Professional Documents
Culture Documents
Creating A Biologist-Oriented Interface and Code Generation System For A Computational Modeling Assistant
Creating A Biologist-Oriented Interface and Code Generation System For A Computational Modeling Assistant
Jonathan M. Matthews1, Scott Christley2, Ph.D. and Gary An2, M.D. 1Massachusetts Institute of Technology, Cambridge, MA; 2University of Chicago, Chicago, IL
Abstract
We have previously developed an artificial intelligence system, the Computational Modeling Assistant (CMA), that augments the construction of dynamic computational models from biological conceptual models. To further reduce the threshold for the use of computational methods, we aim to develop a user-friendly interface that allows biologists to interact with the CMA and generate a computational model without the need for programming expertise.
Biologist-Oriented Interface
Biomedical researchers express their conceptual models through natural language. They describe the biological entities, process and interactions with a series of declarative statements.
The CMA uses a logical framework based on rewriting logic to reason about biological processes and translate them into computation constructs.
Accepts near-natural language statements about biological entities and concepts. Utilizes ontologies to ascribe semantic context to nouns and verbs in biological statements. Contains a set of logical rewrite rules that maps biological concepts into computational modeling methods. Supports multiple modeling methods such as ODEs, PDEs, Petri nets and agent-based models.
A biological conceptual model of Pseudomonas aeruginosa virulence activation. A series of statements describes the gene, mRNA, proteins and small molecules, and processes such as protein/ small molecule binding and transcriptional regulation.
HTML and CSS were used to create the GUI, jQuery, a JavaScript library, was used to handle client scripting, PHP was used for server-side scripting, and PostgreSQL was used for the database.
System Architecture
The CMA interface utilizes a three-tier architecture: a web-based graphical user interface (GUI) for the researcher to input biological conceptual models, a client- and server-side scripting system to manage models and run the back-end logic code, and a database system to store knowledge for future use.
description to be provided to the user about how the biological model was transformed
S. Christley, G. An
into a computational model, which might be useful for pedagogical or debugging 17. LecA is transcribed [SBO:0000183] into PA-I lectin mRNA purposes. For the biological model given in Figure 4, the CMA produces the model 18. PA-I lectin mRNA is translated [SBO:0000184] into PA-I lectin 19 specification PA-I lectin mRNA decays of eight ODEs and specification show in Figure 6. This model is composed 20. Pseudomonas secretes [GO:0030528] PA-I lectin into extracellular compartment three PDEs represented by these equations: [GO:0005615].
d[ muc2 mRNA ] = H ( muc2 gene ) dt d[ muc2] = H ( muc2 mRNA ) ! S ( muc2) dt d[ AmRNA ] = H ( Agene ) dt d[ A ] = H ( AmRNA ) ! B( A, B) dt d[ BmRNA ] = H ( Bgene ) dt d[ B ] = H ( BmRNA ) ! B( A, B) dt d[ AB] = B( A, B) ! S ( AB) dt d[ muc2 E ] = S ( muc2) dt d[ AE ] = " 2 AE + D( AB) ! k1 AE dt d[ BE ] = " 2 BE + D( AB) ! k2 BE dt d[ ABE ] = " 2 ABE + S ( AB) ! D( ABE ) dt
PDE model
As in the process delineated above, the virulence pathway biological model was presented to the CMA, translated into a set of Maude logical statements, and then the application of the Maude logical rewrite rules shown in Fig. 7 produced a Petri net model. The resulting model is shown in Fig. 8. It should be noted that an additional output of this process was an error statement: polypeptide chain entities OprF, interferon-gamma, RhlRI, has no translate This statement resulted from the fact that some of the entities listed in the biological model did not have a rule leading to their production. However, rather than considering this error statement as rendering the biological model invalid, these entities would be presented back to the researcher as variables in the model that require initialization values; i.e. the input values for simulation execution. The above model specication can be described in standard notation for biochemical rules:
Web-based GUI
PA-I-lectin-mRNA PA-I-lectin-mRNA PA-I-lectin interferon-OprF-complex interferon-OprF-complex RhlRI-Lux-box-complex where H, S, B and D are the hillFunction, secreteFunction, bindFunction and OprF + interferon-gamma dissociateFunction functions. Lux-box + RhlRI lecA + RhlRI-Lux-box-complex Model Parameters
PA-I-lectin-mRNA + PA-I-lectin PA-I-lectin[e] interferon-OprF-complex + RhlRI Lux-box + RhlRI interferon-OprF-complex RhlRI-Lux-box-complex lecA + RhlRI-Lux-box-complex + PA-I-lectin-mRNA
Management of Knowledgebase
The GUI provides management of CMAs knowledgebase of modeling methods and mapping rules, and allows the knowledgebase to be extended to support new methods and new biological concepts.
CMA uses an internal XML format for model specification (BioSwarm simulation system), but compatible models can be provided in standard formats such as SBML.
As with the gut mucus model example, the conversion of the base Petri net model In our example for gut mucus stratification, the model specification uses generic names into simulation code would involve a selection by the researcher among a set of for various interaction functions such as subcategories hillFunction, of bindFunction, etc. However, these properties, such as deterministic Petri nets based on their specic stochastic, and the of the system under study. Furthermore, as defunctions can be defined in more detail, or allowing the CMA tocharacteristics perform additional scribed in Example #1, the CMA could also have generated an ODE model of the modeling and simulation capabilities. For example, the CMA could query the number and virulence activation pathway; in practice, the biological model of virulence activation would have been inputted into the CMA and both a Petri net and an ODE model (among, perhaps, other types) would be generated, each with suggested parameters based on the requirements of the particular modeling method, and the researcher would select one or the other (or perhaps even both) based on the initialization data available or the desired dynamics to be investigated. Additionally, future development of the CMA would include the capability to parse the biological model and
Modeling Methods Mapping Rules