Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Exon sequencing of mouse tails and respective tumors from mice with VBPN genetic background

ABSTRACT: BRAF mutant colorectal cancer displays a unmet clinical need with poor overall survival. Here we modeled this cancer in the murine system with Braf activation mutation, Trp53 deletion and Nicd1 expression. The respective alleles are recombined in the intestinal epithelium upon systemic tamoxifen injection. Tumors were occuring in the small intestine and in the colon. We conducted exon sequencing to investigate if other mutations occur in the tumor development.

INSTRUMENT(S): Illumina NovaSeq 6000

ORGANISM(S): Mus musculus

SUBMITTER: Manuel Mastel

PROVIDER: E-MTAB-17103 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Whole exome sequencing grid of untreated, TPA-treated, and DMBA+TPA-treated mouse back skin

Project description:We generated meso-scale grids from mouse back skin by collecting paired whole-exome sequencing (WES) and bulk RNA sequencing (bulk RNA), retaining coordinate information to preserve spatial context across the grids. Grids were derived from untreated mice (UN, n = 4), mice treated with the cell-cycle activator TPA for twelve weeks (TO, n = 3), and mice treated with the carcinogen DMBA followed by repeated TPA until the first visible papilloma (DT, n = 3). Cumulatively, we collected 690 bulk RNA and 476 WES samples, the majority of which are paired. All DT animals developed papillomas, whereas no macroscopic skin alterations were observed in UN or TO mice.

2026-06-11 | E-MTAB-15745 | biostudies-arrayexpress

RNAi profiling of primary human AML cells identifies ROCK1 as a therapeutic target and nominates Fasudil as an anti-leukemic drug.

Project description:Acute myeloid leukemia (AML) is characterized by a marked genetic heterogeneity, which complicates the development of novel therapeutics. The delineation of pathways essential within the patient-individual mutational background might overcome this limitation and facilitate personalized treatment. We report the results of a large-scale lentiviral loss-offunction RNA-interference-(RNAi)-screen in primary leukemic cells. Stringent validation identified six genes (BNIPL1, ROCK1, RPS13, STK3, SNX27, WDHD1) whose knockdown impaired growth and viability of the cells. Dependence on these genes was not caused by mutation or overexpression and while some of the candidates seemed to be rather patientspecific, others were essential in cells isolated from other AML patients. In addition to the phenotype observed after ROCK1 knockdown, treatment with the approved ROCK-inhibitor fasudil resulted in increased apoptosis and decreased viability of primary AML cells. In contrast to observations in some other malignancies, ROCK1-inhibition did not foster growth of immature malignant progenitors; but was also toxic to this cell fraction in feeder-co-culture and xenotransplantion experiments, indicating a distinct effect of ROCK1 inhibition on leukemic progenitors. We conclude that large scale RNAi screens in primary patient-derived cells are feasible and can complement other methods for personalized cancer therapies, such as expression and mutation profiling. Large-scale lentiviral loss-of-function shRNA screen in primary leukemic cells with two time points, exome sequencing of primary leukemic cells, and a gene expression profiling of primary cells from four leukemic and three healthy samples.

2015-05-16 | E-GEOD-68925 | biostudies-arrayexpress

Whole exome sequencing of human MDS/AML OCI-M2 and patient-derived bone marrow cell lines treated with 5-azacytidine

Project description:The whole exome sequencing experiment is part of the study: “Analysis of 5-azacytidine resistance models reveals a set of targetable pathways”. In the study we generated myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) OCI-M2 cell lines as well as patient-derived bone marrow cell lines that are resistant to hypomethylating therapy by 5-azacytidine (AZA). By integrated analysis of expression and mutation data obtained from these samples we have identified multiple signaling pathways whose modulation by specific small molecule inhibitors significantly block proliferation of AZA-resistant cell lines without increasing their sensitivity to AZA. The understanding of the molecular mechanisms which characterize the AZA-R phenotype can be used for broadening therapeutic options at progressing states during AZA therapy.

2022-05-02 | E-MTAB-11172 | biostudies-arrayexpress

Correction of human phospholamban R14del mutation associated with cardiomyopathy using targeted nucleases and combination therapy [Exome-Seq]

Project description:Phospholamban R14del mutazion (PLN-R14del) has been identified in a large family pedigree in which heterozygous carriers exhibited inherited dilated cardiomyopathy (DCM) and death by middle age. To better understand the causal link between the mutations in PLN and DCM pathology, we derived induced pluripotent stem cells from a DCM patient carrying the PLN R14del mutation. We showed that iPSC-derived cardiomyocytes recapitulated the DCM-specific phenotype and demonstrated that either TALEN-mediated genetic correction or combinatorial gene therapy resulted in phenotypic rescue. Our findings offer novel insights into the pathogenesis caused by mutant PLN and point to the development of potential new therapeutics of pathogenic genetic variants associated with inherited cardiomyopathies. Submitter confirms there are no patient privacy concerns with these data. iPSCs were derived from a female patient carrying a heterozygous mutation (R14del) in the PLN gene. Tree samples were analyzed: R14del-CMs (clone L2), corrected R14del-CMs (clone L2GC1) and corrected R14del-CMs (clone L2GC2)

2015-02-09 | E-GEOD-65762 | biostudies-arrayexpress

Seq_MDH2

Project description:Whole exome sequencing identification of MDH2 mutations in a patient with multiple and malignant paragangliomas

2015-06-01 | E-MTAB-2422 | biostudies-arrayexpress

Single-cell RNA-seq of human primary pDCs before and after 24 h stimulation with TLR9 agonist cytosine-phosphate-guanine (CpG) oligodeoxynucleotide

