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System-wide analysis of hepatotoxicological responses: tissomics is key
Journal article   Open access   Peer reviewed

System-wide analysis of hepatotoxicological responses: tissomics is key

Andres Kriete, Keith Boyce and Bradley Love
Cytometry. Part A, v 69(7), pp 612-619
Jul 2006
PMID: 16680687
url
https://doi.org/10.1002/cyto.a.20282View
Published, Version of Record (VoR)Maybe Open Access (Publisher Bronze) Open

Abstract

Animals Confidence Intervals Gene Expression Profiling - methods Gene Expression Profiling - statistics & numerical data Genetic Markers Hepatocytes - drug effects Hepatocytes - metabolism Hepatocytes - pathology Liver - drug effects Liver - metabolism Liver - pathology Male Rats Rats, Sprague-Dawley Systems Biology - methods Systems Biology - statistics & numerical data Toxicity Tests - methods Toxicity Tests - statistics & numerical data Xenobiotics - toxicity
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. 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. 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. 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.

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Collaboration types
Domestic collaboration
Web of Science research areas
Biochemical Research Methods
Cell Biology
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