A Proteogenomic Analysis of Cervical Cancer Reveals Therapeutic and Biological Insights
Ontology highlight
ABSTRACT:
INSTRUMENT(S):
ORGANISM(S): Homo Sapiens (human)
SUBMITTER: 
Zhicheng Yang
LAB HEAD: Hu Zhou
PROVIDER: PXD055203 | Pride | 2024-10-09
REPOSITORIES: Pride
Dataset's files
Items per page: 5 1 - 5 of 165 |
Similar Datasets
Project description:PIP2 enhances MLKL channel activity in a direct interaction manner and this gain of function promotes both necroptosis and inflammation. Previous studies have reported that phospholipids assisted MLKL recruitment and translocation which facilitates its mediated function like liposome leaking. Here, our result support MLKL act as ion channel and is finely tuned by PIP2. In the immune process especially, PIP2, as an important modulator, promotes intracellular potassium depletion and trigger inflammation which mediated bythrough MLKL channel function. Defining the role of MLKL channel function in MLKL-induced necroptosis or other potential necroptotic models will extend our understanding of the programmed cell death and critically inform the development and testing of new disease-specific, Anti-inflammatory, therapeutic strategies.
2022-11-05 | PXD030814 | Pride
Project description:Co-fractionation mass spectrometry experiments (CF-MS) using native-like protein separations such as Blue Native electrophoresis (BNE) or size exclusion chromatography (SEC) enable a global characterization of protein networks, and a better understanding of cellular functions. They do, however, pose significant requirements on sample amounts, on wet lab and on instrument time, which frequently renders statistically useful replication or comparative experiments between multiple biological states non-feasible. Here we present a fast workflow called mini-Complexome Profiling (mCP) for global targeted detection of annotated protein-protein complexes. It comprises mild extraction of complexes, fractionation by BNE and analysis by data independent acquisition mass spectrometry (DIA-MS). Of note, BNE fractionation into 35 fractions is achieved using commercial mini-gels, with minimal requirements on sample amounts. Complexes are detected using a novel, bespoke R package with a controlled false discovery rate (FDR) approach. The tool is available to the community on a Github repository (https://github.com/hugoagno3/mCP ). We first benchmarked our workflow using Hek293 cell lysates as a well established cell line model. We then challenged mCP by investigating changes in the complexome of mouse cardiomyocytes isolated from different heart cavities of single mice. In these challenging and limited samples we detected 48 annotated protein complexes per compartment on average and were able to perform differential inter-cavity comparisons from single animals. These reduced sample and instrument time requirements suggest the suitability of our workflow for complexome screening in sparse samples, e.g. in human patient biopsies.
2024-07-25 | PXD049340 | Pride
Project description:Co-fractionation mass spectrometry experiments (CF-MS) using native-like protein separations such as Blue Native electrophoresis (BNE) or size exclusion chromatography (SEC) enable a global characterization of protein networks, and a better understanding of cellular functions. They do, however, pose significant requirements on sample amounts, on wet lab and on instrument time, which frequently renders statistically useful replication or comparative experiments between multiple biological states non-feasible. Here we present a fast workflow called mini-Complexome Profiling (mCP) for global targeted detection of annotated protein-protein complexes. It comprises mild extraction of complexes, fractionation by BNE and analysis by data independent acquisition mass spectrometry (DIA-MS). Of note, BNE fractionation into 35 fractions is achieved using commercial mini-gels, with minimal requirements on sample amounts. Complexes are detected using a novel, bespoke R package with a controlled false discovery rate (FDR) approach. The tool is available to the community on a Github repository (https://github.com/hugoagno3/mCP ).
2024-07-25 | PXD049426 | Pride
Project description:Discovery of human leukocyte antigen (HLA) class I presented peptides of bacterial origin is essential to discover bacterial antigen targets as putative vaccine constituents. However, reliable identification of such HLA-presented bacterial epitopes are extremely low abundant compared to the host proteome. Here, we describe an upgraded bioinformatical workflow to enhance the confident detection of bacterial immunopeptides. Re-analysis of Listeria monocytogenes (Listeria)-infected cell cultures was searched by four search engines in parallel with follow-up by rescoring by MS2Rescore and integration of all search results. Boosting identification by both rescoring and integration, this delivered an additional 18 Listeria peptides (+26.5%) matching 15 different proteins (+35.7%) compared to the initial analysis. Moreover, conflicts between search engine results uncovered ambiguities in spectra-to-peptide assignments, in some cases with spectra assigned to human and Listeria peptides. Finally, we demonstrate how our workflow is compatible with timsTOF data acquisition, incorporating rescoring of ion mobility features using TIMS2Rescore.
