4.3 Results
4.3.5 Properties of MHC proteins with novel variants identified from the
In addition to common and clinical variants, the novel variants in the MHC region that were identified from the sequence graph created in chapter3were mapped to the host-pathogen PPIN. All variants identified were included regardless of the gene region, so that the
possibilities for exploring the impact of non-coding variants on the PPIs could be illustrated.
Table 4.9Novel MHC variants that were mapped to the PPIN
Variant type Number of variants Number of proteins
exonic 3 3
upstream 9 3
UTR3 10 1
downstream 16 5
intronic 53 12
intergenic 1199 27
Of the 1377 variants identified, 1290 (93.68%) mapped to proteins in the PPIN. There were only 3 exonic variants and 1199 (92.95%) intergenic variants of which 172 had both genes in the PPIN. The number of variants by location is displayed in Table4.9.
The 1290 variants mapped to 36 proteins, of which 30 were classified as MHC proteins. The six non-MHC proteins were included, because intergenic variants could also map to genes outside of the MHC region. Of the MHC proteins, ten interacted with HIV-1 proteins, ten interacted with bridge proteins and two interacted with drug targets. In addition, seven were differentially expressed during HIV-TB co-infection. A visualisation of the variants and
interactions is displayed in Figure4.3. In addition, a list of the 30 MHC proteins is provided in Table7.8with a summary of the number of variants, pathogen interactions, bridge protein interactions, drug target interactions, differential expression, and priority ranking.
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Zidovudine Saquinavir Isoniazid Rifampicin Figure4.3VisualisationofMHCproteins,withtheirvariantsandinteractions.ThevisualisationshowsMHCproteins(yellow),differentiallyexpressedproteins (orange)aswellastheirinteractionswithbridgeproteins(red),HIV-1proteins(green),Mtbproteins(blue),drugtargetproteins(lightpink),anddrugs(dark pink).ItalsoshowslinkstovariantsintheMHCproteins,withsmallergreycirclesrepresentingknownvariants,largergreycirclesrepresentingnovelvariants andbeigecirclesrepresentingknownvariantswithhigherallelefrequencyinanAfricanpopulation.Intergenicnovelvariantswereexcludedfromthevisualisation forclarity.Thelightgreycircleoverthesubnetworkonthetoprightisacontinuationofthelargesubnetworkontheleftwhereitgetscut-offatthebottom ofthepage.OntheleftthevisualisationshowsacomplexsubnetworkofinteractionsbetweenmanydifferentMHCproteins,bridgeproteinsandpathogen proteins.OntherightasimplesubnetworkisshownillustratingtheinteractionbetweenaMHCprotein(DDR1)andadrug-targetprotein(PTGS2)aswellas thedrug(Aminosalicylicacid).EightvariantsofDDR1aredisplayed,threeofwhicharenovelandfourhadahigherfrequencyinanAfricanpopulation.This subnetworkisavailableinaninteractivevieweratthefollowinglink:https://www.ndexbio.org/#/network/6ddf7917-7700-11ec-b3be-0ac135e8bacf?accesskey= af63b2847108576c058f7575e2f48b703877fe56c35d2f6336c601acc6ba5985.