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Rat gut extrachromosomal elements for the Critical Assessment of Metagenomic Interpretation (CAMI)

ABSTRACT: Rat gut extrachromosomal elements for the Critical Assessment of Metagenomic Interpretation (CAMI)

PROVIDER: PRJEB20380 | ENA |

REPOSITORIES: ENA

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			Action	DRS
		Other
		Other
	ERR1924580.fastq.gz	Fastqsanger.gz
	ERR1924580_1.fastq.gz	Fastqsanger.gz
	ERR1924580_2.fastq.gz	Fastqsanger.gz

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Critical Assessment of MetaProteome Investigation 2 (CAMPI-2)

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Extrachromosomal DNA-driven oncogene dosage heterogeneity promotes rapid adaptation to therapy in MYCN-amplified cancers

Project description:Extrachromosomal DNA (ecDNA) amplification enhances intercellular oncogene dosage variability and accelerates tumor evolution by violating foundational principles of genetic inheritance through its asymmetric mitotic segregation. Spotlighting high-risk neuroblastoma we demonstrate how ecDNA amplification undermines the clinical efficacy of current therapies in cancers with extrachromosomal MYCN amplification. Integrating theoretical models of oncogene copy number-dependent fitness with single-cell ecDNA quantification and phenotype analyses, we reveal that ecDNA copy number heterogeneity drives phenotypic diversity and determines treatment sensitivity through mechanisms unattainable by chromosomal oncogene amplification. We demonstrate that ecDNA copy number directly influences critical cell fate decisions in cancer cell lines, patient-derived xenografts and primary neuroblastomas, illustrating how extrachromosomal oncogene dosage-driven phenotypic diversity offers a strong evolutionary advantage under therapeutic pressure. Furthermore, we identify senescent ecDNA-containing cells with reduced copy numbers in neuroblastomas and other MYC-amplified cancers as a source of treatment resistance and outline a strategy for their targeted elimination to improve the poor outcome of patients with MYCN-amplified cancers.

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Long-read metagenomic exploration of extrachromosomal mobile genetic elements in the human gut.

Project description:BackgroundElucidating the ecological and biological identity of extrachromosomal mobile genetic elements (eMGEs), such as plasmids and bacteriophages, in the human gut remains challenging due to their high complexity and diversity.ResultsHere, we show efficient identification of eMGEs as complete circular or linear contigs from PacBio long-read metagenomic data. De novo assembly of PacBio long reads from 12 faecal samples generated 82 eMGE contigs (2.5~666.7-kb), which were classified as 71 plasmids and 11 bacteriophages, including 58 novel plasmids and six bacteriophages, and complete genomes of five diverse crAssphages with terminal direct repeats. In a dataset of 413 gut metagenomes from five countries, many of the identified plasmids were highly abundant and prevalent. The ratio of gut plasmids by our plasmid data is more than twice that in the public database. Plasmids outnumbered bacterial chromosomes three to one on average in this metagenomic dataset. Host prediction suggested that Bacteroidetes-associated plasmids predominated, regardless of microbial abundance. The analysis found several plasmid-enriched functions, such as inorganic ion transport, while antibiotic resistance genes were harboured mostly in low-abundance Proteobacteria-associated plasmids.ConclusionsOverall, long-read metagenomics provided an efficient approach for unravelling the complete structure of human gut eMGEs, particularly plasmids.

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