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LGEM+: A First-Order Logic Framework for Automated Improvement of Metabolic Network Models Through Abduction
Chalmers University of Technology, Gothenburg, Sweden.
The University of Manchester, Manchester, UK.
Chalmers University of Technology, Gothenburg, Sweden.
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Industrial Biotechnology. Chalmers University of Technology, Gothenburg, Sweden.ORCID iD: 0000-0002-0408-3515
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2023 (English)In: Discovery Science - 26th International Conference, DS 2023, Proceedings, Springer Nature , 2023, p. 628-643Conference paper, Published paper (Refereed)
Abstract [en]

Scientific discovery in biology is difficult due to the complexity of the systems involved and the expense of obtaining high quality experimental data. Automated techniques are a promising way to make scientific discoveries at the scale and pace required to model large biological systems. A key problem for 21st century biology is to build a computational model of the eukaryotic cell. The yeast Saccharomyces cerevisiae is the best understood eukaryote, and genome-scale metabolic models (GEMs) are rich sources of background knowledge that we can use as a basis for automated inference and investigation. We present LGEM+, a system for automated abductive improvement of GEMs consisting of: a compartmentalised first-order logic framework for describing biochemical pathways (using curated GEMs as the expert knowledge source); and a two-stage hypothesis abduction procedure. We demonstrate that deductive inference on logical theories created using LGEM+, using the automated theorem prover iProver, can predict growth/no-growth of S. cerevisiae strains in minimal media. LGEM+ proposed 2094 unique candidate hypotheses for model improvement. We assess the value of the generated hypotheses using two criteria: (a) genome-wide single-gene essentiality prediction, and (b) constraint of flux-balance analysis (FBA) simulations. For (b) we developed an algorithm to integrate FBA with the logic model. We rank and filter the hypotheses using these assessments. We intend to test these hypotheses using the robot scientist Genesis, which is based around chemostat cultivation and high-throughput metabolomics.

Place, publisher, year, edition, pages
Springer Nature , 2023. p. 628-643
Keywords [en]
artificial intelligence, automated theorem proving, first-order logic, metabolic modelling, Scientific discovery, systems biology
National Category
Bioinformatics (Computational Biology) Bioinformatics and Computational Biology Computer Sciences
Identifiers
URN: urn:nbn:se:kth:diva-338987DOI: 10.1007/978-3-031-45275-8_42Scopus ID: 2-s2.0-85174317371OAI: oai:DiVA.org:kth-338987DiVA, id: diva2:1808746
Conference
26th International Conference on Discovery Science, DS 2023, Porto, Portugal, Oct 9 2023 - Oct 11 2023
Note

Part of ISBN 9783031452741

QC 20231101

Available from: 2023-11-01 Created: 2023-11-01 Last updated: 2025-02-05Bibliographically approved

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Tiukova, Ievgeniia A.

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