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Smith BJ, Guest PC, Martins-de-Souza D. Maximizing Analytical Performance in Biomolecular Discovery with LC-MS: Focus on Psychiatric Disorders. ANNUAL REVIEW OF ANALYTICAL CHEMISTRY (PALO ALTO, CALIF.) 2024; 17:25-46. [PMID: 38424029 DOI: 10.1146/annurev-anchem-061522-041154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/02/2024]
Abstract
In this review, we discuss the cutting-edge developments in mass spectrometry proteomics and metabolomics that have brought improvements for the identification of new disease-based biomarkers. A special focus is placed on psychiatric disorders, for example, schizophrenia, because they are considered to be not a single disease entity but rather a spectrum of disorders with many overlapping symptoms. This review includes descriptions of various types of commonly used mass spectrometry platforms for biomarker research, as well as complementary techniques to maximize data coverage, reduce sample heterogeneity, and work around potentially confounding factors. Finally, we summarize the different statistical methods that can be used for improving data quality to aid in reliability and interpretation of proteomics findings, as well as to enhance their translatability into clinical use and generalizability to new data sets.
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Affiliation(s)
- Bradley J Smith
- 1Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, São Paulo, Brazil;
| | - Paul C Guest
- 1Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, São Paulo, Brazil;
- 2Department of Psychiatry, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany
- 3Laboratory of Translational Psychiatry, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany
| | - Daniel Martins-de-Souza
- 1Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, São Paulo, Brazil;
- 4Experimental Medicine Research Cluster, University of Campinas, São Paulo, Brazil
- 5National Institute of Biomarkers in Neuropsychiatry, National Council for Scientific and Technological Development, São Paulo, Brazil
- 6D'Or Institute for Research and Education, São Paulo, Brazil
- 7INCT in Modelling Human Complex Diseases with 3D Platforms (Model3D), São Paulo, Brazil
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Florens N, Guebre-Egziabher F, Juillard L. Reconsidering adsorption in hemodialysis: is it just an epiphenomenon? A narrative review. J Nephrol 2021; 35:33-41. [PMID: 33837932 DOI: 10.1007/s40620-021-00993-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Accepted: 02/04/2021] [Indexed: 01/31/2023]
Abstract
Since the first attempt at extracorporeal renal replacement therapy, renal replacement therapy has been constantly improved. In the field of hemodialysis, substantial efforts have been made to improve toxin removal and biocompatibility. The advent of hemodiafiltration (HDF) and, more recently, of mid cut-off membranes have contributed to management of patients with end-stage renal disease (ESRD). Although several uremic toxins have been discovered, we know little about the clinical impact of their clearance in hemodialysis patients. In addition, a great deal of progress has been made in the areas of filtration and diffusion, but the adsorptive properties of hemodialysis membranes remain under-studied. The mechanism of action of adsorption is based on the attraction between the polymer of the dialysis membrane and the solutes, through hydrophobic interactions, ionic or electrostatic forces, hydrogen bonds or van der Waals forces. Adsorption on the dialysis membrane depends on the membrane surface, pore size, structure and electric load. Its involvement in toxin removal and biocompatibility is significant, and is not just an epiphenomenon. Diffusive and convective properties cannot be improved indefinitely and high permeability membranes, despite their high performance in the clearance of many toxins, have several limitations for long-term use in hemodialysis. This review will discuss why adsorption should be reconsidered and better characterized to improve efficiency and adequacy of dialysis.
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Affiliation(s)
- Nans Florens
- Department of Nephrology, Dialysis and Hypertension, Edouard Herriot Hospital, Hospices Civils de Lyon, 5 Place d'Arsonval, Cedex 03, 6943769003, Lyon, France. .,CarMeN, INSERM U1060, INRA U1397, INSA de Lyon, Université Claude Bernard Lyon 1, University of Lyon, 69500, Bron, France.
| | - Fitsum Guebre-Egziabher
- Department of Nephrology, Dialysis and Hypertension, Edouard Herriot Hospital, Hospices Civils de Lyon, 5 Place d'Arsonval, Cedex 03, 6943769003, Lyon, France.,CarMeN, INSERM U1060, INRA U1397, INSA de Lyon, Université Claude Bernard Lyon 1, University of Lyon, 69500, Bron, France
| | - L Juillard
- Department of Nephrology, Dialysis and Hypertension, Edouard Herriot Hospital, Hospices Civils de Lyon, 5 Place d'Arsonval, Cedex 03, 6943769003, Lyon, France.,CarMeN, INSERM U1060, INRA U1397, INSA de Lyon, Université Claude Bernard Lyon 1, University of Lyon, 69500, Bron, France
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Wu P, Tang Y, Cao G, Li J, Wang S, Chang X, Dang M, Jin H, Zheng C, Cai Z. Determination of Environmental Micro(Nano)Plastics by Matrix-Assisted Laser Desorption/Ionization–Time-of-Flight Mass Spectrometry. Anal Chem 2020; 92:14346-14356. [DOI: 10.1021/acs.analchem.0c01928] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Affiliation(s)
- Pengfei Wu
- Guangdong Provincial Key Laboratory of Soil and Groundwater Pollution Control, School of Environmental Science and Engineering, Southern University of Science and Technology, Shenzhen 518055, P. R. China
- State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong SAR 999077, P. R. China
- State Environmental Protection Key Laboratory of Integrated Surface Water-Groundwater Pollution Control, School of Environmental Science and Engineering, Southern University of Science and Technology, Shenzhen 518055, P. R. China
| | - Yuanyuan Tang
- Guangdong Provincial Key Laboratory of Soil and Groundwater Pollution Control, School of Environmental Science and Engineering, Southern University of Science and Technology, Shenzhen 518055, P. R. China
- State Environmental Protection Key Laboratory of Integrated Surface Water-Groundwater Pollution Control, School of Environmental Science and Engineering, Southern University of Science and Technology, Shenzhen 518055, P. R. China
| | - Guodong Cao
- State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong SAR 999077, P. R. China
| | - Jiangpeng Li
- Guangdong Provincial Key Laboratory of Soil and Groundwater Pollution Control, School of Environmental Science and Engineering, Southern University of Science and Technology, Shenzhen 518055, P. R. China
- State Environmental Protection Key Laboratory of Integrated Surface Water-Groundwater Pollution Control, School of Environmental Science and Engineering, Southern University of Science and Technology, Shenzhen 518055, P. R. China
| | - Siqing Wang
- Guangdong Provincial Key Laboratory of Soil and Groundwater Pollution Control, School of Environmental Science and Engineering, Southern University of Science and Technology, Shenzhen 518055, P. R. China
- State Environmental Protection Key Laboratory of Integrated Surface Water-Groundwater Pollution Control, School of Environmental Science and Engineering, Southern University of Science and Technology, Shenzhen 518055, P. R. China
| | - Xinyi Chang
- Guangdong Provincial Key Laboratory of Soil and Groundwater Pollution Control, School of Environmental Science and Engineering, Southern University of Science and Technology, Shenzhen 518055, P. R. China
- State Environmental Protection Key Laboratory of Integrated Surface Water-Groundwater Pollution Control, School of Environmental Science and Engineering, Southern University of Science and Technology, Shenzhen 518055, P. R. China
| | - Miao Dang
- Guangdong Provincial Key Laboratory of Soil and Groundwater Pollution Control, School of Environmental Science and Engineering, Southern University of Science and Technology, Shenzhen 518055, P. R. China
| | - Hangbiao Jin
- Key Laboratory of Microbial Technology for Industrial Pollution Control of Zhejiang Province, College of Environment, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, P. R. China
| | - Chunmiao Zheng
- Guangdong Provincial Key Laboratory of Soil and Groundwater Pollution Control, School of Environmental Science and Engineering, Southern University of Science and Technology, Shenzhen 518055, P. R. China
- State Environmental Protection Key Laboratory of Integrated Surface Water-Groundwater Pollution Control, School of Environmental Science and Engineering, Southern University of Science and Technology, Shenzhen 518055, P. R. China
| | - Zongwei Cai
- State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong SAR 999077, P. R. China
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Lim J, Cho J, Paik Y, Chang Y, Kim H. Diagnostic Application of Serum Proteomic Patterns in Gastric Cancer Patients by ProteinChip Surface-Enhanced Laser Desorption/Ionization Time-of-Flight Mass Spectrometry. Int J Biol Markers 2018; 22:281-6. [DOI: 10.1177/172460080702200407] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) is one of the currently used techniques to identify biomarkers for cancers. This study was planned to establish a system to accurately distinguish gastric cancer patients by using SELDI-TOF-MS. A total of 100 serum samples obtained from 60 individuals with gastric cancer and 40 healthy individuals were screened. Protein expression profiles were expressed on CM10 ProteinChip arrays and analyzed. Peak intensities were analyzed with the Biomarker Wizard software to identify peaks showing significantly different intensities between normal and cancer groups. Classification analysis and construction of decision trees were done with the Biomarker Pattern software 5.0. Seventeen protein peaks showed significant differences between the two groups. The decision tree which gave the highest discrimination included four peaks at mass 5,919, 8,583, 10,286, and 13,758 as splitters. The sensitivity and specificity for classification of the decision tree were 96.7% (58/60) and 97.5% (39/40), respectively. When the protein biomarker pattern was tested on a blinded test set, it yielded a sensitivity of 93.3% (28/30) and a specificity of 90% (18/20). These results suggest that serum protein profiling by the SELDI system may distinguish gastric cancer patients from healthy controls with relatively high sensitivity and specificity.
