Harmonization of pipeline for preclinical multicenter plasma protein and miRNA biomarker discovery in a rat model of post-traumatic epileptogenesis

Alaa Kamnaksh, Noora Puhakka, Idrish Ali, Gregory Smith, Roxanne Aniceto, Jesse McCullough, Shalini Das Gupta, Xavier Ekolle Ndode-Ekane, Rhys Brady, Pablo Casillas-Espinosa, Matt Hudson, Cesar Santana-Gomez, Riikka Immonen, Pedro Andrade de Abreu, Nigel Jones, Sandy Shultz, Richard J. Staba, Terence J. O'Brien, Denes Agoston, Asla Pitkänen

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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).

Original languageEnglish
Pages (from-to)92-101
Number of pages10
JournalEpilepsy Research
Volume149
DOIs
Publication statusPublished - 1 Jan 2019

Keywords

  • Case report form
  • Common data elements
  • Post-traumatic epilepsy
  • Quality control
  • Standardization
  • Traumatic brain injury

Cite this

Kamnaksh, Alaa ; Puhakka, Noora ; Ali, Idrish ; Smith, Gregory ; Aniceto, Roxanne ; McCullough, Jesse ; Das Gupta, Shalini ; Ndode-Ekane, Xavier Ekolle ; Brady, Rhys ; Casillas-Espinosa, Pablo ; Hudson, Matt ; Santana-Gomez, Cesar ; Immonen, Riikka ; Abreu, Pedro Andrade de ; Jones, Nigel ; Shultz, Sandy ; Staba, Richard J. ; O'Brien, Terence J. ; Agoston, Denes ; Pitkänen, Asla. / Harmonization of pipeline for preclinical multicenter plasma protein and miRNA biomarker discovery in a rat model of post-traumatic epileptogenesis. In: Epilepsy Research. 2019 ; Vol. 149. pp. 92-101.
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abstract = "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).",
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author = "Alaa Kamnaksh and Noora Puhakka and Idrish Ali and Gregory Smith and Roxanne Aniceto and Jesse McCullough and {Das Gupta}, Shalini and Ndode-Ekane, {Xavier Ekolle} and Rhys Brady and Pablo Casillas-Espinosa and Matt Hudson and Cesar Santana-Gomez and Riikka Immonen and Abreu, {Pedro Andrade de} and Nigel Jones and Sandy Shultz and Staba, {Richard J.} and O'Brien, {Terence J.} and Denes Agoston and Asla Pitk{\"a}nen",
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Kamnaksh, A, Puhakka, N, Ali, I, Smith, G, Aniceto, R, McCullough, J, Das Gupta, S, Ndode-Ekane, XE, Brady, R, Casillas-Espinosa, P, Hudson, M, Santana-Gomez, C, Immonen, R, Abreu, PAD, Jones, N, Shultz, S, Staba, RJ, O'Brien, TJ, Agoston, D & Pitkänen, A 2019, 'Harmonization of pipeline for preclinical multicenter plasma protein and miRNA biomarker discovery in a rat model of post-traumatic epileptogenesis', Epilepsy Research, vol. 149, pp. 92-101. https://doi.org/10.1016/j.eplepsyres.2018.11.009

Harmonization of pipeline for preclinical multicenter plasma protein and miRNA biomarker discovery in a rat model of post-traumatic epileptogenesis. / Kamnaksh, Alaa; Puhakka, Noora; Ali, Idrish; Smith, Gregory; Aniceto, Roxanne; McCullough, Jesse; Das Gupta, Shalini; Ndode-Ekane, Xavier Ekolle; Brady, Rhys; Casillas-Espinosa, Pablo; Hudson, Matt; Santana-Gomez, Cesar; Immonen, Riikka; Abreu, Pedro Andrade de; Jones, Nigel; Shultz, Sandy; Staba, Richard J.; O'Brien, Terence J.; Agoston, Denes; Pitkänen, Asla.

In: Epilepsy Research, Vol. 149, 01.01.2019, p. 92-101.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Kamnaksh, Alaa

AU - Puhakka, Noora

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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

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KW - Case report form

KW - Common data elements

KW - Post-traumatic epilepsy

KW - Quality control

KW - Standardization

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