We describe the development and implementation of a Physiological and Anatomical Visual Analytics tool (PAVA), a web browser-based application, used to visualize experimental/simulated chemical time-course data (dosimetry), epidemiological data and Physiologically-Annotated Data (PAD). Using continuous color mapping scheme both spatial (organ shape and location) and temporal (time-course/kinetics) data was cast onto an abstract, layered, 2D visual representation of the human anatomy and physiology. This approach is aligned with the compartment-level of detail afforded by Physiologically-Based Pharmacokinetic (PBPK) modeling of chemical disposition. In this tutorial we provide several illustrative examples of how PAVA may be applied: (1) visualization of multiple organ/tissue simulated dosimetry of a previously published oral exposure route ethanol PBPK model, (2) visualization of PAD such as organ-specific disease time-lines or (3) tissue-specific mRNA expression-level profiles (e.g. phase I/II metabolic enzymes and nuclear receptors) to draw much needed molecular biological conclusions at organ-level resolution conducive to model development. Furthermore, discussion is raised on how graphical representations of PBPK models, and the use of PAVA more generally to visualize PAD, can be of benefit. We believe this novel platform-independent tool for visualizing PAD on physiologically-relevant representations of human anatomy will become a valuable visual analytic addition to the tool-kits of modern exposure scientists, computational biologists, toxicologists, biochemists, molecular biologists, epidemiologists and pathologists alike in visually translating, representing and mining complex PAD relationships required to understand systems biology or manage chemical risk.
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Wildstrom S (2003) A picture is worth a thousand charts: new software “visualizes” data in ways that give a much richer image than typical tools. Bus Week. http://www.businessweek.com/magazine/content/03_03/b3816045.htm. Accessed 20 Jan 2003
Nichols J, Rheingans P, Lothebach D, McGeachie R, Skow L, McKim J (1994) Three-dimensional visualization of physiologically based kinetic model outputs. Environ Health Perspect 102(11):952
Yoshikawa Y, Sone H, Yoshikawa H, Takada K (1999) WinPBPK—a software for physiologically-based pharmacokinetic model analysis: application to tissue and organ distribution analysis of tacrolimus. Drug Metab Pharmacokinet 14(1):22–31
Lawton G (2009) Users take a close look at visual analytics. Computer 42(2):19–22
Viegas FB, Wattenberg M, van Ham F, Kriss J, McKeon M (2007) Manyeyes: a site for visualization at internet scale. IEEE Trans Vis Comput Graph 13(6):1121–1128
Blancato JN, Power FW, Brown RN, Dary CC (2006) Exposure related dose estimating model (ERDEM) a physiologically-based pharmacokinetic and pharmacodynamic (PBPK/PD) model for assessing human exposure and risk. EPA/600/R-06/061
Levitt DG (2009) PKQuest_Java: free, interactive physiologically based pharmacokinetic software package and tutorial. BMC Res Notes 2(1):158
Levitt DG (2002) 1: PKQuest: measurement of intestinal absorption and first pass metabolism—application to human ethanol pharmacokinetics. BMC Clin Pharmacol 2:4
Bourne DWA (1989) BOOMER, a simulation and modeling program for pharmacokinetic and pharmacodynamic data analysis. Comput Methods Programs Biomed 29:191–195
Cahill T, Cousins I, Mackay D (2003) Development and application of a generalized physiologically based pharmacokinetic model for multiple environmental contaminants. Environ Toxicol Chem 22(1):26–34
Smith T, Petoussi-Henss N, Zankl M (2000) Comparison of internal radiation doses estimated by MIRD and voxel techniques for a “family” of phantoms. Eur J Nucl Med Mol Imaging 27(9):1387–1398
Weinstein S (1993) Magic images via Imagemagick. The C Users J 11(10):93–102
Nishimura M, Naito S, Yokoi T (2004) Tissue-specific mRNA expression profiles of nuclear receptor superfamily. Drug Metab Pharmacokinet 19(2):135–149
Nishimura M, Hiroshi Y, Yoshitsugu H, Naito S, Satoh T (2003) Tissue distribution of mRNA expression of human cytochrome p450 isoforms. Yakugaku Zasshi 123(5):369–375
Nishimura M, Naito S (2006) Tissue-specific mRNA expression profiles of human phase 1 metabolizing enzymes except for cytochrome p450 and phase II metabolizing enzymes. Drug Metab Pharmacokinet 21(5):357–374
US Mortality Data 1960–2005, US Mortality Volumes 1930–1959 (2008) National Center for Health Statistics, Centers for Disease Control and Prevention. http://www.cancer.org/downloads/PRO/Cancer_Statistic_2009_Slides_rev.ppt
Ankley G, Denslow N, Watanabe K (2009) A computational model of the hypothalamic-pituitary-gonadal axis in male fathead minnows exposed to 17α-ethinylestradiol and 17β-estradiol. Toxicol Sci 109(2):180–192
The authors gratefully acknowledge Rachael Brady (Duke University Visual Technology Group) for providing the opportunity to present to the academic visualization community and receive insightful feedback (see http://vis.duke.edu/FridayForum/09Fall.html and http://lectopia.oit.duke.edu/ilectures/ilectures.lasso?ut=193&id=21022) and Dr. Shane Peterson and Dr. Elin Ulrich (US-EPA) for thorough criticism and suggestions towards the manuscript.
This manuscript was approved by the U.S. EPA’s National Exposure Research Laboratory for publication. However, the contents do not necessarily reflect the views and policies of the EPA and mention of trade names or commercial products does not constitute endorsement or recommendation for use. Each of the authors declares no competing interests pertaining to the present work.
Electronic supplementary material
Supporting Information. Information regarding PAVA v1.0 development and the server-side PAVA v1.0 application installation files can be obtained on the HEASD product/tools website in the “Models” section at http://www.epa.gov/heasd/products/products.html or under the PAVA designated page (http://www.epa.gov/heasd/products/pava/pava.html). In addition, there is product development and user forum with dialog on PAVA on the US-Environmental Protection Agency’s Environmental Science Connector (http://portal.epa.gov/ESC). Interested users may join to familiarize, comment, and learn about the PAVA development cycle and provide input for desired features in future releases by contacting the authors. Included in the supporting information are (i) a screen-capture video with dialog demonstrating how a PAVA animation may be generated (ii) animated gif rendering of Fig. 1 ethanol model and (iii) Fig. 4c—Male–Female differential cancer mortality time-course data animation. Below is the link to the electronic supplementary material.
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Goldsmith, M., Transue, T.R., Chang, D.T. et al. PAVA: physiological and anatomical visual analytics for mapping of tissue-specific concentration and time-course data. J Pharmacokinet Pharmacodyn 37, 277–287 (2010) doi:10.1007/s10928-010-9160-6
- Physiologically-annotated data
- Visual analytics
- Server-side application
- Model animation
- Concentration time-course
- Disease progression timelines
- Model rendering