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Related Concept Videos

Metabolic Rate01:25

Metabolic Rate

The human body is a powerhouse of energy, with every cell performing numerous functions that require energy. This energy production and consumption is measured by the metabolic rate, which quantifies the total heat generated by all the body's chemical reactions and mechanical work. This measurement helps to determine the rate of kilocalorie (kcal) consumption needed to fuel all ongoing activities.
The Basal Metabolic Rate (BMR) measures the energy expended at rest.
Several factors influence the...

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Reference-guided computational framework identifies microenvironment metabolic subtypes and targets using pan-cancer

Ke Tang1,2,3, Ya Han1,2,3, Dongqing Sun1,2,3

  • 1Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Department of Orthopedics, School of Life Science and Technology, Tongji Hospital, Tongji University, Shanghai, 200092, China.

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|December 20, 2025
PubMed
Summary

We developed MetroSCREEN, a computational tool to map cancer cell metabolism and identify key regulators. This approach reveals novel targets for cancer therapies by analyzing metabolic heterogeneity at single-cell resolution.

Keywords:
Immunotherapy responseLarge-scale data integrationMetabolic regulationSingle-cell transcriptomicsTumor microenvironment

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Area of Science:

  • Computational biology
  • Cancer research
  • Metabolomics

Background:

  • Metabolic reprogramming is a key cancer hallmark, but its heterogeneity in the tumor microenvironment is poorly understood.
  • Existing methods lack reaction-level insights and upstream regulator identification, limiting clinical translation.

Purpose of the Study:

  • To develop a computational framework, MetroSCREEN, for inferring reaction-level metabolic flux and identifying upstream regulators from transcriptomic data.
  • To characterize metabolic heterogeneity and discover novel therapeutic targets in cancer.

Main Methods:

  • MetroSCREEN employs an enrichment-based procedure for reaction-level metabolic activity quantification.
  • It integrates gene-regulatory signals and cell-cell interactions to define metabolic regulons.
  • A causal discovery module infers regulatory directionality for robust regulator nomination.

Main Results:

  • MetroSCREEN accurately predicts reaction-level metabolic activities and regulators using transcriptomic-metabolomic data and single-cell CRISPR screens.
  • Analysis of a pan-cancer atlas revealed ZNF281/STAT1 regulate collagen metabolism and APOE/KLF7 regulate sphingolipid metabolism and antigen presentation.
  • Identified metabolic subtypes and regulators linked to patient survival and immunotherapy response.

Conclusions:

  • MetroSCREEN offers a robust, scalable method for dissecting metabolic heterogeneity at single-cell resolution.
  • It pinpoints metabolic regulators, uncovering potential antitumor targets for metabolic interventions.