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Gilbert S Omenn

Publications and source records attributed to Gilbert S Omenn.

At least 19 recordsLinked to original sources
PubMed2026

Unlocking the Circulating Proteome: Toward Clinical Translation.

Blood-based proteomics is approaching a translational inflection point. Driven by advances in measurement technologies, rapid expansion of analytical capabilities, and growing adoption across research and medical communities, there is increasing demand for clinically actionable biomarkers. As the field transitions away from purely large-scale discovery-oriented studies toward more informed, targeted, application-driven analyses, the generation of proteomic data is no longer the bottleneck. Instead, the central challenge is to translate these measurements into robust, reproducible, and clinically meaningful insights. In this Review, we assess recent technological and methodological developments, evaluate persistent preanalytical and interpretative limitations, and outline the key steps required for clinical translation. We focus on three deeply interconnected dimensions: the capabilities and constraints of current measurement platforms, the role of computational and machine learning approaches in extracting biological and clinical signals, and the emergence of large-scale population studies that create new opportunities for validation and generalization. Finally, we discuss a forward-looking vision in which proteomics plays a central role in dynamic, multilayered omics frameworks, where integration with genomics, temporal profiling, and imaging can deepen our understanding of health, disease, and therapeutic response.

Humans↗
PubMed2026

AI proteomics: from protein identification to virtual cells.

Artificial intelligence (AI) is transforming scientific research, including proteomics. In this Perspective, we highlight key mass spectrometry (MS)-based proteomics areas where AI is driving innovation, ranging from protein identification to building AI virtual cells. These include improving peptide and protein identification and quantification; characterizing protein-protein interactions and protein complexes; advancing spatial and perturbation proteomics; integrating multi-omics data; and, ultimately, enabling AI virtual cells. Finally, we call for global collaboration among data producers, data consumers and other stakeholders to establish an AI-friendly ecosystem for MS-based proteomics, laying the foundation for transformative advancements in proteomics driven by AI.

Proteomics↗
PubMed2006

Standards for plasma and serum proteomics in early cancer detection: a needs assessment report from the national institute of standards and technology--National Cancer Institute Standards, Methods, Assays, Reagents and Technologies Workshop, August 18-19, 2005.

NIST and the National Cancer Institute cosponsored a workshop on August 18-19, 2005, to examine needs for reference materials for early cancer detection. This meeting focused on standards, methods, assays, reagents, and technologies. Needs for plasma and serum proteomics, DNA methylation, and specimen reference collections were discussed, and recommendations from participants were solicited. This report summarizes the discussion and recommendations for proteomics reference materials.

Biomarkers, Tumor↗
PubMed2006

Novel gene and gene model detection using a whole genome open reading frame analysis in proteomics.

BACKGROUND: Defining the location of genes and the precise nature of gene products remains a fundamental challenge in genome annotation. Interrogating tandem mass spectrometry data using genomic sequence provides an unbiased method to identify novel translation products. A six-frame translation of the entire human genome was used as the query database to search for novel blood proteins in the data from the Human Proteome Organization Plasma Proteome Project. Because this target database is orders of magnitude larger than the databases traditionally employed in tandem mass spectra analysis, careful attention to significance testing is required. Confidence of identification is assessed using our previously described Poisson statistic, which estimates the significance of multi-peptide identifications incorporating the length of the matching sequence, number of spectra searched and size of the target sequence database. RESULTS: Applying a false discovery rate threshold of 0.05, we identified 282 significant open reading frames, each containing two or more peptide matches. There were 627 novel peptides associated with these open reading frames that mapped to a unique genomic coordinate placed within the start/stop points of previously annotated genes. These peptides matched 1,110 distinct tandem MS spectra. Peptides fell into four categories based upon where their genomic coordinates placed them relative to annotated exons within the parent gene. CONCLUSION: This work provides evidence for novel alternative splice variants in many previously annotated genes. These findings suggest that annotation of the genome is not yet complete and that proteomics has the potential to further add to our understanding of gene structures.

Alternative Splicing↗
PubMed2006

The HUPO Plasma Proteome Project: a report from the Munich congress.

The Human Proteome Organization has several major collaborative research initiatives, including the Plasma Proteome Project. A major feature of the HUPO World Congress in Munich in August 2005 was the release of the special issue of PROTEOMICS with 28 articles from the pilot phase of the Plasma Proteome Project. An open Workshop and a presentation in the closing plenary session of the congress focused on next phases for the Plasma Proteome Project.

Antibodies↗
PubMed2006

Strategies for plasma proteomic profiling of cancers.