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Affiliation(s)
- J.Y. Lim
- Department of Internal Medicine, Yonsei Yongdong Cancer Center, Yonsei University College of Medicine, Seoul
| | - J.Y. Cho
- Department of Internal Medicine, Yonsei Yongdong Cancer Center, Yonsei University College of Medicine, Seoul
| | - Y.H. Paik
- Department of Internal Medicine, Yonsei Yongdong Cancer Center, Yonsei University College of Medicine, Seoul
| | - Y.S. Chang
- Department of Internal Medicine, Yonsei Yongdong Cancer Center, Yonsei University College of Medicine, Seoul
| | - H.G. Kim
- Department of Pathology, Yonsei University College of Medicine, Seoul - South Korea
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Laputková G, Schwartzová V, Bánovčin J, Alexovič M, Sabo J. Salivary Protein Roles in Oral Health and as Predictors of Caries Risk. Open Life Sci 2018; 13:174-200. [PMID: 33817083 PMCID: PMC7874700 DOI: 10.1515/biol-2018-0023] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2018] [Accepted: 02/13/2018] [Indexed: 12/13/2022] Open
Abstract
This work describes the current state of research on the potential relationship between protein content in human saliva and dental caries, which remains among the most common oral diseases and causes irreversible damage in the oral cavity. An understanding the whole saliva proteome in the oral cavity could serve as a prerequisite to obtaining insight into the etiology of tooth decay at early stages. To date, however, there is no comprehensive evidence showing that salivary proteins could serve as potential indicators for the early diagnosis of the risk factors causing dental caries. Therefore, proteomics indicates the promising direction of future investigations of such factors, including diagnosis and thus prevention in dental therapy.
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Affiliation(s)
- Galina Laputková
- Department of Medical and Clinical Biophysics, Faculty of Medicine, University of P. J. Šafárik in Košice, Trieda SNP 1, Košice, 040 11, Slovakia
| | - Vladimíra Schwartzová
- 1st Department of Stomatology, Faculty of Medicine, University of P. J. Šafárik in Košice, Trieda SNP 1, Košice, 040 11, Slovakia
| | - Juraj Bánovčin
- Department of Stomatology and Maxillofacial Surgery, Faculty of Medicine, University of P. J. Šafárik in Košice, Rastislavova 43, Košice, 041 90, Slovakia
| | - Michal Alexovič
- Department of Medical and Clinical Biophysics, Faculty of Medicine, University of P. J. Šafárik in Košice, Trieda SNP 1, Košice, 040 11, Slovakia
| | - Ján Sabo
- Department of Medical and Clinical Biophysics, Faculty of Medicine, University of P. J. Šafárik in Košice, Trieda SNP 1, Košice, 040 11, Slovakia
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Wetmore BA, Merrick BA. Invited Review: Toxicoproteomics: Proteomics Applied to Toxicology and Pathology. Toxicol Pathol 2016; 32:619-42. [PMID: 15580702 DOI: 10.1080/01926230490518244] [Citation(s) in RCA: 141] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Global measurement of proteins and their many attributes in tissues and biofluids defines the field of proteomics. Toxicoproteomics, as part of the larger field of toxicogenomics, seeks to identify critical proteins and pathways in biological systems that are affected by and respond to adverse chemical and environmental exposures using global protein expression technologies. Toxicoproteomics integrates 3 disciplinary areas: traditional toxicology and pathology, differential protein and gene expression analysis, and systems biology. Key topics to be reviewed are the evolution of proteomics, proteomic technology platforms and their capabilities with exemplary studies from biology and medicine, a review of over 50 recent studies applying proteomic analysis to toxicological research, and the recent development of databases designed to integrate -Omics technologies with toxicology and pathology. Proteomics is examined for its potential in discovery of new biomarkers and toxicity signatures, in mapping serum, plasma, and other biofluid proteomes, and in parallel proteomic and transcriptomic studies. The new field of toxicoproteomics is uniquely positioned toward an expanded understanding of protein expression during toxicity and environmental disease for the advancement of public health.
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Affiliation(s)
- Barbara A Wetmore
- National Center for Toxicogenomics, National Institute of Environmental Health Sciences, Research Triangle Park, North Caroline 27709, USA
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Tracing the voyage of SELDI-TOF MS in cancer biomarker discovery and its current depreciation trend – need for resurrection? Trends Analyt Chem 2016. [DOI: 10.1016/j.trac.2015.10.004] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Theophilou G, Paraskevaidi M, Lima KMG, Kyrgiou M, Martin-Hirsch PL, Martin FL. Extracting biomarkers of commitment to cancer development: potential role of vibrational spectroscopy in systems biology. Expert Rev Mol Diagn 2015; 15:693-713. [DOI: 10.1586/14737159.2015.1028372] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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Li X, Tan J, Yu J, Feng J, Pan A, Zheng S, Wu J. Use of a porous silicon–gold plasmonic nanostructure to enhance serum peptide signals in MALDI-TOF analysis. Anal Chim Acta 2014; 849:27-35. [DOI: 10.1016/j.aca.2014.08.028] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2014] [Revised: 08/14/2014] [Accepted: 08/14/2014] [Indexed: 11/24/2022]
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Di Domenico F, De Marco F, Perluigi M. Proteomics strategies to analyze HPV-transformed cells: relevance to cervical cancer. Expert Rev Proteomics 2014; 10:461-72. [DOI: 10.1586/14789450.2013.842469] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
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Abstract
In the past several years, proteomics and its subdiscipline clinical proteomics have been engaged in the discovery of the next generation protein of biomarkers. As the effort and the intensive debate it has sparked continue, it is becoming apparent that a paradigm shift is needed in proteomics in order to truly comprehend the complexity of the human proteome and assess its subtle variations among individuals. This review introduces the concept of population proteomics as a future direction in proteomics research. Population proteomics is the study of protein diversity in human populations. High-throughput, top-down mass spectrometric approaches are employed to investigate, define and understand protein diversity and modulations across and within populations. Population proteomics is a discovery-oriented endeavor with a goal of establishing the incidence of protein structural variations and quantitative regulation of these modifications. Assessing human protein variations among and within populations is viewed as a paramount undertaking that can facilitate clinical proteomics' effort in discovery and validation of protein features that can be used as markers for early diagnosis of disease, monitoring of disease progression and assessment of therapy. This review outlines the growing need for analyzing individuals' proteomes and describes the approaches that are likely to be applied in such a population proteomics endeavor.
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Affiliation(s)
- Dobrin Nedelkov
- Intrinsic Bioprobes, Inc., 625 S. Smith Rd, Suite 22, Tempe, AZ 85281, USA.
