Profiling of differentially expressed microRNAs in saliva of Parkinson’s disease patients
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Yanyan Jiang
PROVIDER: E-MTAB-10779 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Ovarian cancer is the leading cause of death in gynecological diseases, and has been considered as one of the most fatal cancers due to lack of reliable detection strategy in the early stage. Therefore the capability to detect the morbidity initiation with an sensitive and effective approach is one of the most desirable goals for curing ovarian cancer. In this study, we used microarray technology for salivary mRNA biomarkers discovery, and evaluated the performance and translational utilities of discovered markers from a clinical study using an independent sample cohort . We used microarrays to profile and compare the gene expressions between ovairan cancer patient and matched controls, and identified seven down-regulated genes after the validation study. To find salivary transcriptomic biomarkers for ovarian cancer, salivary transcriptomes in 11 ovarian cancer patients and 11 matched controls were profiled using Affymetrix HG-U133-Plus-2.0 array, and followed by t-test and fold-change analyses. The biomarker candidates selected from the microarray results were subjected to clinical validation using an independent sample cohort by RT-qPCR. The prediction power of biomarkers was analyzed by logistic regression approach
2011-05-12 | E-GEOD-29220 | biostudies-arrayexpress
Project description:Salivary proteins of mouth breathing children were compared with paired nose breathing children using label-free quantification (LFQ). The differentially expressed proteins were screened (fold-change 1.5, p value<0.05).
2021-09-09 | PXD021106 | Pride
Project description:The oral cavity is home to one of the most diverse microbial community of the human body and a major entry portal for pathogens. Its homeostasis is maintained by saliva, which fulfills key functions including lubrication of food, predigesting and bacterial defense. Consequently, disruptions in saliva secretion contributes to conditions such as tooth decay and respiratory tract infections. Here we used recent improvements in mass spectrometry (MS)-based proteomics to develop a rapid workflow for mapping to map the saliva proteome quantitatively and at great depth. Microgram protein amounts retrieved from cotton swabs were processed in a single-run format, resulting in more than 3,700 quantified human proteins in 100 min measurements gradients. After separation into eight fractions, this increased to 5,500 human proteins. Remarkably, our measurements also quantified more than 2,000 microbial proteins and we find peptide evidence for more than 70 bacterial genera without any microbial culture. Co-analysis of the proteomics results with next generation sequencing data as well as MALDI Biotyper revealed strong agreement. The oral microbiome differs between individuals and changes drastically upon eating and tooth brushing. Rapid and robust shotgun technology can now simultaneously characterize the human and microbiome contributions to the proteome of a body fluid.
2016-03-18 | PXD003028 | Pride
Project description:Exosomes are molecular entities derived from membrane vesicles of endocytic origin secreted by most cell types. These vesicles are implicated in cell-to-cell communication, deliver proteins and mRNA molecules between cells. Recent studies have shown that exosomes are found in body fluids such as saliva, blood, urine, amniotic fluid, malignant ascites, bronchoalveolar lavage fluid, synovial fluids and breast milk. Exosomes secreted through human saliva contain mRNA may potentially be useful for diagnostic purposes. Although the exact protective mechanism of saliva RNA is a topic of debate, the consensus is that the enrichment of mRNAs in these nano-vesicles in one of the features of the biomarker discoveries. Our aim was to determine if exosomes are present in human saliva and to nano-characterize their transcriptomic content. Exosomes were purified by differential ultracentrifugation, identified by immunoelectron microscopy, flow cytometry and western blot using a CD-63 antibody. Atomic force microscopy studies revealed ultra structural analysis of both size and density of exosomes. Microarray analysis revealed the presence of 590 mRNA core transcripts are relatively stable inside the exosomes, which can be of saliva mRNA biomarkers. Exosomal mRNA stability was determined by detergent lyses with treatment of RNase. Under in vitro conditions fluorescent dye labeled saliva exosomes were able to communicate between human oral keratinocytes studied by using fluorescence microscopy. The RNA from saliva exosomes can transfer their genetic information to human oral keratinocytes and alters gene expression in the new location. Together, these results suggest that saliva is involved in mRNA trafficking via exosomes, and provides a mechanism for cargoing passenger mRNAs. Our findings are consistent with proposal that exosomes can shuttle RNAs between cells and mRNA is protected inside these vesicles may be a possible resource for biomarker discovery. Experiment Overall Design: Human saliva exosomes were purified through differential centrifugation followed by RNA extraction and hybridization on Affymetrix microarrays. We were able to obtain normal human subjects saliva which are pooled and subjected to ultracentrifugation. The protocol was approved by UCLA Institutional review board. 1 ml of saliva exosomes were used to extract RNA followed by two rounds of amplification by Actorus Amp kit. The amplified RNA was biotin labled and hybridized with Affymetrix protocol.
