A multimodal atlas of tumour metabolism reveals the architecture of gene-metabolite covariation. Review uri icon

Overview

abstract

  • Tumour metabolism is controlled by coordinated changes in metabolite abundance and gene expression, but simultaneous quantification of metabolites and transcripts in primary tissue is rare. To overcome this limitation and to study gene-metabolite covariation in cancer, we assemble the Cancer Atlas of Metabolic Profiles of metabolomic and transcriptomic data from 988 tumour and control specimens spanning 11 cancer types in published and newly generated datasets. Meta-analysis of the Cancer Atlas of Metabolic Profiles reveals two classes of gene-metabolite covariation that transcend cancer types. The first corresponds to gene-metabolite pairs engaged in direct enzyme-substrate interactions, identifying putative genes controlling metabolite pool sizes. A second class of gene-metabolite covariation represents a small number of hub metabolites, including quinolinate and nicotinamide adenine dinucleotide, which correlate to many genes specifically expressed in immune cell populations. These results provide evidence that gene-metabolite covariation in cellularly heterogeneous tissue arises, in part, from both mechanistic interactions between genes and metabolites, and from remodelling of the bulk metabolome in specific immune microenvironments.

publication date

  • June 19, 2023

Research

keywords

  • Metabolomics
  • Neoplasms

Identity

PubMed Central ID

  • PMC10290959

Scopus Document Identifier

  • 85162229514

Digital Object Identifier (DOI)

  • 10.1093/nar/gkaa1020

PubMed ID

  • 37337120

Additional Document Info

volume

  • 5

issue

  • 6