Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Proteogenomic analysis of Human acute myeloid leukemia

ABSTRACT: Here, we used OpenCustomDB, a web-based tool that uses both sample-specific RNAseq data to identify genomic variants and the OpenProt resource that annotates alternative proteins in addition to canonical proteins. We tested OpenCustomDB with a cohort of 17 patients with acute myeloid leukemia and detected 3026 peptides from alternative proteins, including 208 variants in LC-MS/MS.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Cell, Blood

DISEASE(S): Acute Leukemia

SUBMITTER: Noé Guilloy

LAB HEAD: Xavier Roucou

PROVIDER: PXD029240 | Pride | 2023-05-10

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	AML_P01_G1_F1.raw	Raw
	AML_P01_G1_F2.raw	Raw
	AML_P01_G1_F3.raw	Raw
	AML_P01_G1_F4.raw	Raw
	AML_P01_G2_F1.raw	Raw

Items per page:

1 - 5 of 180

Publications

OpenCustomDB: Integration of Unannotated Open Reading Frames and Genetic Variants to Generate More Comprehensive Customized Protein Databases.

Guilloy Noé N Brunet Marie A MA Leblanc Sébastien S Jacques Jean-François JF Hardy Marie-Pierre MP Ehx Grégory G Lanoix Joël J Thibault Pierre P Perreault Claude C Roucou Xavier X

Journal of proteome research 20230324 5

Proteomic diversity in biological samples can be characterized by mass spectrometry (MS)-based proteomics using customized protein databases generated from sets of transcripts previously detected by RNA-seq. This diversity has only been increased by the recent discovery that many translated alternative open reading frames rest unannotated at unsuspected locations of mRNAs and ncRNAs. These novel protein products, termed alternative proteins, have been left out of all previous custom database gen ...[more]

PMID: 36961377

Similar Datasets

Optimized Sample Preparation Workflow for Improved Identification of Ghost Proteins

Project description:Large scale proteomic strategies rely on database interrogation. Thus, only referenced proteins can be identified. Recently, Alternative Proteins (AltProts) translated from nonannotated Alternative Open reading frame (AltORFs) were discovered using customized databases. Because of their small size which confers them peptide-like physicochemical properties, they are more difficult to detect using standard proteomics strategies. In this study, we tested different preparation workflows for improving the identification of AltProts in NCH82 human glioma cell line. The highest number of identified AltProts was achieved with RIPA buffer or boiling water extraction followed by acetic acid precipitation.

2021-02-15 | PXD024134 | Pride

Mislocalization of pathogenic RBM20 variants in dilated cardiomyopathy is caused by loss-of-interaction with Transportin-3

Project description:Severe forms of dilated cardiomyopathy (DCM) are associated with point mutations in the alternative splicing regulator RBM20 that are frequently located in the arginine/serine-rich domain (RS-domain). Such mutations can cause defective splicing and cytoplasmic mislocalization, which leads to the formation of detrimental cytoplasmic granules. Successful development of personalized therapies requires identifying the direct mechanisms of pathogenic RBM20 variants. Here, we decipher the molecular mechanism of RBM20 mislocalization and its specific role in DCM pathogenesis. We demonstrate that mislocalized RBM20 variants retain their splice regulatory activity, which reveals that aberrant cellular localization drives the pathological phenotype. A genome-wide CRISPR knock-out screen combined with image-enabled cell sorting identified Transportin-3 (TNPO3) as the main nuclear importer of RBM20. We show that the direct RBM20-TNPO3 interaction involves the RS-domain, disrupted by pathogenic variants. Re-localization of pathogenic RBM20 variants to the nucleus restores alternative splicing and dissolves cytoplasmic granules in cell culture and animal models. These findings provide proof-of-principle for developing therapeutic strategies to restore RBM20’s nuclear localization in RBM20-DCM patients.

