microbial communities' compositions of terminal ileum and large intestine in 5 healthy individuals. Functional annotations and genome-scale metabolic modelling of selected species were then employed to identify local functional enrichments. While faecal metagenomics provided a good approximation of the average gut mucosal microbiome composition, mucosal biopsies allowed detecting the subtle variations of local microbial communities. Given their significant enrichment in the mucosal microbiota, we highlight the roles of Bacteroides species and describe the antimicrobial resistance biogeography along the intestine. We also detail which species, at which locations, are involved with the tryptophan/indole pathway, whose malfunctioning has been linked to pathologies including inflammatory bowel disease. Our study thus provides invaluable resources for investigating mechanisms connecting gut microbiota and host pathophysiology.
|
|
| 2. |
- Zrimec, Jan, 1981, et al.
(författare)
-
Deep learning suggests that gene expression is encoded in all parts of a co-evolving interacting gene regulatory structure
- 2020
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- Understanding the genetic regulatory code governing gene expression is an important challenge in molecular biology. However, how individual coding and non-coding regions of the gene regulatory structure interact and contribute to mRNA expression levels remains unclear. Here we apply deep learning on over 20,000 mRNA datasets to examine the genetic regulatory code controlling mRNA abundance in 7 model organisms ranging from bacteria to Human. In all organisms, we can predict mRNA abundance directly from DNA sequence, with up to 82% of the variation of transcript levels encoded in the gene regulatory structure. By searching for DNA regulatory motifs across the gene regulatory structure, we discover that motif interactions could explain the whole dynamic range of mRNA levels. Co-evolution across coding and non-coding regions suggests that it is not single motifs or regions, but the entire gene regulatory structure and specific combination of regulatory elements that define gene expression levels. Regulatory and coding regions of genes are shaped by evolution to control expression levels. Here, the authors use deep learning to identify rules controlling gene expression levels and suggest that all parts of the gene regulatory structure interact in this.
|
|
| 3. |
- Tiukova, Ievgeniia, 1987, et al.
(författare)
-
Chromosomal genome assembly of the ethanol production strain CBS 11270 indicates a highly dynamic genome structure in the yeast species Brettanomyces bruxellensis
- 2019
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203 .- 1932-6203. ; 14:5
-
Tidskriftsartikel (refereegranskat)abstract
- Here, we present the genome of the industrial ethanol production strain Brettanomyces bruxellensis CBS 11270. The nuclear genome was found to be diploid, containing four chromosomes with sizes of ranging from 2.2 to 4.0 Mbp. A 75 Kbp mitochondrial genome was also identified. Comparing the homologous chromosomes, we detected that 0.32% of nucleotides were polymorphic, i.e. formed single nucleotide polymorphisms (SNPs), 40.6% of them were found in coding regions (i.e. 0.13% of all nucleotides formed SNPs and were in coding regions). In addition, 8,538 indels were found. The total number of protein coding genes was 4897, of them, 4,284 were annotated on chromosomes; and the mitochondrial genome contained 18 protein coding genes. Additionally, 595 genes, which were annotated, were on contigs not associated with chromosomes. A number of genes was duplicated, most of them as tandem repeats, including a six-gene cluster located on chromosome 3. There were also examples of interchromosomal gene duplications, including a duplication of a six-gene cluster, which was found on both chromosomes 1 and 4. Gene copy number analysis suggested loss of heterozygosity for 372 genes. This may reflect adaptation to relatively harsh but constant conditions of continuous fermentation. Analysis of gene topology showed that most of these losses occurred in clusters of more than one gene, the largest cluster comprising 33 genes. Comparative analysis against the wine isolate CBS 2499 revealed 88,534 SNPs and 8,133 indels. Moreover, when the scaffolds of the CBS 2499 genome assembly were aligned against the chromosomes of CBS 11270, many of them aligned completely, some have chunks aligned to different chromosomes, and some were in fact rearranged. Our findings indicate a highly dynamic genome within the species B. bruxellensis and a tendency towards reduction of gene number in long-term continuous cultivation.
|
|
| 4. |
- Das, Promi, 1990, et al.
