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

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 dat...

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Autores principales: Shichkova, Polina, Coggan, Jay S., Markram, Henry, Keller, Daniel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8631404/
https://www.ncbi.nlm.nih.gov/pubmed/34858137
http://dx.doi.org/10.3389/fnmol.2021.604559
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author Shichkova, Polina
Coggan, Jay S.
Markram, Henry
Keller, Daniel
author_facet Shichkova, Polina
Coggan, Jay S.
Markram, Henry
Keller, Daniel
author_sort Shichkova, Polina
collection PubMed
description 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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spelling pubmed-86314042021-12-01 A Standardized Brain Molecular Atlas: A Resource for Systems Modeling and Simulation Shichkova, Polina Coggan, Jay S. Markram, Henry Keller, Daniel Front Mol Neurosci 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. Frontiers Media S.A. 2021-11-10 /pmc/articles/PMC8631404/ /pubmed/34858137 http://dx.doi.org/10.3389/fnmol.2021.604559 Text en Copyright © 2021 Shichkova, Coggan, Markram and Keller. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Shichkova, Polina
Coggan, Jay S.
Markram, Henry
Keller, Daniel
A Standardized Brain Molecular Atlas: A Resource for Systems Modeling and Simulation
title A Standardized Brain Molecular Atlas: A Resource for Systems Modeling and Simulation
title_full A Standardized Brain Molecular Atlas: A Resource for Systems Modeling and Simulation
title_fullStr A Standardized Brain Molecular Atlas: A Resource for Systems Modeling and Simulation
title_full_unstemmed A Standardized Brain Molecular Atlas: A Resource for Systems Modeling and Simulation
title_short A Standardized Brain Molecular Atlas: A Resource for Systems Modeling and Simulation
title_sort standardized brain molecular atlas: a resource for systems modeling and simulation
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8631404/
https://www.ncbi.nlm.nih.gov/pubmed/34858137
http://dx.doi.org/10.3389/fnmol.2021.604559
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