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Article

Using Serum Amino Acids to Predict Traumatic Brain Injury: A Systematic Approach to Utilize Multiple Biomarkers

1
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30322, USA
2
Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
3
Center for Injury Research and Prevention, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA
4
Sports Medicine and Performance Center, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(5), 1786; https://doi.org/10.3390/ijms21051786
Received: 13 January 2020 / Revised: 17 February 2020 / Accepted: 2 March 2020 / Published: 5 March 2020
Traumatic brain injury (TBI) can cause biochemical and metabolomic alterations in the brain tissue and serum. These alterations can be used for diagnosis and prognosis of TBI. Here, the serum concentrations of seventeen amino acids (AA) were studied for their potential utility as biomarkers of TBI. Twenty-five female, 4-week-old piglets received diffuse (n = 13) or focal (n = 12) TBI. Blood samples were obtained both pre-injury and at either 24-h or 4-days post-TBI. To find a robust panel of biomarkers, the results of focal and diffuse TBIs were combined and multivariate logistic regression analysis, coupled with the best subset selection technique and repeated k-fold cross-validation method, was used to perform a thorough search of all possible subsets of AAs. The combination of serum glycine, taurine, and ornithine was optimal for TBI diagnosis, with 80% sensitivity and 86% overall prediction rate, and showed excellent TBI diagnostic performance, with 100% sensitivity and 78% overall prediction rate, on a separate validation dataset including four uninjured and five injured animals. We found that combinations of biomarkers outperformed any single biomarker. We propose this 3-AA serum biomarker panel to diagnose mild-to-moderate focal/diffuse TBI. The systematic approaches implemented herein can be used for combining parameters from various TBI assessments to develop/evaluate optimal multi-factorial diagnostic/prognostic TBI metrics. View Full-Text
Keywords: head injury; diagnostics; trauma; data science; biomarker; multivariate metrics head injury; diagnostics; trauma; data science; biomarker; multivariate metrics
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MDPI and ACS Style

Hajiaghamemar, M.; Kilbaugh, T.; Arbogast, K.B.; Master, C.L.; Margulies, S.S. Using Serum Amino Acids to Predict Traumatic Brain Injury: A Systematic Approach to Utilize Multiple Biomarkers. Int. J. Mol. Sci. 2020, 21, 1786. https://doi.org/10.3390/ijms21051786

AMA Style

Hajiaghamemar M, Kilbaugh T, Arbogast KB, Master CL, Margulies SS. Using Serum Amino Acids to Predict Traumatic Brain Injury: A Systematic Approach to Utilize Multiple Biomarkers. International Journal of Molecular Sciences. 2020; 21(5):1786. https://doi.org/10.3390/ijms21051786

Chicago/Turabian Style

Hajiaghamemar, Marzieh, Todd Kilbaugh, Kristy B. Arbogast, Christina L. Master, and Susan S. Margulies. 2020. "Using Serum Amino Acids to Predict Traumatic Brain Injury: A Systematic Approach to Utilize Multiple Biomarkers" International Journal of Molecular Sciences 21, no. 5: 1786. https://doi.org/10.3390/ijms21051786

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