biostudies-literatureAlShaikhahmed KUS National Institutes of HealthNIAID NIH HHSPeter Stockley, University of LeedsEPSRCWellcome TrustBiotechnology and Biological Sciences Research CouncilEngineering and Physical Sciences Research Council12087-12098https://www.ebi.ac.uk/biostudies/studies/S-EPMC6294558biostudies-literatureUnknown46(22)Viruses with segmented genomes, including pathogens such as influenza virus, Rotavirus and Bluetongue virus (BTV), face the collective challenge of packaging their genetic material in terms of the correct number and types of segments. Here we develop a novel network approach to predict RNA-RNA interactions between different genomic segments. Experimental data on RNA complex formation in the multi-segmented BTV genome are used to establish proof-of-concept of this technique. In particular, we show that trans interactions between segments occur at multiple specific sites, termed segment assortment signals (SASs) that are dispersed across each segment. In order to validate the putative trans acting networks, we used various biochemical and molecular techniques which confirmed predictions of tNucleic acids researchDynamic network approach for the modelling of genomic sub-complexes in multi-segmented viruses.PMC6294558100218110145/Z/15/ZR01 AI045000BB/P00542X/1110145BB/P00542X110146BB/J014877/1EP/R023204/1R01AI045000Bingham RJAlShaikhahmed KSung PYTwarock RRoy PLeonov GfalseDynamic network approach for the modelling of genomic sub-complexes in multi-segmented viruses.Viruses with segmented genomes, including pathogens such as influenza virus, Rotavirus and Bluetongue virus (BTV), face the collective challenge of packaging their genetic material in terms of the correct number and types of segments. Here we develop a novel network approach to predict RNA-RNA interactions between different genomic segments. Experimental data on RNA complex formation in the multi-segmented BTV genome are used to establish proof-of-concept of this technique. In particular, we show that trans interactions between segments occur at multiple specific sites, termed segment assortment signals (SASs) that are dispersed across each segment. In order to validate the putative trans acting networks, we used various biochemical and molecular techniques which confirmed predictions of t2018-01-01T00:00:00Z2018 Dec2026-07-09T12:08:51.748Z2019-03-27T00:13:15ZS-EPMC62945583029949510.1093/nar/gky881