Genome-scale gene/reaction essentiality and synthetic lethality analysis

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

Synthetic lethals are to pairs of non-essential genes whose simultaneous deletion prohibits growth. One can extend the concept of synthetic lethality by considering gene groups of increasing size where only the simultaneous elimination of all genes is lethal, whereas individual gene deletions are not. We developed optimization-based procedures for the exhaustive and targeted enumeration of multi-gene (and by extension multi-reaction) lethals for genome-scale metabolic models. Specifically, these approaches are applied to iAF1260, the latest model of Escherichia coli, leading to the complete identification of all double and triple gene and reaction synthetic lethals as well as the targeted identification of quadruples and some higher-order ones. Graph representations of these synthetic lethals reveal a variety of motifs ranging from hub-like to highly connected subgraphs providing a birds-eye view of the avenues available for redirecting metabolism and uncovering complex patterns of gene utilization and interdependence. The procedure also enables the use of falsely predicted synthetic lethals for metabolic model curation. By analyzing the functional classifications of the genes involved in synthetic lethals, we reveal surprising connections within and across clusters of orthologous group functional classifications.

Original languageEnglish (US)
Article number301
JournalMolecular Systems Biology
Volume5
DOIs
StatePublished - Jan 20 2009

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lethal genes
Genome
Genes
Gene
genome
genes
Lethal Genes
Synthetic Genes
Deletion
Gene Deletion
taxonomy
synthetic genes
gene deletion
Quadruple
Graph Representation
Synthetic Lethal Mutations
Escherichia coli
Metabolism
Enumeration
Escherichia Coli

All Science Journal Classification (ASJC) codes

  • Medicine(all)
  • Information Systems
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Computational Theory and Mathematics
  • Applied Mathematics

Cite this

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Genome-scale gene/reaction essentiality and synthetic lethality analysis. / Suthers, Patrick; Zomorrodi, Alireza; Maranas, Costas D.

In: Molecular Systems Biology, Vol. 5, 301, 20.01.2009.

Research output: Contribution to journalArticle

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