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. 2018 Jan 8;8:36. doi: 10.1038/s41598-017-18317-7

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© The Author(s) 2017

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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A metabolic network showing how trimester-related metabolic pathways are interconnected with common metabolites. The metabolic pathways are connected by Kamada-Kawai layout that relates the layout of metabolites to a dynamic spring system and minimizes metabolic reactions between metabolites within a metabolic network. The metabolites placed closer together will have stronger springs strength which are calculated by the inverse proportion to the square of the shortest graphical distance between two metabolites (the spring attraction was set to 68). The significantly altered metabolites throughout pregnancy are shown by the red circles and the non-significant metabolites by yellow circles. The red lines connect the significant metabolites. The topology of network is organized to have the most connected metabolites situated in the center of network.