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12
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Glycoconjugate Vaccines Used for Prevention from Biological Agents: Tandem Mass Spectrometric Analysis. DETECTION OF CHEMICAL, BIOLOGICAL, RADIOLOGICAL AND NUCLEAR AGENTS FOR THE PREVENTION OF TERRORISM 2014. [DOI: 10.1007/978-94-017-9238-7_16] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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13
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Tears as a source of biomarkers for ocular and systemic diseases. Exp Eye Res 2013; 117:126-37. [DOI: 10.1016/j.exer.2013.07.015] [Citation(s) in RCA: 143] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2013] [Revised: 07/05/2013] [Accepted: 07/12/2013] [Indexed: 12/23/2022]
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Mo HH, Lee SE, Son J, Hwang JM, Bae YJ, Cho K. Exposure of mayfly Ephemera orientalis (Ephemeroptera) eggs to heavy metals and discovery of biomarkers. ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY 2013; 36:1167-1175. [PMID: 24184569 DOI: 10.1016/j.etap.2013.10.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/26/2013] [Revised: 09/28/2013] [Accepted: 10/07/2013] [Indexed: 06/02/2023]
Abstract
The objective of this study was to assess acute toxicity of heavy metals in eggs of mayfly Ephemera orientalis McLachlan, and to elucidate relationships between heavy metal toxicity and protein expression patterns determined using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). Acute toxicity analysis was conducted using five heavy metals (cadmium, chromium, copper, lead, and mercury), and the toxicity endpoint was established from the egg hatching rate during a 14-day exposure period. Median hatching toxicity (HC₅₀) values were determined for each heavy metal, and the most toxic heavy metal was found to be mercury (0.11 mg/L), followed by copper (0.32 mg/L) and lead (4.39 mg/L). E. orientalis eggs were highly tolerant to cadmium and chromium (>120 mg/L). Proteinchip array analysis using a strong anion exchange proteinchip (Q10) in conjunction with SELDI-TOF-MS was used to assess the protein expression patterns after exposure to heavy metals at the EHC10 (prohibiting hatching concentration to 10% eggs), except for cadmium and chromium, which were used at concentrations of 1, 10, and 100mg/L. Three novel biomarker candidate proteins, i.e., 4269, 4283, and 4623 m/z, were identified for the detection of heavy metal toxicity in aquatic ecosystems at the level of HC₁₀ in E. orientalis eggs. SELDI-TOF MS analysis for detecting differential expression of proteins was found to be more effective than Q10 proteinchip separation in the mayfly eggs.
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Affiliation(s)
- Hyoung-ho Mo
- Division of Environmental Science and Ecological Engineering, Korea University, Anam-Dong, Sungbuk-Gu, Seoul 136-701, South Korea
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Buhimschi AD, Gasparro FP. UVA and UVB-Induced 8-Methoxypsoralen Photoadducts and a Novel Method for their Detection by Surface-Enhanced Laser Desorption Ionization Time-of-Flight Mass Spectrometry (SELDI-TOF MS). Photochem Photobiol 2013; 90:241-6. [DOI: 10.1111/php.12171] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2013] [Accepted: 08/28/2013] [Indexed: 11/28/2022]
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Han MY, Dai JJ, Zhang Y, Lin Q, Jiang M, Xu XY, Liu Q. Identification of osteoarthritis biomarkers by proteomic analysis of synovial fluid. J Int Med Res 2013; 40:2243-50. [PMID: 23321181 DOI: 10.1177/030006051204000622] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
OBJECTIVE To use proteomic analysis to identify novel candidate biomarker proteins in synovial fluid for the differential diagnosis of osteoarthritis and rheumatoid arthritis. METHODS Synovial fluid samples were analysed using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). Data were used to generate an artificial neural network (ANN). The identification of one protein peak was confirmed via Western blotting. RESULTS Fluid samples were analysed from 36 patients with osteoarthritis and 24 with rheumatoid arthritis. In total, three protein peaks (mass-to-charge ratio [m/z] 3893, 10,576 and 14,175 Da) were identified as potential biomarkers for osteoarthritis. The ANN differentiated between osteoarthritis and rheumatoid arthritis with a sensitivity of 89.4% and a specificity of 91.2%. The protein peak at m/z 10 576 was identified as S100 calcium binding protein A12 (S100A12). CONCLUSIONS A combination of SELDI-TOF-MS and ANN identified osteoarthritis biomarkers. SELDI-TOF-MS may be a useful tool in the screening of synovial fluid for osteoarthritis diagnosis.
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Affiliation(s)
- M Y Han
- Cancer Therapy and Research Centre, Shandong Provincial Hospital, Shandong University, Jinan Province, China
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Clark DA, Rahmati M, Gohner C, Bensussan A, Markert UR, Chaouat G. Seminal plasma peptides may determine maternal immune response that alters success or failure of pregnancy in the abortion-prone CBAxDBA/2 model. J Reprod Immunol 2013; 99:46-53. [PMID: 23701834 DOI: 10.1016/j.jri.2013.03.006] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2012] [Revised: 03/27/2013] [Accepted: 03/28/2013] [Indexed: 11/28/2022]
Abstract
Spontaneous abortion (resorption) in the DBA/2-mated CBA/J mouse involves a deficiency in Treg cell activity against paternal antigens at the time of mating. Preimmunization of female CBA/J by BALB/c splenocytes, but not DBA/2 splenocytes, protects against subsequent abortions after a CBAxDBA/2 mating. Previous immunogenetic studies with BALB/cxDBA/2 recombinants have indicated that H-2(d)-restricted presentation of a single minor non-H-2(d) peptide might be responsible for protection, while the product of a second independent allele might promote abortions. Using brefeldin-treated BALB/c and DBA/2 splenocytes, we found that incubation in BALB/c seminal plasma rendered DBA/2 splenocytes protective and DBA/2 seminal plasma eliminated protection. The active protective moiety was <10 kD consistent with a peptide. DBA/2 seminal plasma contained a <10-kD peptide that boosted the abortion rate. Maternal H-2(k) CBA/J splenocytes were unable to present the protective activity. Amicon fractionation also unmasked a <10-kD activity in DBA/2 seminal plasma that could boost abortion rates when presented by BALB/c splenocytes. SELDI-TOF mass spectrometry proteomic analysis of <10-kD filtrates reproducibly detected 1416, 1468, 1774 D peptides in BALB/c that were reduced or absent in DBA/2, and the presence of 2662, 4559 and 5320 D molecules in DBA/2, the latter two definitely not present in BALB/c. Direct antigen presentation of paternal H-2(d)-restricted paternal peptides (600-1800 D) may prevent the rejection of the CBAxDBA/2 embryos, and larger sized peptides may bind to immunizing splenocytes and augment abortion mechanisms.
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Affiliation(s)
- David A Clark
- Department of Medicine, Molecular Medicine & Pathology, Ob-Gyn., McMaster University, Health Sciences Centre, Room 3H1E, Hamilton, Ontario, Canada L8S 4K1; Department of Immunology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
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Azzam S, Broadwater L, Li S, Freeman EJ, McDonough J, Gregory RB. A SELDI mass spectrometry study of experimental autoimmune encephalomyelitis: sample preparation, reproducibility, and differential protein expression patterns. Proteome Sci 2013; 11:19. [PMID: 23635033 PMCID: PMC3682907 DOI: 10.1186/1477-5956-11-19] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2012] [Accepted: 03/25/2013] [Indexed: 12/21/2022] Open
Abstract
Background Experimental autoimmune encephalomyelitis (EAE) is an autoimmune, inflammatory disease of the central nervous system that is widely used as a model of multiple sclerosis (MS). Mitochondrial dysfunction appears to play a role in the development of neuropathology in MS and may also play a role in disease pathology in EAE. Here, surface enhanced laser desorption ionization mass spectrometry (SELDI-MS) has been employed to obtain protein expression profiles from mitochondrially enriched fractions derived from EAE and control mouse brain. To gain insight into experimental variation, the reproducibility of sub-cellular fractionation, anion exchange fractionation as well as spot-to-spot and chip-to-chip variation using pooled samples from brain tissue was examined. Results Variability of SELDI mass spectral peak intensities indicates a coefficient of variation (CV) of 15.6% and 17.6% between spots on a given chip and between different chips, respectively. Thinly slicing tissue prior to homogenization with a rotor homogenizer showed better reproducibility (CV = 17.0%) than homogenization of blocks of brain tissue with a Teflon® pestle (CV = 27.0%). Fractionation of proteins with anion exchange beads prior to SELDI-MS analysis gave overall CV values from 16.1% to 18.6%. SELDI mass spectra of mitochondrial fractions obtained from brain tissue from EAE mice and controls displayed 39 differentially expressed proteins (p≤ 0.05) out of a total of 241 protein peaks observed in anion exchange fractions. Hierarchical clustering analysis showed that protein fractions from EAE animals with severe disability clearly segregated from controls. Several components of electron transport chain complexes (cytochrome c oxidase subunit 6b1, subunit 6C, and subunit 4; NADH dehydrogenase flavoprotein 3, alpha subcomplex subunit 2, Fe-S protein 4, and Fe-S protein 6; and ATP synthase subunit e) were identified as possible differentially expressed proteins. Myelin Basic Protein isoform 8 (MBP8) (14.2 kDa) levels were lower in EAE samples with advanced disease relative to controls, while an MBP fragment (12. 4kDa), likely due to calpain digestion, was increased in EAE relative to controls. The appearance of MBP in mitochondrially enriched fractions is due to tissue freezing and storage, as MBP was not found associated with mitochondria obtained from fresh tissue. Conclusions SELDI mass spectrometry can be employed to explore the proteome of a complex tissue (brain) and obtain protein profiles of differentially expressed proteins from protein fractions. Appropriate homogenization protocols and protein fractionation using anion exchange beads can be employed to reduce sample complexity without introducing significant additional variation into the SELDI mass spectra beyond that inherent in the SELDI- MS method itself. SELDI-MS coupled with principal component analysis and hierarchical cluster analysis provides protein patterns that can clearly distinguish the disease state from controls. However, identification of individual differentially expressed proteins requires a separate purification of the proteins of interest by polyacrylamide electrophoresis prior to trypsin digestion and peptide mass fingerprint analysis, and unambiguous identification of differentially expressed proteins can be difficult if protein bands consist of several proteins with similar molecular weights.
