ArticleCell metabolism2026
Digital twins for in vivo metabolic flux estimations in patients with brain cancer.
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Article in Cell metabolism, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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9citing papers in PubMed
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Who cites it
9 citing papers in PubMed.
- Microenvironment-derived acetylated amino acids promote glioblastoma treatment resistance.Research square · 2026Article
- Decoding the cancer microbiome: multi-omics, AI, and translational opportunities.Genome biology · 2026Review
- Accelerating discovery: Transformative clinical trial models in neuro-oncology.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- Cancer Heterogeneity and Cancer Cell Plasticity: Molecular Mechanisms and Precision Therapy.MedComm · 2026Review
- Digital Twins as the Implementation Layer of Precision Medicine in Pediatric Neurosurgery.Journal of Korean Neurosurgical Society · 2026Review
- Molecular Oncodiagnostics in Precision Oncology: Integrating Tumor Transcriptomics, Patient Pharmacogenetics, and Ex Vivo Chemoresistance Testing to Improve Individual Chemotherapy Response.Journal of personalized medicine · 2026Review
- Digital twins for in vivo metabolic flux estimations in patients with brain cancer.Cell metabolism · 2026Article
- Shaping the future of multiple myeloma with artificial intelligence and digital twins: from concept to clinic.Frontiers in digital health · 2026Review
- New directions for complex systems in contemporary neuroscience: a morphodynamic and emergent function approach.Frontiers in computational neuroscience · 2026Review
Corrections and comments
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Authors and funding
21 authors.
Baharan MeghdadiDepartment of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA; Laboratory for Systems Biology of Human Diseases, University of Michigan, Ann Arbor, MI, USA.
Wajd N Al-HolouRogel Cancer Center, University of Michigan, Ann Arbor, MI, USA; Department of Neurosurgery, University of Michigan, Ann Arbor, MI, USA.
Andrew J ScottRogel Cancer Center, University of Michigan, Ann Arbor, MI, USA; Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
Anjali MittalDepartment of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA; Laboratory for Systems Biology of Human Diseases, University of Michigan, Ann Arbor, MI, USA.
Ningning LiangDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
Palavalasa SravyaDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
Abhinav AchrejaBiointerfaces Institute, University of Michigan, Ann Arbor, MI, USA; Laboratory for Systems Biology of Human Diseases, University of Michigan, Ann Arbor, MI, USA; Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.
Alexandra O'BrienDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
Kathy DoDepartment of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA; Laboratory for Systems Biology of Human Diseases, University of Michigan, Ann Arbor, MI, USA.
Zhe WuDepartment of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
Jiane FengDepartment of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
Nathan R QiDepartment of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
Vijay TarnalDepartment of Anesthesiology, University of Michigan, Ann Arbor, MI, USA.
Sriram VennetiDepartment of Pathology, University of Michigan, Ann Arbor, MI, USA.
C Ryan MillerDepartment of Pathology, University of Alabama Birmingham, Birmingham, AL, USA.
Jann N SarkariaDepartment of Radiation Oncology, Mayo Clinic, Rochester, MN, USA.
Weihua ZhouRogel Cancer Center, University of Michigan, Ann Arbor, MI, USA; Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
Theodore S LawrenceRogel Cancer Center, University of Michigan, Ann Arbor, MI, USA; Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
Costas A LyssiotisRogel Cancer Center, University of Michigan, Ann Arbor, MI, USA; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA; Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, MI, USA. Electronic address: clyssiot@umich.edu.
Daniel R WahlRogel Cancer Center, University of Michigan, Ann Arbor, MI, USA; Department of Neurosurgery, University of Michigan, Ann Arbor, MI, USA; Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA. Electronic address: dwahl@med.umich.edu.
Deepak NagrathDepartment of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA; Laboratory for Systems Biology of Human Diseases, University of Michigan, Ann Arbor, MI, USA; Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA. Electronic address: dnagrath@umich.edu.
Funding
Translational Pathology CoreP50CA269022 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Mats Ljungman · 2023 to 2026
$10.0MMetabolic Phenotyping in Live Models of Obesity and DiabetesU2CDK135066 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Carol Fuzeti Elias · 2023 to 2026
$3.5MTargeting Nucleotide Metabolism to Overcome Therapy Resistance in GlioblastomaR37CA258346 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Daniel R Wahl · 2021 to 2026
$3.3MTargeting integrated metabolic and epigenetic pathways in childhood ependymomasR01CA261926 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Deepak Nagrath, Benita Tamrazi · 2022 to 2026
$3.0MTargeting Stromal Influences on BCKA Addiction in PDAC TumorsR01CA271369 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI THEODORE S LAWRENCE, Deepak Nagrath · 2022 to 2026
$2.8MNew methods to measure and interrupt metabolic fluxes in brain cancerR01CA298159 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI NAGRATH, DEEPAK, WAHL, DANIEL R · 2025 to 2025
$2.8MUnravelling metabolic dependencies in H3K27M mutant DIPGR01NS110572 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Sriram Venneti · 2019 to 2026
$2.7MInhibition of wild-type IDH1 as a ferroptosis-inducing therapeutic approach for the treatment of malignant glioma.R01NS129123 · NINDS · WASHINGTON UNIVERSITY · PI Alexander H. Stegh, Daniel R Wahl · 2022 to 2026
$2.4MTargeting metabolic dependencies in ZFTA-RELA fusion childhood ependymomasR01NS127799 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Sriram Venneti · 2023 to 2026
$1.8MDe Novo Nucleotide Synthesis as a Mediator of Radiation Resistance and a Therapeutic Target in GlioblastomaK08CA234416 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WAHL, DANIEL R · 2019 to 2023
$1.1MDefining Tumor Microenvironmental Interactions that drive THY1-Mediated Treatment Resistance in GlioblastomaK08NS128271 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Wajd Al-Holou · 2024 to 2026
$700kDefining and interrupting metabolic crosstalk in the glioblastoma microenvironmentK99CA300923 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Andrew Joseph Scott · 2025 to 2026
$273kNCI NIH HHS F32 CA260735NCI NIH HHS K08 CA234416NCI NIH HHS K99 CA300923NCI NIH HHS P50 CA269022NCI NIH HHS R01 CA261926NCI NIH HHS R01 CA271369NCI NIH HHS R01 CA298159NCI NIH HHS R37 CA258346NIDDK NIH HHS U2C DK135066NINDS NIH HHS K08 NS128271NINDS NIH HHS R01 NS110572NINDS NIH HHS R01 NS127799NINDS NIH HHS R01 NS129123
Abstract
Recent advancements in metabolic flux estimations in vivo are limited to preclinical models, primarily due to challenges in tissue sampling, tumor microenvironment (TME) heterogeneity, and non-steady-state conditions. To address these limitations and enable flux estimation in human patients, we developed two machine learning-based frameworks. First, the digital twin framework (DTF) integrates first-principles stoichiometric and isotopic simulations with convolutional neural networks to estimate fluxes in patient bulk samples. Second, the single-cell metabolic flux analysis (
Indexed as
Brain NeoplasmsGliomaMetabolic Flux AnalysisAnimalsHumansMachine LearningMiceSingle-Cell AnalysisTumor Microenvironment(13)C-single-cell metabolic flux analysiscancer metabolismglioblastomain vivo isotope tracingin vivo metabolismmachine learningpurine metabolismscRNA-seqserine metabolismtumor microenvironment
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.