2008-11-15 | E-GEOD-13494 | biostudies-arrayexpress
Project description:In orthodontic therapy periodontal tissue responds to mechanical stimuli by bone remodeling mediated by specific molecules involved in periodontal regeneration and homeostasis. The resulting changes are reflected in the salivary proteome that is emerging as a valuable diagnostic tool. We analyzed the changes of saliva proteome during orthodontic tooth movement in 12 healthy male patients, presented with malocclusion treated by placement of fixed orthodontic appliance. Six patients with identical dental pathology, but no orthodontic therapy were used as control samples. Saliva was collected a day before, immediately after, and 2, 7 and 30 days after the placement of the fixed orthodontic appliance and analyzed by LC-MS. Total of 198 proteins were identified and classified on the basis of their functional characteristics. Proteins involved in bone remodeling, inflammation and healing were detected mostly 30 days after placement of the fixed orthodontic appliance. At this time point, Bone morphogenetic protein 4 emerged as a central player in the ongoing dental bone remodeling. Besides BMP4, BMP antagonists: BMP Binding Endothelial Regulator (BMPER), Insulin-like growth factor-binding protein 3 (IGFBP3), Cytoskeleton-associated protein 4 (CKAP4) and Fibroblast growth factor 5 (FGF5), were also identified. Presence of BMP4 in human saliva 30 days after the placement of orthodontic fixed appliance was confirmed by ELISA and concentration of BMP4 was 3.2 pg/ml. To date, there is no published data on the presence of BMP molecules or their antagonists in saliva or the gingival cervical fluid, regardless of different orthodontic treatments or disease. BMP4 is involved not only in orthodontic treatment, but also in processes involving tooth development and homeostasis. Therefore, a better understanding of its networks in bone remodeling during OTM is heralded.
2021-09-09 | PXD016481 | Pride
Project description:Background: Low birth weight is associated with an increased adult metabolic disease risk. It is widely discussed that poor intrauterine conditions could induce long-lasting epigenetic modifications, leading to systemic changes in regulation of metabolic genes. In a unique cohort of 17 monozygotic (MZ) monochorionic female twins very discordant for birth weight (relative differences ranging from 21.3-35.7%), we examined if adverse prenatal growth conditions experienced by the smaller co-twins lead to systemic long-lasting DNA methylation changes. Genome-wide DNA methylation profiles were acquired from saliva DNA using the Infinium HumanMethylation450 BeadChip, targeting ~2% of all CpGs in the genome. Results: Overall, co-twins showed very similar genome-wide DNA methylation profiles. Since observed differences were almost exclusively caused by variable cellular composition, an original marker-based adjustment strategy was developed to eliminate such variation at affected CpGs. Among adjusted and unchanged CpGs 3153 were differentially methylated between the heavy and light co-twins at nominal significance (p<0.01), of which 45 showed absolute mean β-value differences >0.05 (max=0.08). Deep bisulfite sequencing of eight such loci revealed that differences remained in the range of technical variation, arguing against a reproducible biological effect. Analysis of methylation in repetitive elements using methylation-dependent primer extension assays also indicated no significant intra-pair differences. Conclusions: Severe intrauterine growth differences observed within these MZ twins are not associated with long-lasting DNA methylation differences in cells composing saliva, detectable with up-to-date technologies. Additionally, our results indicate that uneven cell type composition can lead to spurious results and should be addressed in epigenomic studies. DNA methylation profiles of saliva from 17 Adult Female MZ MC Twins discordant for birth weight.
2013-05-13 | E-GEOD-39560 | biostudies-arrayexpress
Project description:Parkinson’s disease (PD) is a progressive neurodegenerative disorder. Lewy pathology involves numerous organs. Submandibular glands are affected in about 75% of in vivo cases, with higher rates of positive findings in post-mortem histopathological studies. Salivary microbiome composi-tion in PD patients is also different than in healthy patients. Therefore, we hypothesize that saliva may serve as a potential source of biomarkers of Parkinson’s disease. To evaluate and compare the salivary proteome of PD patients and healthy controls (HC). Salivary samples from 39 subjects (24 PD patients mean age 61.6 8.2 and 15 HC mean age 60.96.7) were used. Saliva was collected 30 minutes after rinsing mouth with tap water, in the morning hours, using RNA-Pro-Sal kits. Samples were immediately frozen at -80oC after collection. Label-free LC-MS/MS mass spectrometry was performed to comprehensively characterize the proteome of the saliva. IPA analysis of upstream inhibitors was performed. A total of 530 proteins and peptides were identified. We observed significantly lower concentrations of S100-A16, ARP2/3 and VPS4B in PD group vs controls. Additional IPA analysis indicated PD98059 to be most significantly activated and beta-estradiol most significantly inhibited upstream regulators. Conclusions: Very limited data on the salivary proteome of PD subjects is available. The results of our analysis indicate that the salivary proteome of PD patients might be different than that of healthy controls. We observed significantly lower concentrations of proteins involved in inflammatory processes, exosome formation and adipose tissue formation among others. Upstream regulator analysis indicated several proteins previously associated with neurodegeneration to drive the differential protein expression in saliva. The main limitations of the study are variability of expression of proteins between subjects in the two groups and variations caused by external factors.
