4D-DIA Proteomics Uncovers New Insights into Host Salivary Response Following SARS-CoV-2 Omicron Infection
Ontology highlight
ABSTRACT:
INSTRUMENT(S):
ORGANISM(S): Homo Sapiens (human)
TISSUE(S): Saliva
DISEASE(S): Covid-19
SUBMITTER: 
Iasmim Lima
LAB HEAD: Marcos Nogueira
PROVIDER: PXD054133 | Pride | 2025-01-18
REPOSITORIES: Pride
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Results_DIA-NN.rar | Other | |||
| Spectral_library.tsv.speclib | Tabular | |||
| raw.rar | Other | |||
| sample_info.txt | Txt |
Items per page: 5 1 - 4 of 4 |
Publications
4D-DIA Proteomics Uncovers New Insights into Host Salivary Response Following SARS-CoV-2 Omicron Infection.
de Lima Iasmim Lopes IL Cataldi Thais Regiani TR Brites Carlos C Labate Mônica Teresa Veneziano MTV Vaz Sara Nunes SN Deminco Felice F da Cunha Gustavo Santana GS Labate Carlos Alberto CA Eberlin Marcos Nogueira MN
Journal of proteome research 20250113 2
Since late 2021, Omicron variants have dominated the epidemiological scenario as the most successful severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sublineages, driving new and breakthrough infections globally over the past two years. In this study, we investigated for the first time the host salivary response of COVID-19 patients infected with Omicron variants (BA.1, BA.2, and BA.4/5) by using an untargeted four-dimensional data-independent acquisition (4D-DIA)-based proteomics ap ...[more]
Similar Datasets
Project description:A sensitive assay to identify biomarkers that can accurately diagnose the onset of breast cancer using non-invasively collected clinical specimens is ideal for early detection. In this study, we have conducted a prospective sample collection and retrospective blinded validation (PRoBE design) to evaluate the performance and translational utilities of salivary transcriptomic and proteomic biomarkers for the non-invasive detection of breast cancer. The Affymetrix HG U133 Plus 2.0 Array and 2D-DIGE were used to profile transcriptomes and proteomes in saliva supernatants respectively. Significant variations of salivary transcriptomic and proteomic profiles were observed between breast cancer patients and healthy controls. Eleven transcriptomic biomarker candidates and two proteomic biomarker candidates were selected for a preclinical validation using an independent sample set. Transcriptomic biomarkers were validated by RT-qPCR and proteomic biomarkers were validated by quantitative protein immunoblot. Eight mRNA biomarkers and one protein biomarker have been validated for breast cancer detection, yielding ROC-plot AUC values between 0.665 and 0.959. This report provides proof of concept of salivary biomarkers for the non-invasive detection of breast cancer. The salivary biomarkersâ discriminatory power paves the way for a PRoBE-design definitive validation study. Keywords: Salivary biomarker, Breast cancer, Early detection, Salivary transcriptome, Salivary proteome This study, which was approved by the UCLA and Cedars-Sinai Medical Center Institutional Review Boards (#06-07-043 and #3870, respectively), started sample collection in February 2007. The sample collection followed the PRoBE principle (prospective specimen collection). The saliva bank for breast cancer project at the UCLA Dental Research Institute in collaboration with Cedars Sinai Medical Center has collected 200 saliva samples since 2007 with all subjects recruited from the Saul and Joyce Brandman Breast Cancer Center. Of these, 113 samples, including 41 breast cancer patients and 72 healthy control individuals, were selected for the discovery and validation phase of this study. Inclusion criteria of cancer patients consisted of a confirmed diagnosis of breast cancer. Exclusion criteria of cancer patients included therapy/surgery and/or a diagnosis of other malignancies within 5 years prior to saliva collection. Exclusion criteria of control patients included a diagnosis of any malignancies within 5 years prior to saliva collection. Written informed consents and questionnaire data sheets were obtained from all patients who agreed to serve as saliva donors. Unstimulated saliva samples were consistently collected, stabilized, and preserved as previously described. The sample supernatants were reserved at -80 C prior to assay. This study consisted of a discovery phase, followed by an independent preclinical validation phase. Of the 113 samples, 10 breast cancer samples and 10 healthy control samples were chosen for the discovery phase. All breast cancer cases are invasive ductal carcinoma (IDC), the most common type of breast cancer. Biomarkers identified from the discovery studies were first verified using the discovery sample set. An independent sample set, including 31 breast cancer patients and 62 healthy control subjects, was used for the biomarker validation phase.
