Modeling precision treatment of breast cancer
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Laura Heiser
PROVIDER: E-GEOD-48216 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:This information was used to identify mutations associated with particular breast cancer subtypes, as well as associations with response to therapy. 75 breast cancer cell lines underwent exome sequencing to identify mutations.
2013-08-20 | E-GEOD-48215 | biostudies-arrayexpress
Project description:56 breast cancer cell lines were profiled to identify patterns of gene expression associated with subtype and response to therapeutic compounds. Cell lines were profiled in their baseline, unperturbed state.
2013-08-20 | E-GEOD-48213 | biostudies-arrayexpress
Project description:Differential gene transcription enables development and homeostasis in all animals and is regulated by two major classes of distal cis-regulatory DNA elements (CREs), enhancers and silencers. While enhancers have been thoroughly characterized, the properties and mechansisms of silencers remain largely unknown. By an unbiased genome-wide functional screen in Drosophila melanogaster S2 cells, we discover a class of silencers that bind one of three transcription factors (TFs) and are generally not included in chromatin-defined CRE catalogs, as they mostly lack detectable DNA accessibility. The silencer-binding TF CG11247, which we term Saft, safeguards cell fate decisions in vivo and functions via a highly-conserved domain we term ZAC and the corepressor G9a, independently of G9a’s H3K9-methyltransferase activity. Overall, our identification of silencers with unexpected properties and mechanisms has important implications for the understanding and future study of repressive CREs, as well as the functional annotation of animal genomes.
2024-11-13 | PXD048161 | Pride
Project description:Objective: This study examined the ability of established brain biomarkers, glial fibrillary acid protein (GFAP), neuro-filament light chain (NFL), ubiquitin carboxy hydrolase-L1(UCH-L1), tau, and phosphorylated tau (p-tau), and novel biomark- ers from blood collected sub-acutely after concussion to determine prediction of persisting post-concussion symptoms (PPCS) beyond 3 months. We hypoth- esized that a combination of established and novel proteins would predict high PPCS burden. Participants: Adolescents 11 to 17.99 years with a concussion based on Concussion In Sport Group (CISG) criteria were eligible. Participants were assessed 7–35 days post-injury (baseline) and then reassessed at 3 months (follow-up) for persistent post-concussion symptoms (PPCS) using the Post- Concussion Symptom Inventory, 2nd Edition (PCSI-2). A total of 155 participants (78 females, 77 males) with both blood biomarkers and 3-month symptom data were analyzed. Design: Plasma proteins collected sub-acutely (7–35 days post concussion) were quantified by both Quanterix and the Olink Explore platform, and compared between participants with the highest and lowest quartiles of PPCS severity at follow-up (85–95 days post concussion) using the PCSI-2. An exhaustive best- subsets logistic regression strategy was executed following clinical and biologi- cal pre-filtering to identify parsimonious multivariable configurations of protein biomarkers distinguishing individuals with high and low PPCS at follow-up. A stratified 10-fold cross-validation framework was implemented to evaluate model generalizability and safeguard against overfitting, while bootstrapping was used to calculate confidence intervals. Ingenuity Pathway Analysis (IPA) was performed to generate hypotheses of molecular pathways implicated in PPCS pathogenesis. Results: None of the brain biomarkers collected sub-acutley were signifi- cantly different in PPCS-high and PPCS-low groups at 90-day follow-up. No Olink proteins survived multiple testing correction, but a cross-validated mul- tivariable model, including Tripartite Motif Containing 39 (TRIM39) + Sclerostin (SOST) + Transcription factor Dp family member 3 (TFDP3) + TNF receptor superfamily member 9 (TNFRSF9) + Leptin (LEP) + Prune Homolog 2 With BCH Domain (PRUNE2) + Trimethylguanosine Synthase 1 (TGS1) + EPCAM (Epithelial Cell Adhesion Molecule) distinguished high PPCS at follow-up with an area under the curve (AUC) of 0.86 (95% CI 0.80–0.92). IPA identified three significant net- works associated with PPCS: (a) cardiovascular and neurological disease, organ- ismal injury, and abnormalities (score = 45; 28 focus molecules); (b) connective tissue disorders, inflammatory disease, and organismal injury and abnormalities (score = 41; 26 focus molecules); and (c) connective tissue development and function, embryonic development, and organismal development (score = 41; 26 focus molecules). Conclusion: This study suggests the possibility to utilize novel biomarkers discov- ered by high throughput proteomic analysis to predict high PPCS. Future research should further develop precision of unique biomarker profiles and prolonged symptomatology in adolescents’ post-concussion.
