Starkeya
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA606838 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| SRR11248247_subreads.fastq.gz | Fastqsanger.gz | |||
| SRR13020914_1.fastq.gz | Fastqsanger.gz | |||
| SRR13020914_2.fastq.gz | Fastqsanger.gz |
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Project description:Background: Ependymomas encompass multiple, clinically relevant tumor types based on localization and molecular profiles. Although tumors of the methylation class “spinal ependymoma” (SP-EPN) represent the most common intramedullary neoplasms in children and adults, their developmental origin is ill-defined, molecular data are scarce, and the potential heterogeneity within SP-EPN remains unexplored. The only known recurrent genetic events in SP-EPN are loss of chromosome 22q and NF2 mutations, but neither types and frequency of these alterations nor their clinical meaning have been described in a large, epigenetically defined series. Methods: We mapped SP-EPN transcriptomes (n=76) to developmental atlases of the developing and adult spinal cord to uncover potential developmental origins of these tumors. In addition, transcriptomic, epigenetic (n=234), genetic (n=140), and clinical analyses (n=115) were integrated for a detailed overview on this entity. Results: Integration of transcriptomic ependymoma data with single-cell atlases of the spinal cord identified mature adult ependymal cells to display highest similarities to SP-EPN. Unsupervised hierarchical clustering of tumor data together with integrated analysis of methylation profiles identified two molecular SP-EPN subtypes. Subtype 1 predominantly contained NF2 wild type sequences with regular NF2 expression but revealed more extensive copy number alterations. Subtype 2 harbored previously known germline or sporadic NF2 mutations and was NF2-deficient in most cases, more often showed multilocular disease, and demonstrated a significantly reduced progression-free survival. Conclusion: Based on integrated molecular profiling of a large tumor series we identify two distinct SP-EPN subtypes with important implications for genetic counseling, patient surveillance, and drug development priorities.
2024-01-26 | GSE242991 | GEO
Project description:Background: Ependymomas encompass multiple, clinically relevant tumor types based on localization and molecular profiles. Although tumors of the methylation class “spinal ependymoma” (SP-EPN) represent the most common intramedullary neoplasms in children and adults, their developmental origin is ill-defined, molecular data are scarce, and the potential heterogeneity within SP-EPN remains unexplored. The only known recurrent genetic events in SP-EPN are loss of chromosome 22q and NF2 mutations, but neither types and frequency of these alterations nor their clinical meaning have been described in a large, epigenetically defined series. Methods: We mapped SP-EPN transcriptomes (n=76) to developmental atlases of the developing and adult spinal cord to uncover potential developmental origins of these tumors. In addition, transcriptomic, epigenetic (n=234), genetic (n=140), and clinical analyses (n=115) were integrated for a detailed overview on this entity. Results: Integration of transcriptomic ependymoma data with single-cell atlases of the spinal cord identified mature adult ependymal cells to display highest similarities to SP-EPN. Unsupervised hierarchical clustering of tumor data together with integrated analysis of methylation profiles identified two molecular SP-EPN subtypes. Subtype 1 predominantly contained NF2 wild type sequences with regular NF2 expression but revealed more extensive copy number alterations. Subtype 2 harbored previously known germline or sporadic NF2 mutations and was NF2-deficient in most cases, more often showed multilocular disease, and demonstrated a significantly reduced progression-free survival. Conclusion: Based on integrated molecular profiling of a large tumor series we identify two distinct SP-EPN subtypes with important implications for genetic counseling, patient surveillance, and drug development priorities.
2024-01-26 | GSE242993 | GEO
Project description:Background: Ependymomas encompass multiple, clinically relevant tumor types based on localization and molecular profiles. Although tumors of the methylation class “spinal ependymoma” (SP-EPN) represent the most common intramedullary neoplasms in children and adults, their developmental origin is ill-defined, molecular data are scarce, and the potential heterogeneity within SP-EPN remains unexplored. The only known recurrent genetic events in SP-EPN are loss of chromosome 22q and NF2 mutations, but neither types and frequency of these alterations nor their clinical meaning have been described in a large, epigenetically defined series. Methods: We mapped SP-EPN transcriptomes (n=76) to developmental atlases of the developing and adult spinal cord to uncover potential developmental origins of these tumors. In addition, transcriptomic, epigenetic (n=234), genetic (n=140), and clinical analyses (n=115) were integrated for a detailed overview on this entity. Results: Integration of transcriptomic ependymoma data with single-cell atlases of the spinal cord identified mature adult ependymal cells to display highest similarities to SP-EPN. Unsupervised hierarchical clustering of tumor data together with integrated analysis of methylation profiles identified two molecular SP-EPN subtypes. Subtype 1 predominantly contained NF2 wild type sequences with regular NF2 expression but revealed more extensive copy number alterations. Subtype 2 harbored previously known germline or sporadic NF2 mutations and was NF2-deficient in most cases, more often showed multilocular disease, and demonstrated a significantly reduced progression-free survival. Conclusion: Based on integrated molecular profiling of a large tumor series we identify two distinct SP-EPN subtypes with important implications for genetic counseling, patient surveillance, and drug development priorities.