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Affiliation(s)
- Sausan Azzam
- Department of Chemistry and Biochemistry, Kent State University, Kent, Ohio 44242, USA.
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Zürbig P, Jahn H. Use of proteomic methods in the analysis of human body fluids in Alzheimer research. Electrophoresis 2013; 33:3617-30. [PMID: 23160951 DOI: 10.1002/elps.201200360] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2012] [Revised: 09/27/2012] [Accepted: 09/27/2012] [Indexed: 01/23/2023]
Abstract
Proteomics is the study of the entire population of proteins and peptides in an organism or a part of it, such as a cell, tissue, or fluids like cerebrospinal fluid, plasma, serum, urine, or saliva. It is widely assumed that changes in the composition of the proteome may reflect disease states and provide clues to its origin, eventually leading to targets for new treatments. The ability to perform large-scale proteomic studies now is based jointly on recent advances in our analytical methods. Separation techniques like CE and 2DE have developed and matured. Detection methods like MS have also improved greatly in the last 5 years. These developments have also driven the fields of bioinformatics, needed to deal with the increased data production and systems biology. All these developing methods offer specific advantages but also come with certain limitations. This review describes the different proteomic methods used in the field, their limitations, and their possible pitfalls. Based on a literature search in PubMed, we identified 112 studies that applied proteomic techniques to identify biomarkers for Alzheimer disease. This review describes the results of these studies on proteome changes in human body fluids of Alzheimer patients reviewing the most important studies. We extracted a list of 366 proteins and peptides that were identified by these studies as potential targets in Alzheimer research.
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20
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Sokolowska I, Wetie AGN, Woods AG, Darie CC. Applications of Mass Spectrometry in Proteomics. Aust J Chem 2013. [DOI: 10.1071/ch13137] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Characterisation of proteins and whole proteomes can provide a foundation to our understanding of physiological and pathological states and biological diseases or disorders. Constant development of more reliable and accurate mass spectrometry (MS) instruments and techniques has allowed for better identification and quantification of the thousands of proteins involved in basic physiological processes. Therefore, MS-based proteomics has been widely applied to the analysis of biological samples and has greatly contributed to our understanding of protein functions, interactions, and dynamics, advancing our knowledge of cellular processes as well as the physiology and pathology of the human body. This review will discuss current proteomic approaches for protein identification and characterisation, including post-translational modification (PTM) analysis and quantitative proteomics as well as investigation of protein–protein interactions (PPIs).
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Pinet F. Proteomic analysis of plasma of patients with left ventricular remodeling after myocardial infarction: usefulness of SELDI-TOF. Methods Mol Biol 2013; 1000:201-207. [PMID: 23585094 DOI: 10.1007/978-1-62703-405-0_15] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/02/2023]
Abstract
SELDI-TOF and depletion of major blood proteins is one of the most promising approaches for accessing low-abundance biomarkers. The use of combinatorial peptide ligand library (CPLL) for selecting the low-abundance proteins and of liquid-phase isoelectric focusing for purifying the corresponding proteins was tested in plasma or serum from patients with myocardial infarction (MI). Here, we describe the SELDI profiling of CPLL-treated plasma to select low-abundance proteins in plasma and the strategy for purification and mass spectrometry identification. This approach shows the potential to select and identify candidate biomarkers in patients with left ventricular remodeling after MI.
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Abstract
Surface-enhanced laser desorption/ionization mass spectrometry (SELDI-MS) is an established, chip-based method for protein profiling, typically used for biomarker discovery. By combining retention chromatography and mass spectrometry on the same analytical platform, it allows for reliable analyses of small sample quantities in a high-throughput fashion. As such, it is a highly useful tool for a wide range of research fields. We have successfully applied it on brain tumor tissue samples to screen for differences in protein expression between invasive and noninvasive benign meningioma. This chapter lays out the details of the protocols we used, and can serve as a guide for protein expression profiling experiments on brain tumor tissue using SELDI-MS.
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Affiliation(s)
- Carl Wibom
- Department of Oncology, Institution for Radiation Sciences, Umeå, Sweden
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Boccardi C, Rocchiccioli S, Cecchettini A, Mercatanti A, Citti L. An automated plasma protein fractionation design: high-throughput perspectives for proteomic analysis. BMC Res Notes 2012; 5:612. [PMID: 23116412 PMCID: PMC3517536 DOI: 10.1186/1756-0500-5-612] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2012] [Accepted: 10/26/2012] [Indexed: 01/17/2023] Open
Abstract
Background Human plasma, representing the most complete record of the individual phenotype, is an appealing sample for proteomics analysis in clinical applications. Up to today, the major obstacle in a proteomics study of plasma is the large dynamic range of protein concentration and the efforts of many researchers focused on the resolution of this important drawback. Findings In this study, proteins from pooled plasma samples were fractionated according to their chemical characteristics on a home-designed SPE automated platform. The resulting fractions were digested and further resolved by reversed-phase liquid chromatography coupled with MALDI TOF/TOF mass spectrometry. A total of 712 proteins were successfully identified until a concentration level of ng/mL. Pearson correlation coefficient was used to test reproducibility. Conclusions Our multidimensional fractionation approach reduced the analysis time (2 days are enough to process 16 plasma samples filling a 96-well plate) over the conventional gel-electrophoresis or multi-LC column based methods. The robotic processing, avoiding contaminants or lack of sample handling skill, promises highly reproducible specimen analyses (more than 85% Pearson correlation). The automated platform here presented is flexible and easily modulated changing fractioning elements or detectors.
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Affiliation(s)
- Claudia Boccardi
- Institute of Clinical Physiology-CNR, Via Moruzzi 1, 56124 Pisa, Italy
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Tao YL, Li Y, Gao J, Liu ZG, Tu ZW, Li G, Xu BQ, Niu DL, Jiang CB, Yi W, Li ZQ, Li J, Wang YM, Cheng ZB, Liu QD, Bai L, Zhang C, Zhang JY, Zeng MS, Xia YF. Identifying FGA peptides as nasopharyngeal carcinoma-associated biomarkers by magnetic beads. J Cell Biochem 2012; 113:2268-78. [PMID: 22334501 DOI: 10.1002/jcb.24097] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
Early diagnosis and treatment is known to improve prognosis for nasopharyngeal carcinoma (NPC). The study determined the specific peptide profiles by comparing the serum differences between NPC patients and healthy controls, and provided the basis for the diagnostic model and identification of specific biomarkers of NPC. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) can be used to detect the molecular mass of peptides. Mass spectra of peptides were generated after extracting and purification of 40 NPC samples in the training set, 21 in the single center validation set and 99 in the multicenter validation set using weak cationic-exchanger magnetic beads. The spectra were analyzed statistically using FlexAnalysis™ and ClinProt™ bioinformatics software. The four most significant peaks were selected out to train a genetic algorithm model to diagnose NPC. The diagnostic sensitivity and specificity were 100% and 100% in the training set, 90.5% and 88.9% in the single center validation set, 91.9% and 83.3% in the multicenter validation set, and the false positive rate (FPR) and false negative rate (FNR) were obviously lower in the NPC group (FPR, 16.7%; FNR, 8.1%) than in the other cancer group (FPR, 39%; FNR, 61%), respectively. So, the diagnostic model including four peptides can be suitable for NPC but not for other cancers. FGA peptide fragments identified may serve as tumor-associated biomarkers for NPC.
