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. 2020 Mar 23;22(2):1751–1766. doi: 10.1093/bib/bbaa002

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© The Author(s) 2020. Published by Oxford University Press.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

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IN construction. The formation of INs and their overlap with CNs can reveal metabolic pathways that are regulated specifically in a tissue of interest. A, Formation of an IN through the integration of GEMs with other biological networks, including regulatory networks, PPINs and signalling networks. INs are necessary in order to cover the entire biological functions of cells and tissues in a holistic manner and should enable a better prediction of the cell phenotype. Arrows with barbed heads, activatory relationships; arrows with bars, inhibitory relationships; dotted lines, physical interactions; and arrows with filled heads, integration of data. B, Overlap of an IN with a CN can reveal tissue-specific functional and physical interactions, which can then be used to determine BPs that are uniquely regulated in a tissue of interest.