2024-01-26 | GSE242992 | GEO
Project description:Unlabelled1,2-Dichloroethane (DCA) is a problematic xenobiotic groundwater pollutant. Bacteria are capable of biodegrading DCA, but the evolution of such bacteria is not well understood. In particular, the mechanisms by which bacteria acquire the key dehalogenase genes dhlA and dhlB have not been well defined. In this study, the genomic context of dhlA and dhlB was determined in three aerobic DCA-degrading bacteria (Starkeya novella strain EL1, Xanthobacter autotrophicus strain EL4, and Xanthobacter flavus strain EL8) isolated from a groundwater treatment plant (GTP). A haloalkane dehalogenase gene (dhlA) identical to the canonical dhlA gene from Xanthobacter sp. strain GJ10 was present in all three isolates, and, in each case, the dhlA gene was carried on a variant of a 37-kb circular plasmid, which was named pDCA. Sequence analysis of the repA replication initiator gene indicated that pDCA was a member of the pTAR plasmid family, related to catabolic plasmids from the Alphaproteobacteria, which enable growth on aromatics, dimethylformamide, and tartrate. Genes for plasmid replication, mobilization, and stabilization were identified, along with two insertion sequences (ISXa1 and ISPme1) which were likely to have mobilized dhlA and dhlB and played a role in the evolution of aerobic DCA-degrading bacteria. Two haloacid dehalogenase genes (dhlB1 and dhlB2) were detected in the GTP isolates; dhlB1 was most likely chromosomal and was similar to the canonical dhlB gene from strain GJ10, while dhlB2 was carried on pDCA and was not closely related to dhlB1 Heterologous expression of the DhlB2 protein confirmed that this plasmid-borne dehalogenase was capable of chloroacetate dechlorination.ImportanceEarlier studies on the DCA-degrading Xanthobacter sp. strain GJ10 indicated that the key dehalogenases dhlA and dhlB were carried on a 225-kb linear plasmid and on the chromosome, respectively. The present study has found a dramatically different gene organization in more recently isolated DCA-degrading Xanthobacter strains from Australia, in which a relatively small circular plasmid (pDCA) carries both dhlA and dhlB homologs. pDCA represents a true organochlorine-catabolic plasmid, first because its only obvious metabolic phenotype is dehalogenation of organochlorines, and second because acquisition of this plasmid provides both key enzymes required for carbon-chlorine bond cleavage. The discovery of the alternative haloacid dehalogenase dhlB2 in pDCA increases the known genetic diversity of bacterial chloroacetate-hydrolyzing enzymes.
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Project description:The highly diverse and metabolically versatile microbial communities found in soil environments are major contributors to the global carbon, nitrogen, and sulfur cycles. We have used a combination of genome -based pathway analysis with proteomics and gene expression studies to investigate metabolic adaptation in a representative of these bacteria, Starkeya novella, which was originally isolated from agricultural soil. This bacterium was the first facultative sulfur chemolithoautotroph that was isolated and it is also able to grow with methanol and on over 39 substrates as a heterotroph. However, using glucose, fructose, methanol, thiosulfate as well as combinations of the carbon compounds with thiosulfate as growth substrates we have demonstrated here that contrary to the previous classification, S. novella is not a facultative sulfur chemolitho- and methylotroph, as the enzyme systems required for these two growth modes are always expressed at high levels. This is typical for key metabolic pathways. In addition enzymes for various pathways of carbon dioxide fixation were always expressed at high levels, even during heterotrophic growth on glucose or fructose, which suggests a role for these pathways beyond the generation of reduced carbon units for cell growth, possibly in redox balancing of metabolism. Our results then indicate that S. novella, a representative of the Xanthobacteraceae family of methylotrophic soil and freshwater dwelling bacteria, employs a mixotrophic growth strategy under all conditions tested here. As a result the contribution of this bacterium to either carbon sequestration or the release of climate active substances could vary very quickly, which has direct implications for the modeling of such processes if mixotrophy proves to be the main growth strategy for large populations of soil bacteria.
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