2026-09-14 | PAD000053 | Pride
Project description:Introduction: Post-traumatic stress disorder (PTSD) is highly prevalent among U.S. service members and veterans (SMV) and has lasting impacts on health and well-being. However, the biological underpinnings of PTSD remain poorly characterized. This study aimed to discover novel candidate proteins and protein pathways associated with PTSD using unbiased, high-throughput proteomics profiling. Methods: A cross-sectional study was conducted using a subset of SMV participants from a clinical cohort undergoing evaluations at the National Intrepid Center of Excellence, Walter Reed National Military Medical Center, who consented to a research blood draw and use of their clinical data in research. The cohort with available blood samples was classified into PTSD-Present and PTSD-Absent groups based on the PTSD Checklist- Civilian Version. Olink high-throughput proteomic profiling examined 5400 human plasma proteins, and differentially expressed proteins were examined. Ingenuity pathway analysis was used to identify proteomic pathways among the significant differentially expressed proteins between the PTSD-Present and PTSD-Absent groups. Results: We included 208 samples in our analysis, 126 with and 82 without PTSD. We identified 366 proteins that were significantly differentially expressed between groups, with the 3 most significant being LMOD2 (Leiomodin- 2), ATP5F1D (ATP synthase δ-subunit), and CASKIN1 (CASK-interacting protein). Extracellular matrix organization pathways and Vascular Endothelial Growth Factor (VEGF) signaling were downregulated in PTSD, suggesting possible vascular inflammation and remodeling. Data- driven protein networks suggest reduced immune cell activation. Discussion: Determining differential protein expression and identifying the associated protein pathways linked to PTSD may provide new insights into the biological basis of chronic PTSD symptoms and help identify novel candidate protein biomarkers of PTSD and PTSD symptoms for validation in separate and larger cohorts. From this discovery cohort, we report that elevated PTSD symptoms may be associated with downregulation of extracellular matrix organization, inflammation signaling, and vascular remodeling pathways. Future research is necessary to validate this novel group of biomarkers and pathways.
2026-09-02 | PAD000055 | Pride
Project description:The biodegradation of lignocellulose requires the disruption of its lignin, which shields the metabolically assimilable polysaccharides in this recalcitrant natural composite. Although a variety of microorganisms can attack lignocellulose, white rot basidiomycetes are uniquely efficient at this process, cleaving the recalcitrant intermonomer linkages of lignin via extracellular oxidative mechanisms and mineralizing many of the resulting fragments to carbon dioxide via intracellular processes. Considerable progress has been made in understanding this process in the model white rot fungus Phanerochaete chrysosporium, which expresses important components of its ligninolytic system in response to nutrient limitation, as part of its secondary metabolism. Biochemical and genetic evidence point to an important role in P. chrysosporium for secreted lignin peroxidases (LiPs), manganese peroxidases (MnPs), and H2O2-producing oxidases, which are thought to work together to cleave lignin into low molecular weight fragments. However, many aspects of ligninolysis by P. chrysosporium remain poorly understood. Although a definitive picture of the entire ligninolytic system in P. chrysosporium is not yet attainable, transcriptome analyses of the fungus grown on wood can provide useful clues. With the advent of the initial genome assembly and annotations (v1.0 and v2.1), microarray-based transcriptome analysis allowed examination of transcript levels of P. chrysosporium genes when grown in ball-milled wood and in defined growth media. This approach provided useful insights but was limited to 10048 v2.1 targets and complicated by the unpredictable manner in which the fungus responds to unnatural carbon sources in submerged basal salts media. A complete, fully coordinated ligninolytic system is likely not expressed by P. chrysosporium on ball-milled wood, because a potential route for regulatory feedback has been eliminated: the cellulose and hemicellulose in this substrate is readily accessible to enzymes, and thus ligninolysis is not essential for growth. An alternative approach is to compare levels of gene expression just before and after the onset of secondary metabolism and extracellular substrate oxidation by P. chrysosporium as it utilizes solid wood as its carbon source. If this can be done, and decay of the substrate is also confirmed, then the genes undergoing marked changes in expression during the metabolic transition can be identified with greater confidence. Although not all such genes are expected to have roles in biodegradation, this strategy may identify interesting candidates for future investigation. Here we report RNAseq-based transcriptomes to characterize changes in gene expression that occur during the transition to ligninolytic metabolism. Phanerochaete chrysosporium was inoculated onto thin sections of wood. RNA was purified from colonized material after 40 and 96 hours. Single read 100 bp Illumina runs were performed.
