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 publicationAIChE Annual Meeting, Conference Proceedings
StatePublished - 2007
Externally publishedYes
Event2007 AIChE Annual Meeting - Salt Lake City, UT, United States
Duration: Nov 4 2007Nov 9 2007

Other

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

Fingerprint

Mefloquine
Nucleotides
Polymorphism
Neurons
Toxicity
Rats
Antimalarials

ASJC Scopus subject areas

  • Chemical Engineering(all)
  • Chemistry(all)

Cite this

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 AIChE Annual Meeting, Conference Proceedings

Biological pathway-centric approach to integrative analysis of array data as applied to mefloquine neurotoxicity. / Soni, Abhishek; Jenkins, Jerry; Hood, Jonathan; Aschner, Michael; Jiang, Chin Thai; Sundaram, Shankar.

AIChE Annual Meeting, Conference Proceedings. 2007.

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

Soni, A, Jenkins, J, Hood, J, Aschner, M, Jiang, CT & Sundaram, S 2007, Biological pathway-centric approach to integrative analysis of array data as applied to mefloquine neurotoxicity. in AIChE Annual Meeting, Conference Proceedings. 2007 AIChE Annual Meeting, Salt Lake City, UT, United States, 11/4/07.
Soni A, Jenkins J, Hood J, Aschner M, Jiang CT, Sundaram S. Biological pathway-centric approach to integrative analysis of array data as applied to mefloquine neurotoxicity. In AIChE Annual Meeting, Conference Proceedings. 2007
Soni, Abhishek ; Jenkins, Jerry ; Hood, Jonathan ; Aschner, Michael ; Jiang, Chin Thai ; Sundaram, Shankar. / Biological pathway-centric approach to integrative analysis of array data as applied to mefloquine neurotoxicity. AIChE Annual Meeting, Conference Proceedings. 2007.
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