Despite a voluminous literature on potential protein biomarkers and a compelling need for diagnostic tests based on biomarkers to detect cancers at much earlier, more treatable stages, progress has been limited. New methods and new instruments for analysis of differences in gene expression, gene methylation, and proteomics are being employed to try to accelerate the discovery phase. Given the heterogeneity of tumor mechanisms and the limitations of analytical methods, it is likely that a variety of strategies will be needed and will be complementary. That is the basis of this review of proteomic approaches. This article adopts a systems biology view, starting with mRNA transcripts in tumors and cultured tumor cells to detect mRNA overexpression, some of which will be correlated with protein overexpression. Some of those proteins may be secreted or released into proximal biofluids and plasma. Detection of low-abundance tumor proteins in the complex and dynamic mixture that is plasma requires combinations of increasingly powerful technologies. The biological amplification of protein signals through the immune system offers autoantibodies as potential biomarkers. Higher abundance proteins, including acute-phase reactants, may have practical value, especially if the proteins are modified as part of the cancer processes. Low molecular weight proteins, fragments, and peptides may offer complementary biomarkers. Promising biomarker candidates must be confirmed in independent studies. Then they must be submitted to higher-throughput methods practical for large-scale validation studies and, hopefully, for clinical and epidemiological applications. Standardized operating procedures for specimen handling, design and use of various reference standards, care to avoid bias and confounding, and guidelines for reporting findings and contributing datasets should enhance the prospects for predictive proteomic profiling of people at risk for cancers.

Biomarkers, Tumor↗
PubMed2006

Differential protein expression profiling by iTRAQ-2DLC-MS/MS of lung cancer cells undergoing epithelial-mesenchymal transition reveals a migratory/invasive phenotype.

Transforming growth factor-beta (TGF-beta) induces epithelial-mesenchymal transition (EMT) of epithelial cells in both normal embryonic development and certain pathological contexts. Here, we show that TGF-beta induced-EMT in human lung cancer cells (A549; adenocarcinoma cells) mediates tumor cell migration and invasion phenotypes. To gain insights into molecular events during EMT, we employed a global stable isotope labeled profiling strategy using iTRAQ reagents, followed by 2DLC-MS/MS, which identified a total of 51 differentially expressed proteins during EMT; 29 proteins were up-regulated and 22 proteins were down-regulated. Down-regulated proteins were predominantly enzymes involved in regulating nutrient or drug metabolism. The majority of the TGF-beta-induced proteins (such as tropomyosins, filamin A, B, & C, integrin-beta1, heat shock protein27, transglutaminase2, cofilin, 14-3-3 zeta, ezrin-radixin-moesin) are involved in the regulation of cell migration, adhesion and invasion, suggesting the acquisition of a invasive phenotype.

Adenocarcinoma↗
PubMed2006

Challenges in deriving high-confidence protein identifications from data gathered by a HUPO plasma proteome collaborative study.

The Human Proteome Organization (HUPO) recently completed the first large-scale collaborative study to characterize the human serum and plasma proteomes. The study was carried out in different locations and used diverse methods and instruments to compare and integrate tandem mass spectrometry (MS/MS) data on aliquots of pooled serum and plasma from healthy subjects. Liquid chromatography (LC)-MS/MS data sets from 18 laboratories were matched to the International Protein Index database, and an initial integration exercise resulted in 9,504 proteins identified with one or more peptides, and 3,020 proteins identified with two or more peptides. This article uses a rigorous statistical approach to take into account the length of coding regions in genes, and multiple hypothesis-testing techniques. On this basis, we now present a reduced set of 889 proteins identified with a confidence level of at least 95%. We also discuss the importance of such an integrated analysis in providing an accurate representation of a proteome as well as the value such data sets contain for the high-confidence identification of protein matches to novel exons, some of which may be localized in alternatively spliced forms of known plasma proteins and some in previously nonannotated gene sequences.

Blood Proteins↗
PubMed2005

Evidence for excess colorectal cancer incidence among asbestos-exposed men in the Beta-Carotene and Retinol Efficacy Trial.

The relation between asbestos exposure and colorectal cancer remains controversial. The authors of this 1984-2004 US study examined the association among 3,897 occupationally exposed participants in the Beta-Carotene and Retinol Efficacy Trial (CARET) for chemoprevention of lung cancer, followed prospectively for 10-18 years. When a Cox stratified proportional hazards model was used, risks of colorectal cancer were elevated among male heavy smokers exposed to asbestos. Their relative risk was 1.36 (95% confidence interval: 0.96, 1.93) when compared with that for CARET heavy smokers not exposed to asbestos, after adjusting for age, smoking history, and intervention arm. The presence of asbestos-induced pleural plaques at baseline was associated with a relative risk of 1.54 (95% confidence interval: 0.99, 2.40); colorectal cancer risk also increased with worsening pulmonary asbestosis (p = 0.03 for trend). A dose-response trend based on years of asbestos exposure was less evident. Nonetheless, these data suggest that colorectal cancer risk is elevated among men occupationally exposed to asbestos, especially those with evidence of nonmalignant asbestos-associated radiographic changes.