2015-09-16 | E-GEOD-69461 | biostudies-arrayexpress
Project description:Collectively classified as white-rot fungi, certain basidiomycetes efficiently degrade the major structural polymers of wood cell walls. A small subset of these Agaricomycetes, exemplified by Phlebiopsis gigantea, is capable of colonizing freshly exposed conifer sapwood despite its high pitch content, which retards the establishment of other fungal species. The mechanism(s) by which P. gigantea tolerates and metabolizes resinous compounds have not been explored. Here, we report the annotated P. gigantea genome and compare profiles of its transcriptome and secretome when cultured on fresh-cut versus solvent-extracted loblolly pine. The P. gigantea genome contains a conventional repertoire of hydrolase genes involved in cellulose/hemicellulose degradation, whose patterns of expression were relatively unperturbed by the absence of extractives. The expression of genes typically ascribed to lignin degradation was also largely unaffected. In contrast, genes likely involved in the transformation and detoxification of pitch were highly induced in its presence. Their products included an ABC transporter, lipases, cytochrome P450s, glutathione S-transferase and aldehyde dehydrogenase. Other regulated genes of unknown function and several constitutively expressed genes are also likely involved in P. gigantea’s pitch metabolism. These results contribute to our fundamental understanding of conifer colonization and carbon cycling processes. Phlebiopsis gigantea was cultivated in media containing one of three carbon sources: freshly harvested loblolly pine (3 replicates), acetone extracted lobollly pine (3 replicates), or glucose (2 replicates). RNA was extracted and processed for Illumina sequencing as described below.
2014-10-01 | E-GEOD-53112 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2015-04-01 | E-GEOD-59572 | biostudies-arrayexpress
Project description:By using NGS-derived retinal transcriptome profiling (RNA-seq) to compare the gene expression profiling between 4 differently treated NPC cells Examination of different gene expression in EBV-miRNA-BART1/3/7 lentivirus and their control infected nasopharyngeal carcinoma cells.
2015-06-30 | E-GEOD-43126 | biostudies-arrayexpress
Project description:The active vitamin A derivative retinoic acid (RA) is an important regulator of adult brain functions. How these regulations are achieved is poorly known, partly due to the paucity of information on RA molecular targets. The striatum, the region involved in control of motor, cognitive and affective functions, may be particularly prone to such regulation as it displays the highest levels of RA and its receptors (RARs). We report the first genome-wide analysis of RAR-binding sites in the brain. Using chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq), as well as transcriptomic analysis of RARβ-null mutant mice, we identified genomic transcriptional targets of RARβ in the striatum. Our data point to a strong contribution of RARβ in controlling neurotransmission, energy metabolism, and transcription, with a particular involvement of G-protein, cAMP and calcium signaling. Quantitative PCR analysis of striatal subregions revealed a higher sensitivity of ventral structures (nucleus accumbens) to lack of RARβ signaling. There is a high overlap of transcriptional targets of RARβ and genes affected in expression in Huntingtonâs disease (HD), and we observed a decrease of RARβ expression in the striatum of R6/2 transgenic mice, a murine model of HD. A large number of genes bearing RARβ binding sites have also been implicated in Alzheimerâs and Parkinsonâs diseases, raising the possibility that compromised RA signaling in striatum may be a mechanistic link explaining the similar affective and cognitive symptoms of these diseases. Globally, our data point to a possibility of a neuroprotective function of RARβ in the striatum. Genome-wide mapping of RARβ and H3K4me3 binding sites in mouse caudate putamen
2016-07-22 | E-GEOD-67829 | biostudies-arrayexpress