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Affiliation(s)
- Ya-Lan Tao
- Department of Radiation Oncology, Cancer Center, Sun Yat-Sen University, Guangzhou, Guangdong, People's Republic of China
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Demiralp DO, Peker S, Turgut B, Akar N. Comprehensive identification of erythrocyte membrane protein deficiency by 2D gel electrophoresis based proteomic analysis in hereditary elliptocytosis and spherocytosis. Proteomics Clin Appl 2012; 6:403-11. [DOI: 10.1002/prca.201200010] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Affiliation(s)
| | - Selen Peker
- Ankara University Biotechnology Institute; Ankara Turkey
| | - Burhan Turgut
- Department; of Child Health and Diseases; TOBB University; Ankara Turkey
| | - Nejat Akar
- Department of Hematology, Medical School; Namik Kemal University; Tekirdag Turkey
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Martiny D, Vandenberg O. Exploitation de la spectrométrie de masse en microbiologie : une révolution. ACTA ACUST UNITED AC 2012. [DOI: 10.1016/j.immbio.2012.04.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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Identification of a Novel Biomarker for Biliary Tract Cancer Using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry. INTERNATIONAL JOURNAL OF PROTEOMICS 2012; 2012:108609. [PMID: 22888427 PMCID: PMC3410312 DOI: 10.1155/2012/108609] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/10/2012] [Accepted: 06/09/2012] [Indexed: 01/27/2023]
Abstract
Early diagnosis of biliary tract cancer (BTC) is important for curative surgical resection. Current tumor markers of BTC are unsatisfactory in terms of sensitivity and specificity. In a search for novel biomarkers for BTC, serum samples obtained from 62 patients with BTC were compared with those from patients with benign biliary diseases and from healthy controls, using the MALDI-TOF/TOF ClinProt system. Initial screening and further validation identified a peak at 4204 Da with significantly greater intensity in the BTC samples. The 4204 Da peak was partially purified and identified as a fragment of prothrombin by amino acid sequencing. The sensitivity of the 4204 Da peptide for detection of stage I BTC cancer was greater than those for CEA and CA19-9. Also, serum levels of the 4204 Da peptide were above the cut-off level in 15 (79%) of 19 cases in which the CEA and CA19-9 levels were both within their cut-off values. Receiver operating characteristic analysis showed that the combination of the 4204 Da peptide and CA19-9 was significantly more sensitive for detection of stage I BTC cancer compared to CEA and CA19-9. These results suggest that this protein fragment may be a promising biomarker for biliary tract cancer.
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High throughput profiling of serum phosphoproteins/peptides using the SELDI-TOF-MS platform. Methods Mol Biol 2012; 818:199-216. [PMID: 22083825 DOI: 10.1007/978-1-61779-418-6_14] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/15/2022]
Abstract
Protein phosphorylation is a dynamic post-translational modification that plays a critical role in the regulation of a wide spectrum of biological events and cellular functions including signal transduction, gene expression, cell proliferation, and apoptosis. Determination of the sites and magnitudes of protein phosphorylation has been an essential step in the analysis of the control of many biological systems. A high throughput analysis of phosphorylation of proteins would provide a simple, logical, and useful tool for a functional dissection and prediction of biological functions and signaling pathways in association with these important molecular events. We have developed a functional proteomics technique using the ProteinChip array-based SELDI-TOF-MS analysis for high throughput profiling of phosphoproteins/phosphopeptides in human serum for the early detection and diagnosis as well as for the molecular staging of human cancer. The methodology and experimental approach consists of five steps: (1) generation of a total peptide pool of serum proteins by a global trypsin digestion; (2) rapid isolation of phosphopeptides from the total serum peptide pool by an affinity selection, purification, and enrichment using a novel automated micro-bioprocessing system with phospho-antibody-conjugated paramagnetic beads and a hybrid magnet plate; (3) high throughput phosphopeptide analysis on ProteinChip arrays by automated SELDI-TOF-MS; and (4) bioinformatics and statistical methods for data analysis. This method with appropriate modifications may be equally applicable to serine-, threonine- and tyrosine-phosphorylated proteins and for selectively isolating, profiling, and identifying phosphopeptides present in a highly complex phosphor-peptide mixture prepared from various human specimens such as cells, tissue samples, and serum and other body fluids.
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Rodthongkum N, Ramireddy R, Thayumanavan S, Vachet RW. Selective enrichment and sensitive detection of peptide and protein biomarkers in human serum using polymeric reverse micelles and MALDI-MS. Analyst 2012; 137:1024-30. [PMID: 22193368 PMCID: PMC3771100 DOI: 10.1039/c2an16089g] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Reverse-micelle forming amphiphilic homopolymers with carboxylic acid and quaternary amine substituents are used to selectively enrich biomarker peptides and protein fragments from human serum prior to matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS) analysis. After depletion of human serum albumin (HSA) and immunoglobulin G (IgG), low abundance peptide biomarkers can be selectively enriched and detected by MALDI-MS at clinically relevant concentrations by using the appropriate homopolymer(s) and extraction pH value(s). Three breast cancer peptide biomarkers, bradykinin, C4a, and ITIH(4), were chosen to test this new approach, and detection limits of 0.5 ng mL(-1), 0.08 ng mL(-1), and 0.2 ng mL(-1), respectively, were obtained. In addition, the amphiphilic homopolymers were used to detect prostate specific antigen (PSA) at concentrations as low as 0.5 ng mL(-1) by targeting a surrogate peptide fragment of this protein biomarker. Selective enrichment and sensitive MS detection of low abundance peptide/protein biomarkers by these polymeric reverse micelles should be a sensitive and straightforward approach for biomarker screening in human serum.
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Affiliation(s)
- Nadnudda Rodthongkum
- Department of Chemistry, University of Massachusetts, Amherst, Massachusetts 01003
| | - Rajasekhar Ramireddy
- Department of Chemistry, University of Massachusetts, Amherst, Massachusetts 01003
| | - S. Thayumanavan
- Department of Chemistry, University of Massachusetts, Amherst, Massachusetts 01003
| | - Richard W. Vachet
- Department of Chemistry, University of Massachusetts, Amherst, Massachusetts 01003
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Kurkina T, Balasubramanian K. Towards in vitro molecular diagnostics using nanostructures. Cell Mol Life Sci 2012; 69:373-88. [PMID: 22009454 PMCID: PMC11115035 DOI: 10.1007/s00018-011-0855-7] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2011] [Revised: 09/29/2011] [Accepted: 09/29/2011] [Indexed: 10/16/2022]
Abstract
Nanostructures appear to be promising for a number of applications in molecular diagnostics, mainly due to the increased surface-to-volume ratio they can offer, the very low limit of detection achievable, and the possibility to fabricate point-of-care diagnostic devices. In this paper, we review examples of the use of nanostructures as diagnostic tools that bring in marked improvements over prevalent classical assays. The focus is laid on the various sensing paradigms that possess the potential or have demonstrated the capability to replace or augment current analytical strategies. We start with a brief introduction of the various types of nanostructures and their physical properties that determine the transduction principle. This is followed by a concise collection of various functionalization protocols used to immobilize biomolecules on the nanostructure surface. The sensing paradigms are discussed in two contexts: the nanostructure acting as a label for detection, or the nanostructure acting as a support upon which the molecular recognition events take place. In order to be successful in the field of molecular diagnostics, it is important that the nanoanalytical tools be evaluated in the appropriate biological environment. The final section of the review compiles such examples, where the nanostructure-based diagnostic tools have been tested on realistic samples such as serum, demonstrating their analytical power even in the presence of complex matrix effects. The ability of nanodiagnostic tools to detect ultralow concentrations of one or more analytes coupled with portability and the use of low sample volumes is expected to have a broad impact in the field of molecular diagnostics.
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Affiliation(s)
- Tetiana Kurkina
- Max-Planck-Institute for Solid State Research, Heisenbergstrasse 1, 70569 Stuttgart, Germany
| | - Kannan Balasubramanian
- Max-Planck-Institute for Solid State Research, Heisenbergstrasse 1, 70569 Stuttgart, Germany
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31
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Elucidating the role of metals in Alzheimer's disease through the use of Surface-Enhanced Laser Desorption/Ionisation time-of-flight mass spectrometry. Methods Mol Biol 2011; 752:229-40. [PMID: 21713641 DOI: 10.1007/978-1-60327-223-0_15] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/15/2023]
Abstract
Alzheimer's disease (AD) is a highly heterogeneous and progressive dementia which is characterised by a progressive decline in cognitive functioning, selective neuronal atrophy, and loss of cortical volume in areas involved in learning and memory. However, recent research has indicated that the AD-affected brain is also besieged by increases in oxidative stress as well as perturbations to the homeostasis of biometals, such as copper and iron. These metals are known to interact with the neuropathological hallmark of AD, the β-amyloid peptide (Aβ), in a manner which increases Aβ's neurotoxic effects. This knowledge has led to the development of therapeutic measures which act to restore biometal homeostasis within the AD brain. This chapter outlines how Surface-Enhanced Laser Desorption/Ionisation Time-of-Flight Mass Spectrometry can be used to monitor Aβ levels within biological systems as well as describing the use of immobilised metal affinity capture in the observation of synthetic Aβ peptides.