2022-10-14 | PXD023489 | Pride
Project description:Investigation of whole genome gene expression level changes in a Tim-3 knockdown RAW264.7 cell, compared to control siRNA transfected RAW264.7 cell. The Tim-3 knockdown of this cell render it hyper-reactive to TLR stimulation. Tim-3 knockdown analyzed in this study are further described in Li Y, Feng J, Geng S, Geng S, Wei H, Chen G, Li X, Wang L, Wang R, Peng H, Han G, Shen B, Li Y. 2011. The N- and C-terminal carbohydrate recognition domains of galectin-9 contribute differently to its multiple functions in innate immunity and adaptive immunity. Mol Immunol. 48(4):670-7. (PID 21146220) A six chip study using total RNA recovered from Tim-3 knockdown and control RAW264.7 cells. There are 135,000 probes in a chip,each chip measures the expression level of 27526 genes of mouse from Nimblegen. Fold-change screening between the two groups obtained from the experiment. The threshold used to screen up or down regulated genes is Fold changeM-oM-<M-^-oM-<M-^]2.0
2012-12-05 | E-GEOD-42729 | biostudies-arrayexpress
Project description:This is a pilot study. We are trying to detect potential salivary biomarkers in mice with a pancreatic tumor. Global gene expression profiling has shown great promise in high-throughput biomarker discovery for early disease detection in body fluids such as saliva, which is accessible, cost-effective, and non-invasive. However, this goal has not been fully realized because saliva, like many clinical samples, contains partially fragmented and degraded RNAs that are difficult to amplify and detect with prevailing technologies. Here, using nanogram scale salivary RNA as a proof-of-principle example, we describe our progress with a novel poly-A tail independent mRNA amplification strategy combined with the Affymetrix GeneChip Exon arrays. We defined a Salivary Exon Core Transcriptome (SECT) with highly similar expression profiles in healthy individuals verified by quantitative PCR. Informatics analysis of SECT provided important mechanistic insight to their potential origin and function. Finally we demonstrated the diagnostic potential of true exon level expression profiling approach with salivary exon biomarkers that accurately discriminated gender in healthy individuals. Recent studies have demonstrated that discriminatory salivary biomarkers can be readily detected upon the development of systemic diseases such as pancreatic cancer, breast cancer, lung cancer and ovarian cancer. However, the utility of salivary biomarkers for the detection of systemic diseases has been undermined due to the absence of biological and mechanistic rationale why distal diseases from the oral cavity would lead to the development of discriminatory biomarkers in saliva. Here, we examine the hypothesis that pancreatic tumor-derived exosomes are mechanistically involved in the development of pancreatic cancer-discriminatory salivary transcriptomic biomarkers. We first developed a pancreatic cancer mouse model that yielded discriminatory salivary biomarkers by implanting the mouse pancreatic cancer cell line Pan02 into the pancreas of the syngeneic host C57BL/6. The role of pancreatic cancer-derived exosomes in the development of discriminatory salivary biomarkers was then tested by engineered a Pan02 cell line that is suppressed for exosome biogenesis, implanted into the C56BL/6 mouse and examine if the discriminatory salivary biomarker profile was ablated or disrupted. Suppression of exosome biogenesis results in the ablation of discriminatory salivary biomarker development. This study supports that tumor-derived exosomes provide a mechanism in the development of discriminatory biomarkers in saliva and distal systemic diseases. We analyzed saliva from 6 healthy mice and 6 mice with a pancreatic tumor using the Affymetrix Mouse Exon Genome 430 2.0 platform. Array data was processed by dChip. No techinical replicates were performed.
2013-06-12 | E-GEOD-47811 | biostudies-arrayexpress
Project description:Genome wide DNA methylation profiling of saliva DNA from 197 alcohol dependent subjects. The Illumina Infinium 27k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs in saliva samples. Bisulphite converted DNA were hybridised to the Illumina Infinium 27k Human Methylation Beadchip v1.2
2011-12-01 | E-GEOD-34035 | biostudies-arrayexpress