(författare)
-
In vitro co-cultures of human gut bacterial species as predicted from co-occurrence network analysis
- 2018
-
Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 13:3
-
Tidskriftsartikel (refereegranskat)abstract
- Network analysis of large metagenomic datasets generated by current sequencing technologies can reveal significant co-occurrence patterns between microbial species of a biological community. These patterns can be analyzed in terms of pairwise combinations between all species comprising a community. Here, we construct a co-occurrence network for abundant microbial species encompassing the three dominant phyla found in human gut. This was followed by an in vitro evaluation of the predicted microbe-microbe co-occurrences, where we chose species pairs Bifidobacterium adolescentis and Bacteroides thetaiotaomicron, as well as Faecalibacterium prausnitzii and Roseburia inulinivorans as model organisms for our study. We then delineate the outcome of the co-cultures when equal distributions of resources were provided. The growth behavior of the co-culture was found to be dependent on the types of microbial species present, their specific metabolic activities, and resulting changes in the culture environment. Through this reductionist approach and using novel in vitro combinations of microbial species under anaerobic conditions, the results of this work will aid in the understanding and design of synthetic community formulations.
|
|
| 5. |
- Begum, Neelu, et al.
(författare)
-
Integrative functional analysis uncovers metabolic differences between Candida species
- 2022
-
Ingår i: Communications Biology. - : Springer Nature. - 2399-3642. ; 5:1
-
Tidskriftsartikel (refereegranskat)abstract
- Metabolic differences between Candida species are uncovered using the BioFung database alongside genomic and metabolic analysis. Candida species are a dominant constituent of the human mycobiome and associated with the development of several diseases. Understanding the Candida species metabolism could provide key insights into their ability to cause pathogenesis. Here, we have developed the BioFung database, providing an efficient annotation of protein-encoding genes. Along, with BioFung, using carbohydrate-active enzyme (CAZymes) analysis, we have uncovered core and accessory features across Candida species demonstrating plasticity, adaption to the environment and acquired features. We show a greater importance of amino acid metabolism, as functional analysis revealed that all Candida species can employ amino acid metabolism. However, metabolomics revealed that only a specific cluster of species (AGAu species-C. albicans, C. glabrata and C. auris) utilised amino acid metabolism including arginine, cysteine, and methionine metabolism potentially improving their competitive fitness in pathogenesis. We further identified critical metabolic pathways in the AGAu cluster with biomarkers and anti-fungal target potential in the CAZyme profile, polyamine, choline and fatty acid biosynthesis pathways. This study, combining genomic analysis, and validation with gene expression and metabolomics, highlights the metabolic diversity with AGAu species that underlies their remarkable ability to dominate they mycobiome and cause disease.
|
|
| 6. |
- Feizi, Amir, 1980, et al.
(författare)
-
Human protein secretory pathway genes are expressed in a tissue-specific pattern to match processing demands of the secretome
- 2017
-
Ingår i: npj Systems Biology and Applications. - : Springer Science and Business Media LLC. - 2056-7189. ; 3:1
-
Tidskriftsartikel (refereegranskat)abstract
- Protein secretory pathway in eukaryal cells is responsible for delivering functional secretory proteins. The dysfunction of this pathway causes a range of important human diseases from congenital disorders to cancer. Despite the piled-up knowledge on the molecular biology and biochemistry level, the tissue-specific expression of the secretory pathway genes has not been analyzed on the transcriptome level. Based on the recent RNA-sequencing studies, the largest fraction of tissue-specific transcriptome encodes for the secretome (secretory proteins). Here, the question arises that if the expression levels of the secretory pathway genes have a tissue-specific tuning. In this study, we tackled this question by performing a meta-analysis of the recently published transcriptome data on human tissues. As a result, we detected 68 as called “extreme genes” which show an unusual expression pattern in specific gene families of the secretory pathway. We also inspected the potential functional link between detected extreme genes and the corresponding tissues enriched secretome. As a result, the detected extreme genes showed correlation with the enrichment of the nature and number of specific post-translational modifications in each tissue’s secretome. Our findings conciliate both the housekeeping and tissue-specific nature of the protein secretory pathway, which we attribute to a fine-tuned regulation of defined gene families to support the diversity of secreted proteins and their modifications.
|
|
| 7. |
- Yang, Hong, et al.
