System-wide analysis of hepatotoxicological responses: Tissomics is key

Authors

  • Andres Kriete,

    Corresponding author
    1. Icoria Inc., Pittsburgh, Pennsylvania
    2. School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, Pennsylvania
    3. Coriell Institute, Camden, New Jersey
    • Associate Professor for Bioinformation Engineering, Drexel University & Coriell Bioinformatics Initiative, School of Biomedical Engineering, Science and Health System, Drexel University, Philadelphia, PA 19104, USA
    Search for more papers by this author
  • Keith Boyce,

    1. Icoria Inc., Pittsburgh, Pennsylvania
    2. Immune Tolerance Network, Pittsburgh, Pennsylvania
    Search for more papers by this author
  • Bradley Love

    1. Invitrogen Corp., Carlsbad, California
    Search for more papers by this author

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

Ancillary