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Uleberg KE, Munk AC, Skaland I, Furlan C, van Diermen B, Gudlaugsson E, Janssen EAM, Malpica A, Feng W, Hjelle A, Baak JPA. A protein profile study to discriminate CIN lesions from normal cervical epithelium. Cell Oncol (Dordr) 2011; 34:443-50. [PMID: 21573931 PMCID: PMC3219864 DOI: 10.1007/s13402-011-0047-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/01/2011] [Indexed: 12/01/2022] Open
Abstract
BACKGROUND Cervical intraepithelial neoplasia (CIN), a frequently encountered disease caused by Human Papilloma Virus (HPV) is often diagnosed in formaldehyde-fixed paraffin embedded (FFPE) punch biopsies. Since it is known that this procedure strongly affects the water-soluble proteins contained in the cervical tissue we decided to investigate whether a water-soluble protein-saving biopsy processing method can be used to support the diagnosis of normal and CIN. METHODS Cervical punch biopsies from 55 women were incubated for 24 h at 4°C in RPMI1640 medium for protein analysis prior to usual FFPE processing and p16 and Ki67-supported histologic consensus diagnosis was assessed. The biopsy supernatants were subjected to surface-enhanced laser desorption-ionization time of flight mass spectrometry (SELDI-TOF MS) for identifying differentially expressed proteins. Binary logistic regression and classification and regression trees (CART) were used to develop a classification model. RESULTS The age of the patients ranged from 26 to 40 years (median 29.7). The consensus diagnoses were normal cervical tissue (n = 10) and CIN2-3 (n = 45). The mean protein concentration was 1.00 and 1.09 mg/ml in the normal and CIN2-3 group, respectively. The peak detection and clustering process resulted in 40 protein peaks. Many of these peaks differed between the two groups, but only three had independent discriminating power. The overall classification results were 88%. CONCLUSIONS Water-soluble proteins sampled from punch biopsies are promising to assist the diagnosis of normal and CIN2-3.
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Affiliation(s)
- Kai-Erik Uleberg
- Pathology Department, Stavanger University Hospital, Armauer Hansen Road 20, PO Box 8100, 4068 Stavanger, Norway
- International Research Institute of Stavanger (IRIS), Stavanger, Norway
- The Gade Institute, University of Bergen, Bergen, Norway
| | - Ane Cecilie Munk
- Pathology Department, Stavanger University Hospital, Armauer Hansen Road 20, PO Box 8100, 4068 Stavanger, Norway
- Gynaecology Department, Stavanger University Hospital, Armauer Hansen Road 20, Stavanger, Norway
| | - Ivar Skaland
- Pathology Department, Stavanger University Hospital, Armauer Hansen Road 20, PO Box 8100, 4068 Stavanger, Norway
| | - Cristina Furlan
- Pathology Department, Stavanger University Hospital, Armauer Hansen Road 20, PO Box 8100, 4068 Stavanger, Norway
| | - Bianca van Diermen
- Pathology Department, Stavanger University Hospital, Armauer Hansen Road 20, PO Box 8100, 4068 Stavanger, Norway
| | - Einar Gudlaugsson
- Pathology Department, Stavanger University Hospital, Armauer Hansen Road 20, PO Box 8100, 4068 Stavanger, Norway
- The Gade Institute, University of Bergen, Bergen, Norway
| | - Emiel A. M. Janssen
- Pathology Department, Stavanger University Hospital, Armauer Hansen Road 20, PO Box 8100, 4068 Stavanger, Norway
| | - Anais Malpica
- Departments of Pathology and Gynaecologic Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX USA
| | - Weiwei Feng
- Department of Gynaecology, Fudan University Gynecology and Obstetrics Hospital, Shanghai, China
| | - Anne Hjelle
- International Research Institute of Stavanger (IRIS), Stavanger, Norway
| | - Jan P. A. Baak
- Pathology Department, Stavanger University Hospital, Armauer Hansen Road 20, PO Box 8100, 4068 Stavanger, Norway
- The Gade Institute, University of Bergen, Bergen, Norway
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Liu JY, Jin L, Zhao MY, Zhang X, Liu CB, Zhang YX, Li FJ, Zhou JM, Wang HJ, Li JC. New serum biomarkers for detection of tuberculosis using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Clin Chem Lab Med 2011; 49:1727-1733. [PMID: 21671803 DOI: 10.1515/cclm.2011.634] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND New technologies for the early detection of tuberculosis (TB) are urgently needed. Pathological changes within an organ might be reflected in proteomic patterns in serum. The aim of the present study was to screen for the potential protein biomarkers in serum for the diagnosis of TB using proteomic fingerprint technology. METHODS Proteomic fingerprint technology combining protein chips with surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) was used to profile the serum proteins from 50 patients with TB, 25 patients with lung disease other than TB, and 25 healthy volunteers. The protein fingerprint expression of all the serum samples and the resulting profiles between TB and control groups were analyzed with the Biomarker Wizard system. RESULTS A total of 30 discriminating m/z peaks were detected that were related to TB (p<0.01). The model of biomarkers constructed by the Biomarker Patterns Software based on the three biomarkers (2024, 8007, and 8598 Da) generated excellent separation between the TB and control groups. The sensitivity was 84.0% and the specificity was 86.0%. Blind test data indicated a sensitivity of 80.0% and a specificity of 84.2%. CONCLUSIONS The data suggested a potential application of SELDI-TOF MS as an effective technology to profile serum proteome, and with pattern analysis, a diagnostic model comprising three potential biomarkers was indicated to differentiate people with TB and healthy controls rapidly and precisely.
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Affiliation(s)
- Ji-Yan Liu
- Institute of Cell Biology, Zhejiang University, Hangzhou, PR China
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Gold nanomaterials as a new tool for bioanalytical applications of laser desorption ionization mass spectrometry. Anal Bioanal Chem 2011; 402:601-23. [DOI: 10.1007/s00216-011-5120-2] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2011] [Revised: 05/13/2011] [Accepted: 05/17/2011] [Indexed: 10/18/2022]
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Detection of renal allograft dysfunction with characteristic protein fingerprint by serum proteomic analysis. Int Urol Nephrol 2011; 43:1009-17. [PMID: 21516471 DOI: 10.1007/s11255-011-9962-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2010] [Accepted: 03/30/2011] [Indexed: 12/20/2022]
Abstract
This study aimed to diagnose renal allograft dysfunction with specific biomarkers by serum proteomic analysis. Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) and bioinformatics (support vector machine and leave-one cross validation) were used to analyze serum proteome. Enrolled patients included 38 biopsy-proved acute rejection (BPAR), 10 acute tubular necrosis (ATN), 24 subclinical rejection (SCR) and 29 stable control recipients verified by protocol biopsy. A characteristic protein profile can be detected in each renal allograft dysfunction group. BPAR patients were differentiated from stable patients with markers of 9710.1, 4971, 6675.5, 8563.8, 6709.2, 9319 and 4476.7 Da with high sensitivity and specificity. ATN can be clearly distinguished from BPAR and stable control. Subclinical rejection differentiated from stable control with markers of 9193.1, 2759.1, 8464.6 Da. The independent blind test yielded with high specificity and sensitivity for each group. Serum proteome analysis by SELDI-TOF MS combined with bioinformatics in renal allograft dysfunction is valuable and promising. Specific markers were detected in each group. Identification of these proteins may prove useful as diagnostic markers for allograft dysfunction and better to elucidate the mechanism of acute rejection.
