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Two-dimensional protein electrophoresis and multiple hypothesis testing to detect potential serum protein biomarkers
M K Robinson1, J E Myrick, L O Henderson
1Division of Environmental Health Laboratory Sciences, Centers for Disease Control and Prevention, Atlanta, GA 30341-3724, USA.
Insights
Researchers identified potential protein biomarkers for Fetal Alcohol Syndrome (FAS) by analyzing serum proteins. This could lead to a biochemical test for diagnosing FAS, improving surveillance and intervention efforts.
Area of Science:
- Biochemistry
- Proteomics
- Pediatrics
Background:
- Fetal Alcohol Syndrome (FAS) diagnosis lacks a specific biochemical test.
- Effective surveillance and intervention for FAS are hindered by diagnostic limitations.
Purpose of the Study:
- To identify potential protein biomarkers for Fetal Alcohol Syndrome (FAS).
- To investigate altered protein metabolism in children with FAS.
Main Methods:
- Serum proteins were analyzed using two-dimensional gel electrophoresis and image analysis.
- Comparative analysis of protein profiles between children with FAS and matched controls.
- Statistical analysis, including t-tests and discriminant analysis, was performed on over 1700 protein spots per gel.
Main Results:
- 21 potential protein biomarkers for FAS were identified with significant t-test differences (p < 0.02).
- 8 candidate biomarkers showed significant concentration differences (p < 0.01) between FAS cases and controls.
- Four groups of protein spots distinguished FAS cases from controls with no misclassifications using discriminant analysis.
Conclusions:
- Specific protein alterations in serum may serve as biomarkers for Fetal Alcohol Syndrome (FAS).
- These findings could facilitate the development of a biochemical diagnostic test for FAS.
- Further research is needed to validate these candidate biomarkers and understand their role in FAS.
Abstract:
Fetal alcohol syndrome (FAS) surveillance and intervention efforts are hampered by the lack of a specific biochemical test for diagnosis of the syndrome. Based on the hypothesis that abnormalities in growth and development (key features of FAS) involve altered protein metabolism, we analyzed serum proteins by two-dimensional gel electrophoresis and image analysis to search for potential protein biomarkers of FAS. Serum samples from 12 participants in whom FAS had been diagnosed and 8 sex- and age-matched participants whose mothers did not consume alcohol were analyzed in duplicate to determine whether the integrated intensities of matched proteins are significantly altered in children with FAS. Multiple hypothesis testing on 34 of the gels consisting of more than 1700 spots per gel revealed 21 proteins that we classified as potential protein biomarkers of FAS on the basis of significant t-test differences at p < 0.02. We classified 8 of the proteins as candidate biomarkers on the basis of significant concentration differences between case and control subjects at p < 0.01. One of the proteins is clearly an isoform of retinol binding protein; two appear in the area of the gel where alcohol dehydrogenase is expected to appear; one appears to be an isoform of alpha-1-antitrypsin; three appear to be isoforms of the beta-chain of haptoglobin; three may be forms of immunoglobulin light chains; and several others have not been associated with known proteins. No single protein differentiated all case subjects from control subjects, but stepwise canonical discriminant analyses revealed four groups of spots that distinguished between FAS case and control subjects with no misclassifications.(ABSTRACT TRUNCATED AT 250 WORDS)