Clinical proteomic biomarkers: relevant issues on study design &amp; technical considerations in biomarker development

Frantzi, Maria; Bhat, Akshay; Latosinska, Agnieszka

doi:10.1186/2001-1326-3-7

Cited by 111 publications

(85 citation statements)

References 204 publications

(277 reference statements)

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“…The validity of applying the proteomic profiling would require comprehensive verification via clinical trials on mice or by using advanced and sensitive molecular assays such as western plot (WP) or RT-PCR. To overcome some of the aforementioned problems, particularly in the biomarker discovery phase, genetically stable models of mice with the disease would simplify the initial use of protein biomarker for candidate selection [31].…”

Section: Methodsmentioning

confidence: 99%

Proteomic profile of acute myeloid leukaemia: A review update

Almaiman¹,

Abdullah²,

Abdul³

et al. 2016

Trop. J. Pharm Res

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Section: Methodsmentioning

confidence: 99%

Proteomic profile of acute myeloid leukaemia: A review update

Almaiman¹,

Abdullah²,

Abdul³

et al. 2016

Trop. J. Pharm Res

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“…Each dye and its protein sample, (control, case and internal standard) are pooled and separated simultaneously. This approach decreases the number of gels, as well as gel to gel variability, which is one of the drawbacks of the classical approach [15]. But since 2-DE is the oldest proteomic technique, all its advantages and disadvantages are well-known therefore making it possible to prioritize the problems and make them count as little as possible.…”

Section: Two-dimensional Gel Electrophoresismentioning

confidence: 99%

“…This method is also known as shotgun proteomics or bottom-up proteomics, and uses mean analysis of native or proteasederived peptides followed by sequencing with tandem mass spectrometry (MS/MS). The biological sample is often fractioned prior to analysis, due to the complexity of the sample, using different strategies such as chromatography, isoelectric focusing or a combination of both [15]. Proteomics is an expanding field and has become the technology of choice when studying proteins in living organisms and since proteomics developed it has become easier to identify potential new biomarkers.…”

Section: Biomarkers and Proteomicsmentioning

confidence: 99%

“…In general, proteomics uses two approaches in the discovery phase of biomarkers; gel-based proteomics and gel-free proteomics. Two-dimensional polyacrylamide gel electrophoresis (2-DE PAGE) is used, in combination with mass spectrometry, in gel-based proteomics and constitutes the first step to find potential candidate biomarkers (see Figure 2) [15]. The first dimension separates the proteins in a biological sample by isoelectric focusing (IEF), in other words, the proteins are positioned in a pH gradient according to their isoelectric point (pI).…”

Section: Biomarkers and Proteomicsmentioning

confidence: 99%

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Upper Airway Mucosal Inflammation : Proteomic Studies after Exposure to Irritants and Microbial Agents

Fornander¹

2015

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People are, in their daily lives, exposed to a number of airborne foreign compounds that do not normally affect the body. However, depending on the nature of these compounds, dose and duration of exposure, various airway symptoms may arise. Early symptoms are often manifested as upper airway mucosal inflammation which generates changes in protein composition in the airway lining fluid.This thesis aims at identifying, understanding mechanisms and characterizing protein alterations in the upper airway mucosa that can be used as potential new biomarkers for inflammation in the mucosa. The protein composition in the mucosa was studied by sampling of nasal lavage fluid that was further analyzed with a proteomic approach using two-dimensional gel electrophoresis and mass spectrometry. Additionally, by studying factors on site through environmental examination, health questionnaires and biological analyses, we have tried to understand the background to these protein alterations and their impact on health.Respiratory symptoms from the upper airways are common among people who are exposed to irritative and microbial agents. This thesis have focused on personnel in swimming pool facilities exposed to trichloramine, metal industry workers exposed to metalworking fluids, employees working in damp and moldy buildings and infants diagnosed with respiratory syncytial virus infection. The common denominator in these four studies is that the subjects experience upper airway mucosal inflammation, which is manifested as cough, rhinitis, phlegm etc. In the three occupational studies, the symptoms were work related. Notably, a high prevalence of perceived mucosal symptoms was shown despite the relatively low levels of airborne irritants revealed by the environmental examination. Protein profiling verified an ongoing inflammatory response by identification of several proteins that displayed altered levels. Interestingly, innate immune proteins dominated and four protein alterations occurred in most of the studies; SPLUNC1, protein S100A8 and S100A9 and alpha-1-antitrypsin. Similarly, these proteins were also found in nasal fluid from children with virus infection and in addition a truncated form of SPLUNC1 and two other S100 proteins (S100A7-like 2 and S100A16), not previously found in nasal secretion, were identified.Altogether, the results indicate the potential use of a proteomic approach for identifying new biomarkers for the upper respiratory tract at an early stage in the disease process after exposure to irritant and microbial agents. The results indicate an effect on the innate immunity system and the proteins; SPLUNC1, protein S100A8 and S100A9 and alpha-1-antitrypsin are especially promising new biomarkers. Moreover, further studies of these proteins may help us to understand the molecular mechanisms involved in irritant-induced airway inflammation. POPULÄRVETENSKAPLIG SAMMANFATTNING FÖRÄNDRAD PROTEINSAMMANSÄTTNING I DE ÖVRE LUFTVÄGARNA EFTER EXPONERING FÖR SLEMHINNEIRRITERANDE ÄMNENVarje dag utsätts vi för partikla...

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“…Well-designed proteomic studies that will adopt the guidelines of clinical proteomics are necessary to retest the biomarkers mentioned above and possibly discover additional candidates for the early detection of women at risk for pregnancy complications [18]. Use of standardized protocols in both, the preanalytical and the analytical steps, is essential in order to optimize results and allow for comparisons and meta-analyses.…”

mentioning

confidence: 99%