Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Co-mapping Clonal and Transcriptional Heterogeneity in Somatic Evolution via GoT-Multi.

ABSTRACT: Somatic evolution leads to clonal heterogeneity, which fuels cancer progression and therapy resistance. To decipher the consequences of clonal heterogeneity, we require a method that deconvolutes complex clonal architectures and their downstream transcriptional states. We developed Genotyping of Transcriptomes for multiple targets and sample types (GoT-Multi), a high-throughput, formalin-fixed paraffin-embedded (FFPE) tissue-compatible single-cell multi-omics for co-detection of multiple somatic genotypes and whole transcriptomes. We developed an ensemble-based machine learning pipeline to optimize genotyping. We applied GoT-Multi to frozen or FFPE samples of Richter transformation, a progression of chronic lymphocytic leukemia to therapy-resistant large B cell lymphoma. GoT-Multi detected heterogeneous cancer cell states with genotypic data of 27 mutations, enabling clonal architecture reconstruction linked with their transcriptional programs. Distinct subclonal genotypes, including therapy-resistant mutations, converged on an inflammatory state. Other subclones displayed enhanced proliferation and/or MYC program. Thus, GoT-Multi revealed that distinct genotypic identities may converge on similar transcriptional states to mediate therapy resistance.

ORGANISM(S): Homo sapiens

PROVIDER: GSE294045 | GEO | 2025/09/03

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

CaClust: linking genotype to transcriptional heterogeneity of follicular lymphoma using BCR and exomic variants (K5B)

Project description:Tumours exhibit high genotypic and transcriptional heterogeneity. Both affect cancer progression and treatment, but have been predominantly studied separately in follicular lymphoma. To comprehensively investigate the evolution and genotype-to-phenotype maps in follicular lymphoma, we introduce CaClust, a probabilistic graphical model integrating deep whole exome, single-cell RNA and B-cell receptor sequencing data to infer clone genotypes, cell-to-clone mapping, and single-cell genotyping. CaClust outperforms a state-of-the-art model on simulated and patient data. In-depth analyses of single cells from four samples showcase effects of driver mutations, follicular lymphoma evolution, possible therapeutic targets, and single-cell genotyping that agrees with an independent targeted resequencing experiment.

2024-10-03 | GSE252642 | GEO

CaClust: linking genotype to transcriptional heterogeneity of follicular lymphoma using BCR and exomic variants (K6B)

2024-10-03 | GSE252416 | GEO

CaClust: linking genotype to transcriptional heterogeneity of follicular lymphoma using BCR and exomic variants (K7B)

2024-10-03 | GSE252344 | GEO

CaClust: linking genotype to transcriptional heterogeneity of follicular lymphoma using BCR and exomic variants (K4B)

2024-10-03 | GSE252687 | GEO

Drug-driven phenotypic convergence supports rational treatment strategies of chronic infections

Project description:Chronic Pseudomonas aeruginosa infections evades antibiotic therapy and are associated with mortality in cystic fibrosis (CF) patients. We find that in vitro resistance evolution of P.aeruginosa towards clinically relevant antibiotics leads to phenotypic convergence towards distinct states. These states are associated with collateral sensitivity towards several antibiotic classes and encoded by mutations in antibiotic resistance genes, including transcriptional regulator nfxB. Longitudinal analysis of isolates from CF patients reveals similar and defined phenotypic states, which are associated with extinction of specific sub-lineages in patients. In depth investigation of chronic P.aeruginosa populations in a CF patient during antibiotic therapy revealed dramatic genotypic and phenotypic convergence. Notably, fluoroquinolone-resistant subpopulations harboring nfxB mutations were eradicated by antibiotic therapy as predicted by our in vitro data. This study supports the hypothesis that antibiotic treatment of chronic infections can be optimized by targeting phenotypic states associated with specific mutations to improve treatment success in chronic infections.

