Butchy, Adam
(2024)
Automated and Manual Assembly of Computational Models for Biological Systems: Applications to Macrophage Activation and CAR-T cells.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Development and updating of computational models representing complex biological systems and processes is extremely challenging. Researchers today have access to vast sets of information about molecular entities and interactions, through querying public databases, examining published models, and extracting content from literature using machine reading engines. It is the sheer vastness of this available data that has inspired systems and computational biologists to endeavor to automate the process of model creation and extension. In this work, we quantify the complexity and combinatoric-nature of true automated model assembly. We discuss how current modelers make assumptions and simplifications that change an impossible, intractable problem into one that modern computers can begin to solve. From fully automated assembly, we transition to semi-automated model assembly and extension, in which we discuss how the combinatoric nature of graph problems becomes more difficult when simulating a dynamic system and how rudimentary error functions are more likely to find local minima than global solution. Finally, two human-curated models are presented: one of macrophage priming, activation, and communication; and another of T cell-antibody-tumor cell ternary body formation. Taken together, this dissertation presents a holistic perspective on the current challenges and advances in the field of automated, semi-automated, and human-curated model assembly with applications in biological systems.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
3 June 2024 |
| Date Type: |
Publication |
| Defense Date: |
15 May 2023 |
| Approval Date: |
3 June 2024 |
| Submission Date: |
25 January 2023 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
183 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
Swanson School of Engineering > Bioengineering |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Draft |
| Date Deposited: |
03 Jun 2024 14:38 |
| Last Modified: |
03 Jun 2024 14:38 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/44135 |
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