COMPUTATIONAL TOOLS 83
Other diagrammatic simulations of complex cell networks use tools such as the Diagrammatic Cell
Language (DCL) and Visual Cell. These software tools are designed to read, query, and edit cell path-
ways, and to visualize data in a pathway context. Visual Cell creates detailed drawings by compactly
formatting thousands of molecular interactions. The software uses DCL, which can visualize and simu-
late large-scale networks such as interconnected signal transduction pathways and the gene expression
networks that control cell proliferation and apoptosis. DCL can visualize millions of chemical states and
chemical reactions.
A second approach to diagrammatic simulation has been developed by Efroni et al.^70 These re-
searchers use the visual language of Statecharts, which makes specification of the simulation precise,
legible, and machine-executable. Behavior in Statecharts is described by using states and events that
cause transitions between states. States may contain substates, thus enabling description at multiple
levels and zooming in and zooming out between levels. States may also be divided into orthogonal
states, thus modeling concurrency, allowing the system to reside simultaneously in several different
states. A cell, for example, may be described orthogonally as expressing several receptors, no receptors,
or any combination of receptors at different stages of the cell cycle and in different anatomical compart-
ments. Furthermore, transitions take the system from one state to another. In cell modeling, transitions
are the result of biological processes or the result of user intervention. A biological process may be the
result of an interaction between two cells or between a cell and various molecules. Statecharts provide
a controllable way to handle the enormous dataset of cell behavior by enabling the separation of that
dataset into orthogonal states and allowing transitions.
Still another kind of graphical interface is used for molecular visualization. Interesting biomolecules
usually consist of thousands of atoms. A list of atomic coordinates is useful for some purposes, but an
actual image of the molecule can often provide much more insight into its properties—and an image
that can be manipulated (e.g., viewed from different angles) is even more useful. Virtual reality tech-
niques can be used to provide the viewer with a large field of view, and to enable the viewer to interact
with the virtual molecule and compare it to other molecules. However, many problems in biomolecular
visualization tax the capability of current systems because of the diversity of operations required and
because many operations do not fit neatly into the current architectural paradigm.
4.3.2 Tangible Physical Interfaces,
As useful as graphical visualizations are, even in simulated three-dimensional virtual reality
they are still two-dimensional. Tangible, physical models that a human being can manipulate di-
rectly with his or her hands are an extension of the two-dimensional graphical environment. A
project at the Molecular Graphics Laboratory at the Scripps Research Institute is developing tan-
gible interfaces for molecular biology.^71 These interfaces use computer-driven autofabrication tech-
nology (i.e., three-dimensional printers) and result in physical molecular representations that one
can hold in one’s hand.
These efforts have required the development and testing of software for the representation of
physical molecular models to be built by autofabrication technologies, linkages between molecular
descriptions and computer-aided design and manufacture approaches for enhancing the models with
additional physical characteristics, and integration of the physical molecular models into augmented-
reality interfaces as inputs to control computer display and interaction.
(^70) S. Efroni, D. Harel, and I.R. Cohen, “Toward Rigorous Comprehension of Biological Complexity: Modeling, Execution, and
Visualization of Thymic T-Cell Maturation,” Genome Research 13(11):2485-2497, 2003.
(^71) A. Gillet, M. Sanner, D. Stoffler, D. Goodsell, and A. Olson, “Augmented Reality with Tangible Auto-Fabricated Models for
Molecular Biology Applications,” Proceedings of the IEEE Visualization 2004 (VIS’04), October 10-15, 2004, Austin, pp. 235-242.