Genome and metabolome: chance and necessity

• Published in: Genome Biology Vol. 22; no. 1; p. 276
• Main Authors: Gonçalves, Emanuel, Frezza, Christian
• Format: Journal Article
• Language: English
• Published: England BioMed Central 23-09-2021; BMC
• Subjects: Cancer; CRISPR; Environmental conditions; Evolution; Genome, Human; Genomes; Genomics; Genotype & phenotype; Human Genome Project; Humans; Hypotheses; Mathematical models; Metabolic networks; Metabolism; Metabolites; Metabolome; Metabolomics; Mitochondrial DNA; Mutation; Neoplasms - genetics; Neoplasms - metabolism; Proteomics; Tumorigenesis; Tumors
• ISSN: 1474-760X; 1474-7596; 1474-760X
• DOI: 10.1186/s13059-021-02501-0

[...]to a simple accumulation or combination of key “driver” mutations, oncogenesis might be driven by the interplay between the availability of healthy cells harbouring oncogenic mutations along with permissive selective pressures. With the advent of the human genome project and technological breakthroughs, cancer genomes are now routinely sequenced, enabling the systematic characterization of somatic genetic alterations observed in thousands of cancers. [...]genome-wide CRISPR-Cas9 screens unveiled the importance of the metabolic milieu in determining genetic dependencies and the same cell line in different metabolic contexts displays > 5% significant differential gene dependencies [10]. An example of this is genome-scale metabolic models, which provide an integrative framework to tailor metabolic networks to specific tissues or single cells using genomics, transcriptomics and proteomics datasets [14]. [...]the mathematical representation of the metabolic network enables scalable simulations of the metabolic fluxes and to predict the impact of genetic metabolic perturbations as well as alterations in metabolic environmental conditions.