2023-06-19 | PXD038790 | Pride

Probing the Function of Alternative Proteins in Cell Reprogramming by Large Scale Proteomics and Cross - Linking Mass Spectrometry

Project description:Many proteins are lacking from reference databases because they are issued from alternative ORFs neither respecting the rules decreed for the genome annotation or for the protein translation from mRNA. It was evidenced that not only a single protein is therefore translated from an mRNA. However, the function of these Alternative Proteins (AltProts) remain largely unknown. Here, we were interested by looking to the function of AltProts in the context of cancer cell reprogramming. We have developed a large scale approach based on shot-gun proteomics and cross-linking mass spectrometry (XL-MS) to identify the regulation of the reference proteins (RefProts) versus the AltProts and find the their interaction partners. The study was conducted from NCH82 human glioma cells which were stimulated by the protein kinase A (PKA) activator Forskolin upon 16H, 24H and 48H to induce cell differentiation and epithelial-mesenchymal transition (EMT). The data have shown to enable tracing back the function of the AltProts by combining experimental data to in silico analysis using cytoscape with ClueGo for GO Term annotation and enrichment of pathways with String. Very interestingly many AltProts demonstrate to be involved in the regulation of tRNA through their interaction with aaRS proteins and of the cellular mobility.

2021-02-15 | PXD014642 | Pride

Karlsson_et_al_OSA

Project description:This experiment was conducted to generate targeted resequencing data covering a region associated with osteosarcoma in greyhounds. 8 greyhounds diagnosed with osteosarcoma and 7 greyhounds without tumors were sequenced. DNA from the 15 dogs was used to prepare libraries and hybrid capture performed to enrich the region of interest prior to paired-end sequencing using Illumina Genome Analyzer II. The reads were aligned to the dog-genome CanFam2.0 using bwa and pre-processed using Picard and GATK. Variant discovery was performed using GATK. The resulting list of variants were used in the study to finemap the associated region and look for causal variants. We submit the preprocessed BAM-files that still have all reads although some reads are flagged. We also submit the resulting vcf-file with called and filtered variants in all individuals.

2013-11-16 | E-MTAB-1984 | biostudies-arrayexpress

A novel class of CLK kinases inhibitors that target SRSF10 and promote p53mediated cytotoxicity on human colorectal cancer cells

Project description:The elevated expression of the splicing regulator SRSF10 in metastatic colorectal cancer (CRC) stimulates the production of the pro-tumorigenic Bclaf1-L splice variant. We discovered a group of small molecules with an aminothiazole carboxamide core (GPS167, GPS192 and others) that decrease production of Bclaf1-L. While additional alternative splicing events regulated by SRSF10 are affected by GPS167/192 in HCT116 cells (e.g., in MDM4, WTAP, SLK1 and CLK1), other events are shifted in a SRSF10-independent manner (e.g., in MDM2, NAB2 and TRA2A). GPS167/192 increased the interaction of SRSF10 with the CLK1 and CLK4 kinases, leading us to show that GPS167/192 are CLK kinase inhibitors preferentially impacting the activity of SRSF10. Notably, GPS167 impairs the growth of CRC cell lines and organoids, inhibits anchorage-independent colony formation, cell migration, and promotes cytoxicity that requires SRSF10 and p53. In contrast, GPS167 only minimally affects normal colonocytes and normal colorectal organoids. Thus, GPS167 reprograms the tumorigenic activity of SRSF10 in CRC cells to elicit p53-dependent apoptosis.

2021-09-09 | PXD022333 | Pride

Timeline of changes in spike conformational dynamics in emergent SARS-CoV-2 variants reveal progressive stabilization of trimer stalk with altered NTD dynamics

Project description:SARS-CoV-2 emergent variants are characterized by increased viral fitness and each shows multiple mutations predominantly localized to the spike (S) protein. Here, amide hydrogen/deuterium exchange mass spectrometry has been applied to track changes in S dynamics from multiple SARS-CoV-2 variants. Our results highlight large differences across variants at two loci with impacts on S dynamics and stability. A significant enhancement in stabilization first occurred with the emergence of D614G S followed by smaller, progressive stabilization in subsequent variants. Stabilization preceded altered dynamics in the N-terminal domain, wherein Omicron BA.1 S showed the largest magnitude increases relative to other preceding variants. Changes in stabilization and dynamics resulting from S mutations detail the evolutionary trajectory of S in emerging variants. These carry major implications for SARS-CoV-2 viral fitness and offer new insights into variant-specific therapeutic development.