2025-02-05 | PXD055547 | Pride
Project description:Comparative transcriptome analyses revealed 69 genes exhibiting ?2-fold mRNA level changes in C. glutamicum DfkpA.Overall, 34 genes exhibited ?2-fold increased and 35 genes at least 0.5-fold decreased mRNA levels in JVO1 DfkpA. About half of these genes (32) encode for hypothetical/putative proteins. LdhA encoding L-lactate dehydrogenase exhibited by far the strongest increased mRNA level (8.5-fold) in the absence of FkpA. Determination of the respective specific LdhA activities revealed about 2-fold increased activity in JVO1 DfkpA (0.73 ± 0.05 U/mg) compared to the reference JVO1 (0.41 ± 0.02 U/mg). Notably, the two short gene lists include four genes encoding transcriptional regulators exhibiting increased mRNA levels (farR, lexA, divS, znr) and two exhibiting decreased mRNA levels (ramB, mmpLR) in the absence of FkpA under the conditions tested. The mRNA level of cysK was increased (2.05-fold) which is repressed by RamB whose mRNA level was decreased (0.27-fold). In contrast, the mRNA level of RamB-repressed ald was decreased (0.31-fold) and not increased. To identify the influence of PPIase FkpA on global gene expression, DNA microarray analyses were performed with a ?fkpA mutant compared to the reference C. glutamicum JVO1. For this purpose RNA was isolated from exponentially growing cells cultivated in CgXII minimal medium with 4% glucose at increased temperature (35°C) above growth optimum of C. glutamicum. Two biological replicates were performed with each representing an intra-array duplicate.
2015-09-08 | E-GEOD-65294 | biostudies-arrayexpress
Project description:The plant hormone gibberellin (GA) represents an important regulator of growth and development. Early transcriptional events controlled by GA are not well characterised. Previous microarray studies have identified genes responsive to GA treatment in the whole seedling. The whole seedling represents many tissues where subtle effects of GA treatment in specific tissues may be masked. When treated with GA, an effect on the growth rate of roots was observed. More specifically, the shorter root of a GA-deficient plant can be rescued to wild-type length by the application of GA. This experiment was designed to identify GA-regulated genes in the root tips of Arabidopsis. The use of a GA-deficient mutant provides a greater potential to identify genes responding to GA treatment. Root tips are ideally suited for the quick uptake of the hormone treatment. There will be two biological replicates which will each consist of a control treatment at 0 minutes and 2 hours, as well as the experimental GA-treated 2 hour time point. This system provides an opportunity to compare gene expression between treated and non-treated root tips and allow the identification of early GA-responsive genes. 6 samples were used in this experiment.
2010-04-28 | E-GEOD-20223 | biostudies-arrayexpress
Project description:The study of rare pediatric disorders is fundamentally limited by small patient numbers, making it challenging to draw meaningful conclusions about their molecular basis. To address this, we developed a framework that integrates clinical ontologies with proteomic profiling, enabling the systematic analysis of rare conditions in aggregate rather than isolation. We demonstrated this approach by analyzing urine and plasma samples from 1,140 children and adolescents, encompassing 394 distinct disease conditions and healthy controls. Using advanced mass spectrometry workflows, we achieved deep proteome coverage with over 5,000 proteins quantified in urine and 900 in plasma. By embedding SNOMED CT clinical terminology in a network structure and connecting it to proteomic data, we could group rare conditions based on their clinical relationships, allowing statistical analysis even for diseases with as few as two patients. This approach revealed molecular signatures across developmental stages and disease clusters while accounting for age- and sex-specific variation. Our framework provides a generalizable solution for studying heterogeneous patient populations where traditional case-control studies are impractical, bridging the gap between clinical classification and molecular profiling of rare diseases.
2025-06-10 | PXD058960 | Pride
Project description:Cancer cells rely on mitochondria for their bioenergetic supply and macromolecule synthesis. Central to mitochondrial function is the regulation of mitochondrial protein synthesis, which primarily depends on the cytoplasmic translation of nuclear-encoded mitochondrial mRNAs whose protein products are imported into mitochondria. Despite the growing evidence that mitochondrial protein synthesis contributes to the onset and progression of cancer, and offers new opportunities for cancer therapy, knowledge of the underlying molecular mechanisms remains limited. Here, we show that RNA G-quadruplexes (RG4s) are co-localized with mitochondria and regulate mitochondrial function by modulating cytoplasmic mRNA translation of nuclear- encoded mitochondrial proteins. Our data support a model whereby the RG4 folding dynamics, under the control of oncogenic signaling and modulated by small molecule ligands or RG4-binding proteins, modifies mitochondria-localized cytoplasmic protein synthesis. Ultimately, this impairs mitochondrial functions, affecting energy metabolism and consequently cancer cell proliferation.
2025-05-06 | PXD046236 | Pride
Project description:Cancer cells rely on mitochondria for their bioenergetic supply and macromolecule synthesis. Central to mitochondrial function is the regulation of mitochondrial protein synthesis, which primarily depends on the cytoplasmic translation of nuclear-encoded mitochondrial mRNAs whose protein products are imported into mitochondria. Despite the growing evidence that mitochondrial protein synthesis contributes to the onset and progression of cancer, and offers new opportunities for cancer therapy, knowledge of the underlying molecular mechanisms remains limited. Here, we show that RNA G-quadruplexes (RG4s) are co-localized with mitochondria and regulate mitochondrial function by modulating cytoplasmic mRNA translation of nuclear- encoded mitochondrial proteins. Our data support a model whereby the RG4 folding dynamics, under the control of oncogenic signaling and modulated by small molecule ligands or RG4-binding proteins, modifies mitochondria-localized cytoplasmic protein synthesis. Ultimately, this impairs mitochondrial functions, affecting energy metabolism and consequently cancer cell proliferation.
2025-05-06 | PXD046213 | Pride
Project description:Determine the role of MyD88 during stimulation of macrophages with trehalose dimycolate (TDM)-coated beads by comparison of murine macrophage from wild-type and MyD88 knockout mice.
2013-02-20 | E-MEXP-3815 | biostudies-arrayexpress