Machine learning based analyses on metabolic networks supports high-throughput knockout screens

BACKGROUND: Computational identification of new drug targets is a major goal of pharmaceutical bioinformatics. RESULTS: This paper presents a machine learning strategy to study and validate essential enzymes of a metabolic network. Each single enzyme was characterized by its local network topology, gene homologies and co-expression, and flux balance analyses. A machine learning system was trained to distinguish between essential and non-essential reactions. It was validated by a comprehensive experimental dataset, which consists of the phenotypic outcomes from single knockout mutants of Escherichia coli (KEIO collection). We yielded very reliable results with high accuracy (93%) and precision (90%). We show that topologic, genomic and transcriptomic features describing the network are sufficient for defining the essentiality of a reaction. These features do not substantially depend on specific media conditions and enabled us to apply our approach also for less specific media conditions, like the lysogeny broth rich medium. CONCLUSION: Our analysis is feasible to validate experimental knockout data of high throughput screens, can be used to improve flux balance analyses and supports experimental knockout screens to define drug targets.