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36
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Application of serum protein fingerprint in diagnosis of coronary artery disease. Clin Biochem 2011; 44:185-91. [DOI: 10.1016/j.clinbiochem.2010.10.003] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2010] [Revised: 10/04/2010] [Accepted: 10/06/2010] [Indexed: 11/24/2022]
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Ge F, Bi LJ, Tao SC, Xu XD, Zhang ZP, Kitazato K, Zhang XE. Proteomic analysis of multiple myeloma: Current status and future perspectives. Proteomics Clin Appl 2011; 5:30-7. [DOI: 10.1002/prca.201000044] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
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Yano T, Sogawa K, Umemura H, Sakao S, Kasahara Y, Tanabe N, Kodera Y, Takiguchi Y, Tatsumi K, Nomura F. Serum Level of Fibrinogen A.ALPHA. Chain Fragment Increases in Chronic Thromboembolic Pulmonary Hypertension. Circ J 2011; 75:2675-82. [DOI: 10.1253/circj.cj-11-0045] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Affiliation(s)
- Toshiaki Yano
- Department of Respirology, Graduate School of Medicine, Chiba University
| | | | - Hiroshi Umemura
- Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University
| | - Seiichiro Sakao
- Department of Respirology, Graduate School of Medicine, Chiba University
| | - Yasunori Kasahara
- Department of Respirology, Graduate School of Medicine, Chiba University
| | - Nobuhiro Tanabe
- Department of Respirology, Graduate School of Medicine, Chiba University
| | - Yoshio Kodera
- Clinical Proteomics Center, Chiba University Hospital
- Department of Physics, School of Science, Kitasato University
| | - Yuichi Takiguchi
- Department of Respirology, Graduate School of Medicine, Chiba University
| | - Koichiro Tatsumi
- Department of Respirology, Graduate School of Medicine, Chiba University
| | - Fumio Nomura
- Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University
- Clinical Proteomics Center, Chiba University Hospital
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Strategy for purification and mass spectrometry identification of SELDI peaks corresponding to low-abundance plasma and serum proteins. J Proteomics 2010; 74:420-30. [PMID: 21184852 DOI: 10.1016/j.jprot.2010.12.005] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2010] [Revised: 12/13/2010] [Accepted: 12/15/2010] [Indexed: 12/22/2022]
Abstract
Analysis by SELDI-TOF-MS of low abundance proteins makes it possible to select peaks as candidate biomarkers. Our aim was to define a purification strategy to optimise identification by MS of peaks detected by SELDI-TOF-MS from plasma or serum, regardless of any treatment by a combinatorial peptide ligand library (CPLL). We describe 2 principal steps in purification. First, choosing the appropriate sample containing the selected peak requires setting up a databank that records all the m/z peaks detected from samples in different conditions. Second, the specific purification process must be chosen: separation was achieved with either chromatographic columns or liquid-phase isoelectric focusing, both combined when appropriate with reverse-phase chromatography. After purification, peaks were separated by gel electrophoresis and the candidate proteins were analyzed by nano-liquid-chromatography-MS/MS. We chose 4m/z peaks (9400, 13,571, 13,800 and 15,557) selected for their differential expression between two conditions, as examples to explain the different strategies of purification, and we successfully identified 3 of them. Despite some limitations, our strategy to purify and identify peaks selected from SELDI-TOF-MS analysis was effective.
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40
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Lee KK, Todorova K, Mandinova A. Maximizing early detection of esophageal squamous cell carcinoma via SILAC-proteomics. Cancer Biol Ther 2010; 10:811-3. [PMID: 20953140 PMCID: PMC3093917 DOI: 10.4161/cbt.10.8.13754] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2010] [Accepted: 09/26/2010] [Indexed: 11/19/2022] Open
Affiliation(s)
- Kevin K Lee
- Cutaneous Biology Research Center; Massachusetts General Hospital and Harvard Medical School; Charlestown; MA USA
- Broad Institute of Harvard and MIT; Cambridge Center; MA USA
| | - Kristina Todorova
- Cutaneous Biology Research Center; Massachusetts General Hospital and Harvard Medical School; Charlestown; MA USA
| | - Anna Mandinova
- Cutaneous Biology Research Center; Massachusetts General Hospital and Harvard Medical School; Charlestown; MA USA
- Broad Institute of Harvard and MIT; Cambridge Center; MA USA
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41
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Medvedovici A, Albu F, David V. HANDLING DRAWBACKS OF MASS SPECTROMETRIC DETECTION COUPLED TO LIQUID CHROMATOGRAPHY IN BIOANALYSIS. J LIQ CHROMATOGR R T 2010. [DOI: 10.1080/10826076.2010.484375] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Andrei Medvedovici
- a Department of Analytical Chemistry, Faculty of Chemistry , University of Bucharest , Bucharest , Romania
| | - Florin Albu
- b Bioanalytical Laboratory , S.C. LaborMed Pharma S.A. , Bucharest , Romania
| | - Victor David
- a Department of Analytical Chemistry, Faculty of Chemistry , University of Bucharest , Bucharest , Romania
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42
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Kawashima Y, Fukutomi T, Tomonaga T, Takahashi H, Nomura F, Maeda T, Kodera Y. High-yield peptide-extraction method for the discovery of subnanomolar biomarkers from small serum samples. J Proteome Res 2010; 9:1694-705. [PMID: 20184378 DOI: 10.1021/pr9008018] [Citation(s) in RCA: 73] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Serum proteins/peptides reflect physiological or pathological states in humans and are an attractive target for the discovery of disease biomarkers. However, the existence of high-abundance proteins and the large dynamic range of serum proteins/peptides make any quantitative analysis of low-abundance proteins/peptides challenging. Furthermore, analyses of peptides, including the cleaved fragments of proteins, are difficult because of carrier protein binding. Here, we developed a differential solubilization (DS) method to extract low-molecular-weight proteins/peptides in serum with good reproducibility and yield as compared to typical peptide-extraction methods such as organic solvent precipitation and ultrafiltration. Using the DS method combined with reverse-phase HPLC fractionation followed by MALDI-TOF-MS, we performed high-quality comparative analyses of more than 1500 peptides from 1 microL of serum samples, including low-abundance peptides in the subnanomolar range and containing many peptides bound to carrier proteins such as albumin. We applied this method and successfully discovered four new biomarker candidates of colon cancer, none of which have previously been observed in serum and one of which is a fragment of the protein zyxin that possibly originated from tumor cells. Our results indicate that serum peptide analyses based on the DS method should greatly contribute to the discovery of novel low-abundance biomarkers.
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Affiliation(s)
- Yusuke Kawashima
- Laboratory of Biomolecular Dynamics, Department of Physics, Kitasato University School of Science, Sagamihara, Kanagawa, Japan
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43
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Jimenez CR, Piersma S, Pham TV. High-throughput and targeted in-depth mass spectrometry-based approaches for biofluid profiling and biomarker discovery. Biomark Med 2010; 1:541-65. [PMID: 20477373 DOI: 10.2217/17520363.1.4.541] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Proteomics aims to create a link between genomic information, biological function and disease through global studies of protein expression, modification and protein-protein interactions. Recent advances in key proteomics tools, such as mass spectrometry (MS) and (bio)informatics, provide tremendous opportunities for biomarker-related clinical applications. In this review, we focus on two complementary MS-based approaches with high potential for the discovery of biomarker patterns and low-abundant candidate biomarkers in biofluids: high-throughput matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy-based methods for peptidome profiling and label-free liquid chromatography-based methods coupled to MS for in-depth profiling of biofluids with a focus on subproteomes, including the low-molecular-weight proteome, carrier-bound proteome and N-linked glycoproteome. The two approaches differ in their aims, throughput and sensitivity. We discuss recent progress and challenges in the analysis of plasma/serum and proximal fluids using these strategies and highlight the potential of liquid chromatography-MS-based proteomics of cancer cell and tumor secretomes for the discovery of candidate blood-based biomarkers. Strategies for candidate validation are also described.
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Affiliation(s)
- Connie R Jimenez
- OncoProteomics Laboratory, Department of Medical Oncology, VUmc Cancer Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
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44
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BRATSEVA YEV, MOSHKOVSKY SA, ZNAMENSKAYA LF, KUBANOVA AA, KUBANOV AA. Search for potential biomarkers of inveterate dermatoses by means of proteomic analysis. VESTNIK DERMATOLOGII I VENEROLOGII 2010. [DOI: 10.25208/vdv887] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022] Open
Abstract
The review covers the key achievements of proteome studies using mass spectrometry and two-dimensional electrophoresis methods in the field of dermatology Works studying the most prevalent chronic dermatoses such as psoriasis, atopic dermatitis, acne vulgaris and mycosis fungoidea are examined. Proteome analysis in dermatology is a promising technique today because it makes it possible to study molecular pathogenic mechanisms of skin chronic diseases in a greater detail. In addition, proteome technologies are aimed at searching for potential disease biomarkers and targets for drugs.
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45
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Yang H, Mao Y, Yu J, Chen J, He Q, Shou Z, Wu J, Chen Y, Zheng S. Diagnosis of C4d+ Renal Allograft Acute Humoral Rejection by Urine Protein Fingerprint Analysis. J Int Med Res 2010; 38:176-86. [PMID: 20233527 DOI: 10.1177/147323001003800120] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
This study aimed to develop urine protein fingerprint models for the diagnosis of acute rejection (AR) and complement split product positive (C4d+) acute humoral rejection (AHR) following renal allograft transplantation. Urine samples from 101 renal transplant recipients were analysed by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry combined with bioinformatics. The patients comprised 36 with stable allograft function (stable group), 10 with acute tubular necrosis (ATN) and 55 with AR (20 with C4d- acute cellular rejection [ACR] and 15 with C4d+ AHR). The ATN group was differentiated from the stable group with a sensitivity and specificity of 100% (pattern 1). The stable group was differentiated from the AR group with a specificity of 86.4% and a sensitivity of 85.4% (pattern 2). The C4d- ACR subgroup was differentiated from the C4d+ AHR subgroup with a specificity and sensitivity of 95% and 80%, respectively (pattern 3). It is concluded that urine protein fingerprint analysis can provide a noninvasive tool to diagnose AR and C4d+ AHR.
