TY - JOUR
T1 - Harmonization of pipeline for preclinical multicenter plasma protein and miRNA biomarker discovery in a rat model of post-traumatic epileptogenesis
AU - Kamnaksh, Alaa
AU - Puhakka, Noora
AU - Ali, Idrish
AU - Smith, Gregory
AU - Aniceto, Roxanne
AU - McCullough, Jesse
AU - Das Gupta, Shalini
AU - Ndode-Ekane, Xavier Ekolle
AU - Brady, Rhys
AU - Casillas-Espinosa, Pablo
AU - Hudson, Matt
AU - Santana-Gomez, Cesar
AU - Immonen, Riikka
AU - Abreu, Pedro Andrade de
AU - Jones, Nigel
AU - Shultz, Sandy
AU - Staba, Richard J.
AU - O'Brien, Terence J.
AU - Agoston, Denes
AU - Pitkänen, Asla
PY - 2019/1/1
Y1 - 2019/1/1
N2 - The Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx) is an international, multicenter, multidisciplinary study aimed at preventing epileptogenesis (EpiBioS4Rx: https://epibios.loni.usc.edu/). One of the study's major objectives is the discovery of diagnostic, prognostic, and predictive plasma protein and microRNA (miRNA) biomarkers that are sensitive, specific, and translatable to the human condition. Epilepsy due to structural brain abnormalities, secondary to neurological insults such as traumatic brain injury (TBI), currently represents ∼50% of all epilepsy cases. In the preclinical EpiBioS4Rx study, TBI was induced in adult male Sprague Dawley rats using a standardized protocol for lateral fluid-percussion injury. Whole blood was collected from the tail vein at baseline and 2, 9 and 30 days post-injury and processed for plasma separation. Biomaterial properties, sample preparation and integrity, and choice of analysis platform can significantly impact measured marker levels and, in turn, interpretation with respect to injury and/or other variables. We present here the results of procedural harmonization for the first 320 rats included in the EpiBioS4Rx study study, from three international research centers, and preliminary proteomic and miRNA analyses. We also discuss experimental considerations for establishing rigorous quality controls with the goal of harmonizing operating procedures across study sites, and delivering high-quality specimens for preclinical biomarker discovery in a rat model of post-traumatic epilepsy (PTE).
AB - The Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx) is an international, multicenter, multidisciplinary study aimed at preventing epileptogenesis (EpiBioS4Rx: https://epibios.loni.usc.edu/). One of the study's major objectives is the discovery of diagnostic, prognostic, and predictive plasma protein and microRNA (miRNA) biomarkers that are sensitive, specific, and translatable to the human condition. Epilepsy due to structural brain abnormalities, secondary to neurological insults such as traumatic brain injury (TBI), currently represents ∼50% of all epilepsy cases. In the preclinical EpiBioS4Rx study, TBI was induced in adult male Sprague Dawley rats using a standardized protocol for lateral fluid-percussion injury. Whole blood was collected from the tail vein at baseline and 2, 9 and 30 days post-injury and processed for plasma separation. Biomaterial properties, sample preparation and integrity, and choice of analysis platform can significantly impact measured marker levels and, in turn, interpretation with respect to injury and/or other variables. We present here the results of procedural harmonization for the first 320 rats included in the EpiBioS4Rx study study, from three international research centers, and preliminary proteomic and miRNA analyses. We also discuss experimental considerations for establishing rigorous quality controls with the goal of harmonizing operating procedures across study sites, and delivering high-quality specimens for preclinical biomarker discovery in a rat model of post-traumatic epilepsy (PTE).
KW - Case report form
KW - Common data elements
KW - Post-traumatic epilepsy
KW - Quality control
KW - Standardization
KW - Traumatic brain injury
UR - http://www.scopus.com/inward/record.url?scp=85058192121&partnerID=8YFLogxK
U2 - 10.1016/j.eplepsyres.2018.11.009
DO - 10.1016/j.eplepsyres.2018.11.009
M3 - Article
AN - SCOPUS:85058192121
VL - 149
SP - 92
EP - 101
JO - Epilepsy Research
JF - Epilepsy Research
SN - 0920-1211
ER -