2010-02-21 | E-GEOD-20266 | biostudies-arrayexpress
Project description:Pancreatic cancer is the fourth leading cause of cancer death. Lack of early detection technology for pancreatic cancer invariably leads to a typical clinical presentation of incurable disease at initial diagnosis. Oral fluid (saliva) meets the demand for non-invasive, accessible, and highly efficient diagnostic medium. The level of salivary analytes, such as mRNA and microflora, vary upon disease onset; thus possess valuable signatures for early detection and screening. In this study, we evaluated the performance and translational utilities of the salivary transcriptomic and microbial biomarkers for non-invasive detection of early pancreatic cancer. Two biomarker discovery technologies were used to profile transcriptome in saliva supernatant and microflora in saliva pellet. The Affymetrix Human Genome U133 Plus 2.0 Array was used to discover altered gene expression in saliva supernatant. The Human Oral Microbe Identification Microarray (HOMIM) was used to investigate microflora shift in saliva pellet. Biomarkers selected from both studies were subjected to an independent clinical validation using a cohort of 30 early pancreatic cancer, 30 chronic pancreatitis and 30 healthy matched-control saliva samples. Two panels of salivary biomarkers, including eleven mRNA biomarkers and two microbial biomarkers were discovered and validated for pancreatic cancer detection. The logistic regression model with the combination of three mRNA biomarkers (ACRV1, DMXL2 and DPM1) yielded a ROC-plot AUC value of 0.974 (95% CI, 0.896 to 0.997; P < 0.0001) with 93.3% sensitivity and 90% specificity in distinguishing pancreatic cancer patients from healthy subjects. The logistic regression model with the combination of two bacterial biomarkers (Neisseria elongata and Streptococcus mitis) yielded a ROC-plot AUC value of 0.895 (95% CI, 0.784 to 0.961; P < 0.0001) with 96.4% sensitivity and 82.1% specificity in distinguishing pancreatic cancer patients from healthy subjects. Importantly, the logistic regression model with the combination of four biomarkers (mRNA biomarkers, ACRV1, DMXL2 and DPM1; bacterial biomarker, S. mitis) could differentiate pancreatic cancer patients from all non-cancer subjects (chronic pancreatitis and healthy control), yielding a ROC-plot AUC value of 0.949 (95% CI, 0.877 to 0.985; P < 0.0001) with 92.9% sensitivity and 85.5% specificity. This study comprehensively compared the salivary transcriptome and microflora between pancreatic cancer and control subjects. We have discovered and validated eleven mRNA biomarkers and two microbial biomarkers for early detection of pancreatic cancer in saliva. The logistic regression model with four salivary biomarkers can detect pancreatic cancer specifically without the complication of chronic pancreatitis. This is the first report demonstrating the value of multiplex salivary biomarkers for the non-invasive detection of a high impact systemic cancer. Keywords: Salivary biomarker, pancreatic cancer, early detection, salivary transcriptome, salivary microflora This study, which was approved by the UCLA Institutional Review Board, started sample collection in February 2006 and ended in April 2008. It had a discovery and verification phase, followed by an independent validation phase. All patients with clinically diagnosed early or locally advanced pancreatic cancer, chronic pancreatitis and matched healthy control were recruited from the UCLA Medical Center. The controls were matched for gender, age, ethnicity and smoking history. We chose early and locally advanced pancreatic cancers because they were considered early stage diseases. All patients were recently diagnosed with primary disease, and had not received any prior treatment in the