2018-10-23 | PXD007972 | Pride

Transcriptome profiling of embryonic development rate in rainbow trout advance backcross introgression lines

Project description:Embryonic development rate is a key trait significantly associated and genetically linked with both growth rate and sexual maturity in rainbow trout. To identify candidate genes underlying embryonic development rate, whole genome expression microarray analyses were conducted using embryos from a fourth generation backcross family; each backcross generation involved the introgression of the fast-developing alleles for the major development rate QTL (from the Clearwater clonal line [CW]) into a slow-developing clonal line (Oregon State University [OSU]). Embryos were collected at 15, 19, and 28 days post-fertilization. Microsatellite markers (One112ADFG, OMM1009 and OmyFGT12TUF) linked to the major embryonic development rate QTL region were used to determine the QTL genotype. The sex marker OMY-Y1 was used to determine the genotypic sex of each embryo. cDNA from 48 individual embryos were used for microarray expression analysis. An ANOVA modeling approach was used to detect differential gene expression between embryos possessing fast-developing genotypes and slow-developing genotypes. A total of 182 features have been identified with significant differences between embryonic development rate genotypes. Quantitative PCR was conducted on ten representative genes using the rainbow trout homologous sequences and microarray results were validated.

2009-11-12 | GSE13570 | GEO

Affymetrix copy number data for melanoma cell line mapping

Project description:We searched for putative phenotypic and genotypic differences between primary lesions and melanoma metastasis. Therefore, we investigated melanoma cells derived either from the primary tumor or from lymph node metastasis of the same individual patient. In vitro studies revealed high migratory and anchorage-independent growth of metastasis-derived cells. Unexpectedly, whole genome DNA analysis displayed a total of 10 homozygous losses in the primum-derived cell line, whereas the metastasis–derived cell line only shared 5 of those losses. We further tested these cells in a mouse model for intradermal melanoma growth and detected fast growth of the metastasis-derived cell line and delayed growth of primum-derived cells. However, after re-grafting of primum-derived cells, tumor growth kinetic was accelerated and therefore comparable to metastasis-derived cells. Moreover, re-grafted primum-derived cells now also harboured the same reduced DNA deletion pattern, identical to human metastasis-derived cells. We conclude that our xenotransplantation model mimics clonal selection from a heterogeneous starting population, and we suggest that tumor cell progression at the metastatic niche can occur parallel and independently from the primary tumor. Therefore, we propose that for mutation-targeted therapy approaches, the genotyping procedure should include primary as well as metastatic melanoma biopsies. DNA was extracted from in vitro grown cell lines, and Affymetrix SNP6.0 arrays were performed according to the manufacturer's instructions. Intensity Log2 ratios were used to manually search for homozygous deletions via the genotyping console.

2011-04-07 | E-GEOD-22461 | biostudies-arrayexpress

Impaired T cell and neoantigen retention in time serial analysis of lung cancer patients treated with TIL cell therapy

Project description:Cell therapy with tumor-infiltrating lymphocytes (TIL) has yielded durable responses for multiple cancer types, but the causes of therapeutic resistance remain largely unknown. Here multi-dimensional analysis was performed on time serial tumor and blood in a lung cancer TIL therapy trial. Using T-cell receptor sequencing on both functionally expanded T cells and neoantigen-loaded tetramer-sorted T cells, we identified neoantigen specific TCRs. We then mapped clones into individual transcriptomes and found that neoantigen-reactive clonotypes expressed a dysfunctional program and lacked stem-like features among patients who lacked clinical benefit. Tracking neoantigen-reactive clonotypes over time, decay of antigen-reactive peripheral T-cell clonotypes was associated with the emergence of progressive disease. Further, subclonal neoantigens previously targeted by infused T cells were subsequently absent within tumors at progression, suggesting potential adaptive resistance. Our findings suggest that targeting clonal antigens and circumventing dysfunctional states may be important for conferring clinical responses to TIL therapy.

2024-12-30 | PXD049438 | Pride

Expression patterns in time and space during P.sojae infection of soybean cultivars differing in quantitative resistance

Project description:Four selected soybean genotypes with varying degrees of quantitative resistance that were well-characterized were selected for this study. These included two resistant genotypes (V71-370, Conrad), and two susceptible genotypes (Sloan, and VP-RIL9). A P. sojae isolate, PT2004C2.S1 , which is virulent to the soybean genotypes carrying Rps1a, Rps1b, Rps1k, Rps2, Rps3a, Rps3c, Rps4, Rps5, Rps6, or Rps7, was used in this study. Keywords: Genotypic variation on quantitative resistance

2007-11-26 | GSE9687 | GEO

cowpea: short-podded pools vs. long-podded pools

Project description:Microarray hybridizations of a long-pod and a short-pod pool, each consisting of RNA from seven independent genotypes, were performed to reveal the gene regulatory basis underlying the genotypic pod length difference.

2017-04-30 | GSE80552 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data