title: Mode of action classification of chemicals using multi-concentration time-dependent cellular response profiles.
abstract: In this paper, we present a new statistical pattern recognition method for classifying cytotoxic cellular responses to toxic agents. The advantage of the proposed method is to quickly assess the toxicity level of an unclassified toxic agent on human health by bringing cytotoxic cellular responses with similar patterns (mode of action, MoOA) into the same class. The proposed method is a model-based hierarchical classification approach incorporating principal component analysis (PCA) and functional data analysis (FDA). The cytotoxic cell responses are represented by multi-concentration time-dependent cellular response profiles (TCRPs) which are dynamically recorded by using the xCELLigence real-time cell analysis high-throughput (RTCA HT) system. The classification results obtained using our algorithm show satisfactory discrimination and are validated using biological facts by examining common chemical mechanisms of actions with treatment on human hepatocellular carcinoma cells (HepG2).
authors.affiliation: Department of Chemicals & Materials Engineering, University of Alberta, Edmonton, Alberta T6G 2G6, Canada. Electronic address: zhankun@ualberta.ca.
authors.forename: Zhankun
authors.initials: Z
authors.lastname: Xi
authors.affiliation: Department of Chemicals & Materials Engineering, University of Alberta, Edmonton, Alberta T6G 2G6, Canada. Electronic address: khare@ualberta.ca.
authors.forename: Swanand
authors.initials: S
authors.lastname: Khare
authors.affiliation: Department of Chemicals & Materials Engineering, University of Alberta, Edmonton, Alberta T6G 2G6, Canada. Electronic address: acheung1@ualberta.ca.
authors.forename: Aaron
authors.initials: A
authors.lastname: Cheung
authors.affiliation: Department of Chemicals & Materials Engineering, University of Alberta, Edmonton, Alberta T6G 2G6, Canada. Electronic address: biao.huang@ualberta.ca.
authors.forename: Biao
authors.initials: B
authors.lastname: Huang
authors.affiliation: Department of Chemicals & Materials Engineering, University of Alberta, Edmonton, Alberta T6G 2G6, Canada; School of Electrical & Information Engineering, Jiangsu University, Zhenjiang, Jiangsu 212013, China. Electronic address: thpan@ujs.edu.cn.
authors.forename: Tianhong
authors.initials: T
authors.lastname: Pan
authors.affiliation: Alberta Health, Edmonton, Alberta T5J 1S6, Canada. Electronic address: weiping.zhang@gov.ab.ca.
authors.forename: Weiping
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Chemicals & Materials Engineering, University of Alberta, Edmonton, Alberta T6G 2G6, Canada. Electronic address: fibrahim@ualberta.ca.
authors.forename: Fadi
authors.initials: F
authors.lastname: Ibrahim
authors.affiliation: Department of Biology, ACEA Biosciences, San Diego, CA 92121, USA. Electronic address: cjin@aceabio.com.
authors.forename: Can
authors.initials: C
authors.lastname: Jin
authors.affiliation: Alberta Health, Edmonton, Alberta T5J 1S6, Canada. Electronic address: stephan.gabos@gov.ab.ca.
authors.forename: Stephan
authors.initials: S
authors.lastname: Gabos
mesh_terms: D000465:Algorithms; D000970:Antineoplastic Agents / Q000737:chemistry / Q000145:classification* / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D016000:Cluster Analysis; D056945:Hep G2 Cells; D006801:Humans; D025341:Principal Component Analysis; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents
keywords: Functional data analysis; Hierarchical classification; Mode of action; Principal component analysis; Time-dependent cellular response profiles