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Affiliation(s)
- H Yang
- The Kidney Disease Centre, Ministry of Public Health, The First Affiliated Hospital, Medical College, Zhejiang University, Hangzhou, China
| | - Y Mao
- The Kidney Disease Centre, Ministry of Public Health, The First Affiliated Hospital, Medical College, Zhejiang University, Hangzhou, China
| | - J Yu
- Cancer Institute, Ministry of Public Health, The First Affiliated Hospital, Medical College, Zhejiang University, Hangzhou, China
| | - J Chen
- The Kidney Disease Centre, Ministry of Public Health, The First Affiliated Hospital, Medical College, Zhejiang University, Hangzhou, China
- Key Laboratory of Combined Multiorgan Transplantation, Ministry of Public Health, The First Affiliated Hospital, Medical College, Zhejiang University, Hangzhou, China
| | - Q He
- The Kidney Disease Centre, Ministry of Public Health, The First Affiliated Hospital, Medical College, Zhejiang University, Hangzhou, China
| | - Z Shou
- The Kidney Disease Centre, Ministry of Public Health, The First Affiliated Hospital, Medical College, Zhejiang University, Hangzhou, China
| | - J Wu
- The Kidney Disease Centre, Ministry of Public Health, The First Affiliated Hospital, Medical College, Zhejiang University, Hangzhou, China
| | - Y Chen
- The Kidney Disease Centre, Ministry of Public Health, The First Affiliated Hospital, Medical College, Zhejiang University, Hangzhou, China
| | - S Zheng
- Cancer Institute, Ministry of Public Health, The First Affiliated Hospital, Medical College, Zhejiang University, Hangzhou, China
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46
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Zhang S, Liu J, Chen Y, Xiong S, Wang G, Chen J, Yang G. A novel strategy for MALDI-TOF MS analysis of small molecules. JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY 2010; 21:154-160. [PMID: 19906541 DOI: 10.1016/j.jasms.2009.09.024] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/27/2009] [Revised: 09/22/2009] [Accepted: 09/26/2009] [Indexed: 05/28/2023]
Abstract
Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) does not work efficiently on small molecules (usually with molecular weight below 500 Da) because of the interference of matrix-related peaks in low m/z region. The previous methods developed for this problem focused on reducing the peaks caused by the traditional matrices. Here, we report a novel strategy to analyze small molecules in a high and interference-free mass range by using metal-phthalocyanines (MPcs) as matrices which should be capable of forming matrix-analyte adducts. The mass of the target analyte was calculated by subtracting the mass of MPc from the mass of the MPc-analyte adduct. MPcs were also detectable and could serve as internal standards. Various MPcs with aromatic or aliphatic groups and different metal centers were then synthesized and explored. Aluminum-phthalocyanines (AlPcs), gallium-phthalocyanines (GaPcs), and indium-phthalocyanines (InPcs) were efficient matrices to form MPc-analyte adducts in either the positive or negative ion mode. The detection limits varied from 17 to 75 fmol, depending on analyte types. The mechanism of adducts formation was also proposed. Collectively, our strategy provides a novel and efficient way to analyze small molecules by MALDI-TOF MS.
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Affiliation(s)
- Shu Zhang
- Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China
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47
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Hu L, Ye M, Zou H. Recent advances in mass spectrometry-based peptidome analysis. Expert Rev Proteomics 2009; 6:433-47. [PMID: 19681678 DOI: 10.1586/epr.09.55] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
The peptidome, which is the low-molecular-weight subset of the proteome, has attracted increasing attention in recent years. However, with the interference of high-abundance protein components in complex biological mixtures (e.g., serum), selective extraction of endogenous peptides is the first and most important step before analyzing the peptidome. A number of methods and technologies have now been developed for the selective enrichment, fractionation, quantitative analysis of the endogenous peptides and their application in the potential biomarker discovery. This review will cover the methods and technologies developed in recent years for the peptidome analysis on the selective extraction, multidimensional separation and quantitative analysis, as well as their application for clinical diagnosis and biomarker discovery. The future prospects of the peptidome are also discussed.
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Affiliation(s)
- Lianghai Hu
- CAS Key Laboratory of Separation Science for Analytical Chemistry, National Chromatographic R&A Center, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, China
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48
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Mas VR, Fisher RA, Archer KJ, Maluf DG. Proteomics and liver fibrosis: identifying markers of fibrogenesis. Expert Rev Proteomics 2009; 6:421-31. [PMID: 19681677 DOI: 10.1586/epr.09.59] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Chronic hepatic disease damages the liver and the resulting wound-healing process might lead to liver fibrosis and subsequent cirrhosis development. Fibrosis is the excessive deposition of extracellular matrix (ECM) in the tissue as consequence of chronic liver damage. The fibrotic response triggers almost all of the complications of end-stage liver disease, including portal hypertension, ascites, encephalopathy, synthetic dysfunction and impaired metabolic capacity. Thus, efforts to understand and attenuate fibrosis have direct clinical implications. Reliable, accurate, disease-specific, noninvasive biomarkers of fibrosis and fibrogenesis in order to prevent or minimize the impact of the chronic liver disease progression are a critical need. This review aims to provide an overview of the possibilities that proteome technology can offer to the knowledge, diagnosis and prognosis of liver fibrosis.
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Affiliation(s)
- Valeria R Mas
- Transplant Molecular Laboratory, Transplant Division, Department of Surgery, Molecular Medicine Research Building, Virginia Commonwealth University, 1220 E. Broad Street, Richmond, VA 23298, USA.
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Wunschel D, Webb-Robertson BJ, Frevert CW, Skerrett S, Beagley N, Willse A, Colburn H, Antolick K. Differentiation of gram-negative bacterial aerosol exposure using detected markers in bronchial-alveolar lavage fluid. PLoS One 2009; 4:e7047. [PMID: 19756149 PMCID: PMC2737641 DOI: 10.1371/journal.pone.0007047] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2009] [Accepted: 08/11/2009] [Indexed: 12/28/2022] Open
Abstract
The identification of biosignatures of aerosol exposure to pathogens has the potential to provide useful diagnostic information. In particular, markers of exposure to different types of respiratory pathogens may yield diverse sets of markers that can be used to differentiate exposure. We examine a mouse model of aerosol exposure to known Gram negative bacterial pathogens, Francisella tularensis novicida and Pseudomonas aeruginosa. Mice were subjected to either a pathogen or control exposure and bronchial alveolar lavage fluid (BALF) was collected at four and twenty four hours post exposure. Small protein and peptide markers within the BALF were detected by matrix assisted laser desorption/ionization (MALDI) mass spectrometry (MS) and analyzed using both exploratory and predictive data analysis methods; principle component analysis and degree of association. The markers detected were successfully used to accurately identify the four hour exposed samples from the control samples. This report demonstrates the potential for small protein and peptide marker profiles to identify aerosol exposure in a short post-exposure time frame.
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Affiliation(s)
- David Wunschel
- Chemical and Biological Signature Sciences, Pacific Northwest National Laboratory, Richland, Washington, United States of America.
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50
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Sigdel TK, Klassen RB, Sarwal MM. Interpreting the proteome and peptidome in transplantation. Adv Clin Chem 2009; 47:139-69. [PMID: 19634780 DOI: 10.1016/s0065-2423(09)47006-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Publication of the human proteome has prompted efforts to develop high-throughput techniques that can catalogue and quantify proteins and peptides present in different tissue types. The field of proteomics aims to identify, quantify, analyze, and functionally define a large number of proteins in cellular processes in different disease states on a global scale. Peptidomics, a newer name in the -omics world, measures and identifies naturally occurring low molecular weight peptides, also providing an insight into enzymatic processes and molecular events occurring in the system of interest. One area of major interest is the use of proteomics to identify diagnostic and prognostic biomarkers for different diseases as well as for various clinical phenotypes in organ transplantation that can advance targeted therapy for various forms of graft injury. Outcomes in organ transplantation can be potentially improved by identifying noninvasive biomarkers that will serve as triggers that predate graft injury, and can offer a means to customize patient treatment by differentiating among causes of acute and chronic graft injury. Proteomic and peptidomic strategies can be harnessed for frequent noninvasive measurements in tissue fluids, allowing for serial monitoring of organ disease. In this review, we describe the basic techniques used in proteomic and peptidomic approaches, point out special considerations in using these methods, and discuss their applications in recently published studies in organ transplantation.
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Affiliation(s)
- Tara K Sigdel
- Department of Pediatrics-Nephrology, Stanford University Medical School, Stanford University, Stanford, California 94305, USA
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