2023-03-14 | PXD040717 | Pride

Proteogenomics of malignant melanoma cell lines: searching for genetically encoded point mutations in LC-MS/MS data

Project description:In this study we performed proteogenomic analysis for 9 cell lines of malignant melanoma. The main objectives of the study were identifying the variants originating from point mutations and analyzing the effect of exome data filtering on the outcome of variant identification.

2018-12-05 | PXD007662 | Pride

Granulins rescue inflammation, lysosome dysfunction, and neuropathology in a mouse model of progranulin deficiency

Project description:In this study, we investigate whether individual granulin subunits derived from the precursor protein progranulin are beneficial. We test this by asking if delivery of a single granulin to the brains of a preclinical model of FTD-GRN Grn-/-mice is sufficient to ameliorate disease-like phenotypes. We performed intracerebroventricular injections of recombinant adeno-associated virus (rAAV2/1) encoding granulin-2, granulin-4, full-length PGRN or GFP in neonatal Grn+/+ and Grn-/- mice. Following AAV injections, mice were aged for 12 months, tissues collected, and analyzed. Quantitative proteomics of the thalamus identified lysosomal function and neuroinflammation as pathways ameliorated by the expression of granulins. Biochemical markers of lysosomal dysfunction, neuroinflammation, and disease-like pathology were assessed via immunoblot and immunohistochemistry. We found that both granulin-2 and granulin-4 rescue markers of lysosomal dysfunction and neuroinflammation in cortical, hippocampal, and thalamic tissue.

2024-10-15 | PXD041095 | Pride

An integrated transcriptome and expressed variant analysis of sepsis survival and death

Project description:Background: Sepsis, a leading cause of morbidity and mortality, is not a homogeneous disease but rather a syndrome encompassing many heterogeneous pathophysiologies. Patient factors including genetics predispose to poor outcomes, though current clinical characterizations fail to identify those at greatest risk of progression and mortality. Results: The Community Acquired Pneumonia and Sepsis Outcome Diagnostic study enrolled 1,152 subjects with suspected sepsis. We sequenced peripheral blood RNA of 129 representative subjects with systemic inflammatory response syndrome (SIRS) or sepsis (infection with SIRS), including 78 sepsis survivors and 28 sepsis nonsurvivors, who had previously undergone plasma proteomic and metabolomic profiling. The expression of 338 genes differed between subjects with SIRS and those with sepsis, primarily reflective of immune activation in sepsis. The expression of 1,238 genes differed with sepsis outcome: Nonsurvivors had lower expression of many immune function-related genes. Functional genetic variants associated with sepsis mortality were sought based on a common disease â rare variant hypothesis. VPS9D1, whose expression was increased in sepsis survivors, had a higher burden of missense variants in sepsis survivors, and these were associated with altered expression of 3,799 genes, primarily reflecting Golgi and endosome biology. Conclusions: Host response in sepsis survivors â activation of immune response-related genes â was muted in sepsis nonsurvivors. The association of sepsis survival with robust immune response and presence of missense variants in VPS9D1 warrants replication and further functional studies. We sequenced peripheral blood RNA of 129 representative subjects with systemic inflammatory response syndrome (SIRS, n=23) or sepsis (infection with SIRS), including 78 sepsis survivors and 28 sepsis nonsurvivors, who had previously undergone plasma proteomic and metabolomic profiling.

2015-01-01 | E-GEOD-63042 | biostudies-arrayexpress

IgG from systemic sclerosis patients induce a profibrosing and serotype-dependent phenotype in normal dermal fibroblast: a multi-omics study

Project description:Autoantibodies (Aab) are frequent in systemic sclerosis (SSc). While recognized as potent biomarkers, their pathogenic role is much debated. This study explored the effect of purified IgG from SSc patients on the phenotype and function of healthy dermal fibroblast (FB) using an innovative multi-omics approach.

2022-06-29 | PXD025885 | Pride

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