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A multimodal atlas of tumour metabolism reveals the architecture of gene–metabolite covariation

E. Benedetti,E. Liu,Cerise Tang,F. Kuo,Mustafa Buyukozkan,Tricia Park,Jinsung Park,Fabian M. Correa,A. Hakimi,A. Intlekofer,J. Krumsiek,Ed Reznik

Published 2023 in Nature Metabolism

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. Benedetti et al. produce a Cancer Atlas of Metabolic Profiles from 988 metabolomic and transcriptomic tissue profiles across 15 studies to analyse and identify gene–metabolite interactions that transcend cancer types.

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