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. 2020 Dec 1;10:20970. doi: 10.1038/s41598-020-77847-9

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© The Author(s) 2020

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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/.

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An example of where Pascal pathway enrichment and HotNet2 home in on the same pathway causal of Hyperlipidaemia. The Hotnet2 module (black interactions) was detected using HCGHs (red) from a Hyperlipidaemia GWAS and the OmniPath network. This module is enriched for 3 successful drug targets (bold node border), one of which, PCSK9, was not categorised as a HCGH in the input. The Pascal enriched pathway (red interactions) is the lipoprotein metabolism pathway from Metabase. Genes that have a significant Pascal gene score are highlighted in yellow: it can also be seen that an additional novel drug target was recovered (MTTP) using this method that did not have any type of genetic evidence associated with it.