(författare)
-
A network-based approach reveals the dysregulated transcriptional regulation in non-alcoholic liver disease
- 2021
-
Ingår i: Iscience. - : Elsevier BV. - 2589-0042. ; 24:11
-
Tidskriftsartikel (refereegranskat)abstract
- Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease worldwide. We performed network analysis to investigate the dysregulated biological processes in the disease progression and revealed the molecular mechanism underlying NAFLD. Based on network analysis, we identified a highly conserved disease-associated gene module across three different NAFLD cohorts and highlighted the predominant role of key transcriptional regulators associated with lipid and cholesterol metabolism. In addition, we revealed the detailed metabolic differences between heterogeneous NAFLD patients through integrative systems analysis of transcriptomic data and liver-specific genomescale metabolic model. Furthermore, we identified transcription factors (TFs), including SREBF2, HNF4A, SREBF1, YY1, and KLF13, showing regulation of hepatic expression of genes in the NAFLD-associated modules and validated the TFs using data generated from a mouse NAFLD model. In conclusion, our integrative analysis facilitates the understanding of the regulatory mechanism of these perturbed TFs and their associated biological processes.
|
|
| 8. |
- Tiukova, Ievgeniia, 1987, et al.
(författare)
-
Assembly and analysis of the genome sequence of the yeast Brettanomyces naardenensis CBS 7540
- 2019
-
Ingår i: Microorganisms. - : MDPI AG. - 2076-2607. ; 7:11
-
Tidskriftsartikel (refereegranskat)abstract
- Brettanomyces naardenensis is a spoilage yeast with potential for biotechnological applications for production of innovative beverages with low alcohol content and high attenuation degree. Here, we present the first annotated genome of B. naardenensis CBS 7540. The genome of B. naardenensis CBS 7540 was assembled into 76 contigs, totaling 11,283,072 nucleotides. In total, 5168 protein-coding sequences were annotated. The study provides functional genome annotation, phylogenetic analysis, and discusses genetic determinants behind notable stress tolerance and biotechnological potential of B. naardenensis.
|
|
| 9. |
- Robinson, Jonathan, 1986, et al.
(författare)
-
An atlas of human metabolism
- 2020
-
Ingår i: Science Signaling. - : American Association for the Advancement of Science (AAAS). - 1945-0877 .- 1937-9145. ; 13:624
-
Tidskriftsartikel (refereegranskat)abstract
- Genome-scale metabolic models (GEMs) are valuable tools to study metabolism and provide a scaffold for the integrative analysis of omics data. Researchers have developed increasingly comprehensive human GEMs, but the disconnect among different model sources and versions impedes further progress. We therefore integrated and extensively curated the most recent human metabolic models to construct a consensus GEM, Human1. We demonstrated the versatility of Human1 through the generation and analysis of cell- and tissue-specific models using transcriptomic, proteomic, and kinetic data. We also present an accompanying web portal, Metabolic Atlas (https://www.metabolicatlas.org/), which facilitates further exploration and visualization of Human1 content. Human1 was created using a version-controlled, open-source model development framework to enable community-driven curation and refinement. This framework allows Human1 to be an evolving shared resource for future studies of human health and disease.
|
|
| 10. |
- Kampf, Caroline, et al.
(författare)
-
The human liver-specific proteome defined by transcriptomics and antibody-based profiling
- 2014
-
Ingår i: FASEB Journal. - : Wiley. - 1530-6860 .- 0892-6638. ; 28:7, s. 2901-2914
-
Tidskriftsartikel (refereegranskat)abstract
- Human liver physiology and the genetic etiology of the liver diseases can potentially be elucidated through the identification of proteins with enriched expression in the liver. Here, we combined data from RNA sequencing (RNA-Seq) and antibody-based immunohistochemistry across all major human tissues to explore the human liver proteome with enriched expression, as well as the cell type-enriched expression in hepatocyte and bile duct cells. We identified in total 477 protein-coding genes with elevated expression in the liver: 179 genes have higher expression as compared to all the other analyzed tissues; 164 genes have elevated transcript levels in the liver shared with at least one other tissue type; and an additional 134 genes have a mild level of increased expression in the liver. We identified the precise localization of these proteins through antibody-based protein profiling and the subcellular localization of these proteins through immunofluorescent-based profiling. We also identified the biological processes and metabolic functions associated with these proteins, investigated their contribution in the occurrence of liver diseases, and identified potential targets for their treatment. Our study demonstrates the use of RNA-Seq and antibody-based immunohistochemistry for characterizing the human liver proteome, as well as the use of tissue-specific proteins in identification of novel drug targets and discovery of biomarkers.
|
|