form of chemotherapy, radiotherapy, surgery, or alternative remedies. No subjects had a history of prior malignancy, immunodeficiency, autoimmune disorders, hepatitis, or HIV infection. Written informed consent was obtained from all patients who agreed to serve as saliva donors. Unstimulated saliva samples were collected and processed as previously described. The saliva bank of pancreatic disease at the UCLA Dental Research Institute has collected 283 saliva samples since 2006. Of these, 114 samples, from 42 pancreatic cancer patients, 30 chronic pancreatitis patients and 42 healthy control subjects, met the following eligibility criteria: the disease subjectsâ?? samples were obtained immediately after primary diagnosis from patients without evidence of metastasis; the saliva sample was free of blood (Table 1 in accompanying manuscript). Of the 114 samples, 12 pancreatic cancer samples and 12 healthy control samples were chosen for the discovery and verification phase. The transcriptomic approach profiled the saliva supernatant samples from 12 pancreatic cancer patients and 12 healthy control subjects using the Affymetrix Human Genome U133 Plus 2.0 Array platform.
2008-12-30 | E-GEOD-14245 | biostudies-arrayexpress
Project description:dia-PASEF analysis of human amygdala in Alzheimer’s disease
2023-06-28 | PXD038322 | Pride
Project description:dia-PASEF analysis of human amygdala in Parkinson’s disease
2024-01-26 | PXD043503 | Pride
Project description:Activity-based protein profiling (ABPP) uses a combination of activity-based chemical probes with mass spectrometry (MS) to selectively characterise a particular enzyme or enzyme class. ABPP has proven invaluable for profiling enzymatic inhibitors in drug discovery. When applied to cell extracts and cells, challenging the ABP-enzyme complex formation with a small molecule can simultaneously inform on potency, selectivity, reversibility/binding affinity, permeability, and stability. ABPP can also be applied to pharmacodynamic studies to inform on cellular target engagement within specific organs when applied to in vivo models. Recently, we established separate high depth and high throughput ABPP (ABPP-HT) protocols for the profiling of deubiquitylating enzymes (DUBs). However, the combination of the two, deep and fast, in one method has been elusive. To further increase the sensitivity of the current ABPP-HT workflow we implemented state-of-the-art data-independent acquisition (DIA) and data-dependent acquisition (DDA) MS analysis tools. Hereby, we describe an improved methodology, ABPP-HT* (enhanced high-throughput-compatible activity-based protein profiling), that in combination with DIA MS methods allowed for the consistent profiling of 35-40 DUBs and provided a reduced number of missing values, whilst maintaining a throughput of 100 samples per day.
2022-04-04 | PXD031848 | Pride
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:Affymetrix HG U133 Plus 2.0 Array (Affymetrix, Santa Clara, CA) was used to profile transcriptomes and discover altered gene expression in saliva supernatant. Salivary transcriptomic biomarker discovery was performed on 10 lung cancer patients and 10 matched controls. Seven messenger RNA biomarkers were discovered and pre-validated This study consisted of two phases, including a discovery phase, followed by a pre-validation phase. 10 lung cancer samples and 10 matched control samples were chosen for the biomarker discovery phase. The transscriptomic approach profiled the saliva supernatant samples from 10 lung cancer patients and 10 healthy control subjects using the Affymetrix HG U133 Plus 2.0 Array (Affymetrix, Santa Clara, CA). Biomarkers identified from the microarray study were first verified using the discovery sample set (10 lung cancer and 10 healthy control).