Project description:Plasmacytoid dendritic cells (pDCs) are a rare immune cell population that plays a key role in antiviral innate immunity. In our analysis, secretin (SCT) emerged as one of the most highly expressed hormones in both circulating and tissue-resident pDCs. To validate this finding, we performed spatial transcriptomic analysis of adult tonsil tissue, which demonstrated co-localization of SCT transcripts with the pDC marker LILR4A. We further confirmed SCT expression at the protein level by immunofluorescence staining of primary human peripheral blood pDCs, showing co-expression of secretin with the canonical pDC markers CLEC4C and TLR9. In a longitudinal single-cell RNA-sequencing dataset from individuals with COVID-19, we observed modest upregulation of SCT in interferon-activated pDCs. To determine whether SCT expression is linked to immune function, we purchased primary human peripheral blood pDCs and stimulated them in vitro with the TLR9 agonist cytosine-phosphate-guanine (CpG) oligodeoxynucleotide, followed by single-cell transcriptomic profiling.

2026-05-22 | E-MTAB-16728 | biostudies-arrayexpress

Proteogenomic analysis unveils the expression of cancer associated and specific antigen-derived HLA Class ǀ immunopeptides in melanoma and EGFR mutant lung adenocarcinoma

Project description:Immunotherapy has shown great therapeutic potential for cancers with high tumor mutational burden (TMB), but much less promise for cancers with low TMB. One primary approach for adoptive lymphocyte transfer-based immunotherapy is to target the somatic mutated peptide neoantigens and cancer testis (CT) antigens recognized by cytotoxic T cells. Here, we employed mass spectrometry (MS)-based proteogenomic large-scale profiling to identify potential immunogenic human leukocyte antigen (HLA) Class ǀ- associated peptides in both melanoma, a “hot tumor”, and EGFR mutant lung adenocarcinoma, a “cold tumor”. We uncovered 19 common driver oncogene-derived peptides and more than 1000 post-translationally modified peptides (PTM) representing 58 different PTMs. We constructed a CT antigen database with 286 antigens by compiling reputed CT antigen resources and “in-house” genomic data and used this to identify 45 CT antigen-derived peptides from the identified HLA peptidome. Using integrated next generation sequencing data, we discovered 12 neopeptides in EGFR mutant lung cancer cell lines. Finally, we report a novel approach for non-canonical peptide discovery, whereby we leveraged a deep learning-based de novo search and a high confidence annotated long noncoding RNA (LncRNA) database to identify 44 lncRNA-derived peptides. Findings of this study, for the first time, provide evidence for a large pool of actionable cancer antigen-derived peptides for use in mutant EGFR lung cancer immunotherapy.

2021-12-07 | PXD019774 | Pride

Soluble Guanylate Cyclase Signalling Mediates Etoposide Resistance in Progressing Small Cell Lung Cancer

Project description:We exploited six paired pre-treatment and post-chemotherapy circulating tumour cell patient-derived explant (CDX) models from donors with extensive stage SCLC to investigate changes at disease progression after chemotherapy. WES data from the patient germ line and from the biopsy of the solid tumour is reported in this submission and RNASeq data from these models is reported previously (E-MTAB-8465 - RNA of Small Cell Lung Cancer Circulating Tumour Cells Derived Explants). Both chemo naive and progression models were taken from patients and their drug sensitivity tested within the mouse models. Blood samples were taken from patients, and RosetteSep CTC Enrichment was used to implant these cells into mice. Tumours were allowed to grow, then extracted and re-implanted into second and third generations of mice, before finally being subjected to molecular profiling.

2021-09-15 | E-MTAB-10880 | biostudies-arrayexpress

Proteogenomic analysis unveils the HLA Class I presented immunopeptidome in melanoma and EGFR mutant lung adenocarcinoma

Project description:Immune checkpoint inhibitor and adoptive lymphocyte transfer-based therapies have shown great therapeutic potential for cancers with high tumor mutation burden (TMB). Here, we employed mass spectrometry (MS)-based proteogenomic large-scale profiling to identify potential immunogenic human leukocyte antigen (HLA) Class ǀ-presented peptides in both melanoma, a “hot tumor” with high TMB, and EGFR mutant lung adenocarcinoma, a “cold tumor” with low TMB. We used cell line and patient-specific databases constructed using variants identified from whole-exome sequencing, as well as a de novo search algorithm from the PEAKS search algorithm to interrogate the mass spectrometry data of the Class I immunopeptidome. We identified 12 mutant neoantigens. Several classes of tumor-associated antigen-derived peptides were also identified. We constructed a cancer germline (CG) antigen database with 285 antigens and identified 42 Class I-presented CG antigens. We identified more than 1000 post-translationally modified (PTM) peptides representing 58 different PTMs. Our results suggest that PTMs play a critical role impacting HLA-binding affinity dramatically. Finally, leveraging de novo search and an annotated lncRNA database, we developed a novel non-canonical peptide discovery pipeline to identify 44 lncRNA-derived peptides that are presented by Class I. We validated MS/MS spectra of select peptides using synthetic peptides and performed HLA Class I binding assays to demonstrate binding of select neo-peptides and lncRNA-derived peptides to Class I proteins. In summary, we provide direct evidence of HLA Class I presentation of a large number of mutant and tumor-associated peptides for potential use as vaccine or adoptive cell therapy in melanoma and EGFR mutant lung cancer.

2021-08-23 | PXD022949 | Pride

Genotyping by whole-exome sequencing of human with hereditary pheochromocytoma

Project description:Whole exome sequencing identification of Max mutations and further validation in pheochromocytoma patients

2012-03-01 | E-MTAB-591 | biostudies-arrayexpress