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Hybrid metabolic network completion

  • CLÉMENCE FRIOUX (a1), TORSTEN SCHAUB (a2) (a3), SEBASTIAN SCHELLHORN (a4), ANNE SIEGEL (a5) and PHILIPP WANKO (a6)...
Abstract

Metabolic networks play a crucial role in biology since they capture all chemical reactions in an organism. While there are networks of high quality for many model organisms, networks for less studied organisms are often of poor quality and suffer from incompleteness. To this end, we introduced in previous work an answer set programming (ASP)-based approach to metabolic network completion. Although this qualitative approach allows for restoring moderately degraded networks, it fails to restore highly degraded ones. This is because it ignores quantitative constraints capturing reaction rates. To address this problem, we propose a hybrid approach to metabolic network completion that integrates our qualitative ASP approach with quantitative means for capturing reaction rates. We begin by formally reconciling existing stoichiometric and topological approaches to network completion in a unified formalism. With it, we develop a hybrid ASP encoding and rely upon the theory reasoning capacities of the ASP system clingo for solving the resulting logic program with linear constraints over reals. We empirically evaluate our approach by means of the metabolic network of Escherichia coli. Our analysis shows that our novel approach yields greatly superior results than obtainable from purely qualitative or quantitative approaches.

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This work was partially funded by DFG grant SCHA 550/9 and 11 and benefited from the support of the French Government via the National Research Agency investment expenditure program IDEALG ANR-10-BTBR-04.

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Theory and Practice of Logic Programming
  • ISSN: 1471-0684
  • EISSN: 1475-3081
  • URL: /core/journals/theory-and-practice-of-logic-programming
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