2013-01-11 | E-GEOD-32175 | biostudies-arrayexpress
Project description:This study aimed to compare the proteomic profile of stimulated and unstimulated saliva sam-ples from pregnant women with/without obesity and periodontitis. Initially, 126 pregnant women were recruited and, after exclusions, were allocated into: with obesity and periodontitis (OP); with obesity but without periodontitis (OWP); with normal BMI but with periodontitis (NP); with normal BMI and without periodontitis (NWP). Stimulated saliva (SS) and unstimulated saliva (US) samples were collected, and salivary proteins were extracted and individually processed by proteomic analysis (nLC-ESI-MS/MS). Proteins involved with immune response process, antiox-idant activity, and retina homeostasis were decreased or absent in SS samples from all groups (i.e., Antileukoproteinase, Lysozyme C, Alpha-2-macroglobulin-like protein 1, Heat shock proteins – 70kDa 1-like, 1A, 1B, 6, Heat shock-related 70 kDa protein 2, Putative Heat shock 70 kDa protein 7, Heat shock cognate 71 kDa). Also, proteins related to carbohydrate metabolic process and gly-colytic and glucose metabolic process were absent in SS, mainly from OP and OWP (i.e., Fru-tose-bisphosphate aldose A, Glusoce-6-phosphate isomerase, Pyruvate kinase). Saliva stimulation decreased important proteins involved with immune response and inflammation process in all groups. Unstimulated salivary samples seem to be the best choice to proteomic approach in pregnant women.
2023-10-24 | PXD040373 | Pride
Project description:Background and Aims: Colorectal adenomas (CRAs) are precursor lesions that can progress to adenocarcinomas. Current clinical guidelines categorize patients into risk groups based on adenoma characteristics observed during index colonoscopy, but this may lead to overtreatment. Our aim was to establish a molecular feature-based risk allocation framework towards improved patient stratification. Methods: Deep Visual Proteomics (DVP) is a novel approach that combines image-based artificial intelligence with automated microdissection and ultra-high sensitive mass spectrometry. Here we used DVP on formalin-fixed, paraffin-embedded (FFPE) CRA tissues from nine patients. Immunohistological staining for Caudal-type homeobox 2 (CDX2), a gene implicated in colorectal cancer, enabled the characterization of cellular heterogeneity within distinct tissue regions and across patients. Results: DVP seamlessly integrated with current pathology workflows and equipment, identifying deleted in malignant brain tumors 1 (DMBT1), myristoylated alanine rich protein kinase C (MARCKS), and cluster of differentiation 99 (CD99) correlated with disease recurrence history, making them potential markers of risk stratification. The spatial and cell type specific capabilities of DVP uncovered a metabolic switch towards anaerobic glycolysis in areas of high dysplasia, which was specific for the cells with high CDX2 expression. Conclusion: The application of spatially resolved proteomics to CRA revealed three new potential markers for early-stage tumor development, and provided novel insights into metabolic reprogramming. Our findings underscore the potential of this technology to refine early-stage detection and contribute to personalized patient management strategies.
2024-08-04 | PXD046999 | Pride
Project description:Here, we characterize the cellular and extracellular matrix proteomes of primary human coronary artery endothelial cells, from multiple donors, and oxidation/nitration products formed on these during cell culture. Liquid chromatography-mass spectrometry with or without prior fractionation, and different data acquisition methods were employed. In total ~9900 proteins were identified across 3 donors, with ~7000 proteins per donor. Of these ~5300 were consistently identified, indicating heterogeneity across the donors, with donor age a probable cause. Multiple endogenous oxidations and nitrations were detected. The former are present on both cell and ECM proteins, whilst a majority of the latter were detected on cell proteins, consistent with intracellular generation of nitrating agents, most likely from eNOS or peroxidase enzyme activity. The modifications are ascribed to both physiological enzymatic activity (hydroxylation at proline/lysine, predominantly on ECM proteins and especially collagens) and reactive species (oxidation at tryptophan/tyrosine/histidine; nitration at tryptophan/tyrosine).
2025-02-17 | PXD056929 | Pride