Object-Oriented Specification of Complex Bio-computing Processes: A Case Study of a Network of Proteolytic Enzymes

We propose a case study where a familiar but very complex and intrinsically woven bio-computing system – the blood clotting cascade – is specified using methods from software design known as object-oriented design (OOD). The specifications involve definition and inheritance of classes and methods and use design techniques from the most widely used OOD-language: the Unified Modeling Language (UML), as well as its Real-Time-UML extension.First, we emphasize the needs for a unified methodology to specify complex enough biological and biochemical processes. Then, using the blood clotting cascade as a example, we define the class diagrams which exhibit the static structure of procoagulant factors of proenzyme-enzyme conversions, and finally we give a dynamic model involving events, collaboration, synchronization and sequencing. We thus show that OOD can be used in fields very much beyond software design, gives the benefit of unified and sharable descriptions and, as a side effect, automatic generation of code templates for simulation software.

[1]  Ivar Jacobson,et al.  The Unified Modeling Language User Guide , 1998, J. Database Manag..

[2]  Bruce Powell Douglass,et al.  Real-time UML (2nd ed.): developing efficient objects for embedded systems , 1997 .

[3]  K Fujikawa,et al.  The coagulation cascade: initiation, maintenance, and regulation. , 1991, Biochemistry.

[4]  R. Chambers,et al.  Coagulation cascade proteases and tissue fibrosis. , 2001, Biochemical Society transactions.

[5]  Bruce Powel Douglass Real-Time UML , 2002, FTRTFT.

[6]  Paul Woolley,et al.  Mechanisms in blood coagulation fibrinolysis and the complement system , 1991 .

[7]  S. D. Kimball,et al.  Thrombin active site inhibitors. , 1995, Bioorganic & medicinal chemistry.

[8]  G. Broze,et al.  Tissue factor pathway inhibitor and the revised theory of coagulation. , 1995, Annual review of medicine.

[9]  Kendall Scott,et al.  UML distilled - a brief guide to the Standard Object Modeling Language (2. ed.) , 2000, notThenot Addison-Wesley object technology series.

[10]  Barbara Liskov,et al.  Keynote address - data abstraction and hierarchy , 1988, OOPSLA '87.

[11]  Amir Pnueli,et al.  Formal Modeling of C. elegans Development: A Scenario-Based Approach , 2003, CMSB.

[12]  Barbara Liskov,et al.  Data Abstraction and Hierarchy , 1987 .

[13]  M. Boffa,et al.  A Study of the Mechanism of Inhibition of Fibrinolysis by Activated Thrombin-activable Fibrinolysis Inhibitor* , 1998, The Journal of Biological Chemistry.

[14]  Jozef Arnout,et al.  Anti-factor VIII antibodies of hemophiliac patients are frequently directed towards nonfunctional determinants and do not exhibit isotypic restriction. , 1993 .