Adult↗
PubMed2005

Distinctive serum protein profiles involving abundant proteins in lung cancer patients based upon antibody microarray analysis.

BACKGROUND: Cancer serum protein profiling by mass spectrometry has uncovered mass profiles that are potentially diagnostic for several common types of cancer. However, direct mass spectrometric profiling has a limited dynamic range and difficulties in providing the identification of the distinctive proteins. We hypothesized that distinctive profiles may result from the differential expression of relatively abundant serum proteins associated with the host response. METHODS: Eighty-four antibodies, targeting a wide range of serum proteins, were spotted onto nitrocellulose-coated microscope slides. The abundances of the corresponding proteins were measured in 80 serum samples, from 24 newly diagnosed subjects with lung cancer, 24 healthy controls, and 32 subjects with chronic obstructive pulmonary disease (COPD). Two-color rolling-circle amplification was used to measure protein abundance. RESULTS: Seven of the 84 antibodies gave a significant difference (p < 0.01) for the lung cancer patients as compared to healthy controls, as well as compared to COPD patients. Proteins that exhibited higher abundances in the lung cancer samples relative to the control samples included C-reactive protein (CRP; a 13.3 fold increase), serum amyloid A (SAA; a 2.0 fold increase), mucin 1 and alpha-1-antitrypsin (1.4 fold increases). The increased expression levels of CRP and SAA were validated by Western blot analysis. Leave-one-out cross-validation was used to construct Diagonal Linear Discriminant Analysis (DLDA) classifiers. At a cutoff where all 56 of the non-tumor samples were correctly classified, 15/24 lung tumor patient sera were correctly classified. CONCLUSION: Our results suggest that a distinctive serum protein profile involving abundant proteins may be observed in lung cancer patients relative to healthy subjects or patients with chronic disease and may have utility as part of strategies for detecting lung cancer.

Antibodies↗
PubMed2005

Intact-protein-based high-resolution three-dimensional quantitative analysis system for proteome profiling of biological fluids.

The substantial complexity and vast dynamic range of protein abundance in biological fluids, notably serum and plasma, present a formidable challenge for comprehensive protein analysis. Integration of multiple technologies is required to achieve high-resolution and high-sensitivity proteomics analysis of biological fluids. We have implemented an orthogonal three-dimensional intact-protein analysis system (IPAS), coupled with protein tagging and immunodepletion of abundant proteins, to quantitatively profile the human plasma proteome. Following immunodepletion, plasma proteins in each of paired samples are concentrated and labeled with a different Cy dye, before mixing. Proteins are subsequently separated in three dimensions according to their charge, hydrophobicity, and molecular mass. Differences in the abundance of resolved proteins are determined based on Cy dye ratios. We have applied this strategy to profile the plasma proteome for changes that occur with acute graft-versus-host disease (GVHD), following allogeneic bone marrow transplantation (BMT). Using capillary HPLC ESI Q-TOF MS, we identified 75 proteins in the micromolar to femtomolar range that exhibited quantitative differences between the pre- and post-GVHD samples. These proteins included serum amyloid A, apolipoproteins A-I/A-IV, and complement C3 that are well-known acute-phase reactants likely reflecting the post-BMT inflammatory state. In addition, we identified some potentially interesting immunologically relevant molecules including vitamin D-binding protein, fetuin, vitronectin, proline-rich protein 3 and 4, integrin-alpha, and leukocyte antigen CD97. IPAS provides a combination of comprehensive profiling and quantitative analysis, with a substantial dynamic range, for disease-related applications.

Adult↗
PubMed2005

Predictors of lung cancer among asbestos-exposed men in the {beta}-carotene and retinol efficacy trial.

Despite numerous published studies, debate continues regarding the risk of developing lung cancer among men exposed occupationally to asbestos, particularly those without radiographic or functional evidence of asbestosis. The beta-Carotene and Retinol Efficacy Trial (CARET), a study of vitamin supplementation for chemoprevention of lung cancer, has followed 4,060 heavily exposed US men for 9-17 years. Lung cancer incidence for 1989-2002 was analyzed using a stratified proportional hazards model. The study confirmed excessive rates of lung cancer among men with radiographic asbestosis. Comparison of study arms revealed a strong, unanticipated synergy between radiographic profusion category and the active intervention. In the large subgroup of men with normal lung parenchyma on chest radiograph at baseline, there was evidence of exposure-related lung cancer risk: Men with more than 40 years' exposure in high-risk trades had a risk approximately fivefold higher than men with 5-10 years, after adjustment for covariates. The effect in these men was independent of study intervention arm, but pleural plaques on the baseline radiograph and abnormal baseline flow rate were strong independent predictors of subsequent lung cancer. Residual confounding by subclinical asbestosis, exposure to unmeasured lung carcinogens, or differences in smoking are unlikely to explain these observations better than a carcinogenic effect of asbestos per se.

Adult↗