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System‐wide analysis of hepatotoxicological responses: Tissomics is key
Author(s) -
Kriete Andres,
Boyce Keith,
Love Bradley
Publication year - 2006
Publication title -
cytometry part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.316
H-Index - 90
eISSN - 1552-4930
pISSN - 1552-4922
DOI - 10.1002/cyto.a.20282
Subject(s) - computer science , computational biology , data science , biology
Abstract Background: Combining diverse data streams across different levels of biological observation, such as molecular, cellular, and clinical chemistry responses, support a system‐wide diagnostic approach. Recent progress in slide‐based cytometry contributes to the development of tissomics, a high‐throughput and high‐content phenotyping methodology that provides data‐rich profiles of cellular heterogeneity in tissues enabling correlative statistical treatments over multiple scales of biological hierarchies. Methods: Phenotypical data are covariants that can be used as biomarkers to identify relevant candidate genes by associating initiating molecular events with phenotypical changes and adverse outcomes. We introduce a procedure of combined statistical and analytical tools to identify and visualize such associations for nonpooled entities. The new utility is applied to a time‐controlled, low‐dose toxicological study including a control and two xenobiotic compounds. Results: An integrated analysis identified specific molecular and phenotypical biomarkers, which support the classification of animals in the absence of any visual indicators from pathology readings. Discussion: The introduction of controlled perturbations to tissues provides a prototypical setting to develop a sensitive, systems‐based analysis methodology suitable for a broader range of biomedical applications. © 2006 International Society for Analytical Cytology