Generation and analysis of context-specific genome-scale metabolic models derived from single-cell RNA-Seq data
Artikel i vetenskaplig tidskrift, 2023

Single-cell RNA sequencing combined with genome-scale metabolic models (GEMs) has the potential to unravel the differences in metabolism across both cell types and cell states but requires new computational methods. Here, we present a method for generating cell-type-specific genome-scale models from clusters of single-cell RNA-Seq profiles. Specifically, we developed a method to estimate the minimum number of cells required to pool to obtain stable models, a bootstrapping strategy for estimating statistical inference, and a faster version of the task-driven integrative network inference for tissues algorithm for generating context-specific GEMs. In addition, we evaluated the effect of different RNA-Seq normalization methods on model topology and differences in models generated from single-cell and bulk RNA-Seq data. We applied our methods on data from mouse cortex neurons and cells from the tumor microenvironment of lung cancer and in both cases found that almost every cell subtype had a unique metabolic profile. In addition, our approach was able to detect cancer-associated metabolic differences between cancer cells and healthy cells, showcasing its utility. We also contextualized models from 202 single-cell clusters across 19 human organs using data from Human Protein Atlas and made these available in the web portal Metabolic Atlas, thereby providing a valuable resource to the scientific community. With the ever-increasing availability of single-cell RNA-Seq datasets and continuously improved GEMs, their combination holds promise to become an important approach in the study of human metabolism.






Johan Gustafsson

Chalmers, Biologi och bioteknik

Wallenberg Center for Protein Research (WCPR)

Petre Mihail Anton

Chalmers, Life sciences, Systembiologi

Fariba Roshanzamir

Chalmers, Life sciences, Systembiologi

Rebecka Jörnsten

Chalmers, Matematiska vetenskaper, Tillämpad matematik och statistik

Eduard Kerkhoven

Chalmers, Life sciences, Systembiologi

Jonathan Robinson

Chalmers, Life sciences, Systembiologi

BioInnovation Institute

Jens B Nielsen

Wallenberg Center for Protein Research (WCPR)

BioInnovation Institute

Chalmers, Life sciences, Systembiologi

Proceedings of the National Academy of Sciences of the United States of America

0027-8424 (ISSN) 1091-6490 (eISSN)

Vol. 120 6



Bioinformatik (beräkningsbiologi)

Bioinformatik och systembiologi





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