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research article

A Standardized Brain Molecular Atlas: A Resource for Systems Modeling and Simulation

Shichkova, Polina  
•
Coggan, Jay S.  
•
Markram, Henry  
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November 10, 2021
Frontiers In Molecular Neuroscience

Accurate molecular concentrations are essential for reliable analyses of biochemical networks and the creation of predictive models for molecular and systems biology, yet protein and metabolite concentrations used in such models are often poorly constrained or irreproducible. Challenges of using data from different sources include conflicts in nomenclature and units, as well as discrepancies in experimental procedures, data processing and implementation of the model. To obtain a consistent estimate of protein and metabolite levels, we integrated and normalized data from a large variety of sources to calculate Adjusted Molecular Concentrations. We found a high degree of reproducibility and consistency of many molecular species across brain regions and cell types, consistent with tight homeostatic regulation. We demonstrated the value of this normalization with differential protein expression analyses related to neurodegenerative diseases, brain regions and cell types. We also used the results in proof-of-concept simulations of brain energy metabolism. The standardized Brain Molecular Atlas overcomes the obstacles of missing or inconsistent data to support systems biology research and is provided as a resource for biomolecular modeling.

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Type
research article
DOI
10.3389/fnmol.2021.604559
Web of Science ID

WOS:000733724500001

Author(s)
Shichkova, Polina  
Coggan, Jay S.  
Markram, Henry  
Keller, Daniel  
Date Issued

2021-11-10

Publisher

FRONTIERS MEDIA SA

Published in
Frontiers In Molecular Neuroscience
Volume

14

Article Number

604559

Subjects

Neurosciences

•

Neurosciences & Neurology

•

molecular concentrations

•

neuroproteomics

•

quantitative resource

•

data integration

•

mouse brain

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systems modelling and simulation

•

differential protein expression

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meta-analysis

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flux-balance analysis

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thermodynamically infeasible loops

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pentose-phosphate pathway

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human metabolome database

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mass-spectrometry

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energy-metabolism

•

rat-brain

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liquid-chromatography

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mouse-brain

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glycogen-synthase

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
BBP-CORE  
Available on Infoscience
January 15, 2022
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/184468
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