Biological pathway-centric approach to integrative analysis of array data as applied to mefloquine neurotoxicity

Abhishek Soni, Jerry Jenkins, Jonathan Hood, Michael Aschner, Chin Thai Jiang, Shankar Sundaram

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Mefloquine, a potent anti-malarial therapeutic, is known to cause adverse neurological or psychiatric effects in a subset of patient population which has been reportedly linked with specific single nucleotide polymorphisms (SNPs). Development of a predictive clinical, molecular diagnostic screen capable for the a priori determination of the susceptibility of an individual to Mefloquine neurotoxicity is critical for safe administration. Towards achieving this goal, we present a novel systems-biology centered methodology, combining transcriptional profiling using primary rat cortical neurons exposed to Mefloquine and novel pathway identification/analysis tools enabling the development of a detailed intracellular pathway model to explain Mefloquine-induced neurotoxicity. Boolean methods are used to objectively down select potential SNP target candidates. The results from the proposed methodology have consistently identified PTK2B as the most likely SNP target across multiple data sets, and using multiple toxicity markers.

Original languageEnglish (US)
Title of host publication2007 AIChE Annual Meeting
StatePublished - Dec 1 2007
Externally publishedYes
Event2007 AIChE Annual Meeting - Salt Lake City, UT, United States
Duration: Nov 4 2007Nov 9 2007

Publication series

NameAIChE Annual Meeting, Conference Proceedings

Other

Other2007 AIChE Annual Meeting
CountryUnited States
CitySalt Lake City, UT
Period11/4/0711/9/07

ASJC Scopus subject areas

  • Chemical Engineering(all)
  • Chemistry(all)

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    Soni, A., Jenkins, J., Hood, J., Aschner, M., Jiang, C. T., & Sundaram, S. (2007). Biological pathway-centric approach to integrative analysis of array data as applied to mefloquine neurotoxicity. In 2007 AIChE Annual Meeting (AIChE Annual Meeting, Conference Proceedings).