Fig. 2

Comparison of gene expression between CM, NCM and MM shows endocannabinoid signalling in CM, neurodegenerative pathways with MM and drug resistance pathways were associated with NCM. Panels a, b and d show GO expression analysis results and e and f show pathway analysis results of the genes expressed exclusively in CM, NCM or MM in the Venn diagram in (c). 27 genes are expressed exclusively in CM while in the NCM there are 247 genes and in MM 352 genes exclusively expressed. Most genes (2876) are expressed in common in all disease states. a The GO analysis reveals signal transduction abnormality, neutrophil degranulation and negative regulation of gene expression amongst the most significantly expressed GO terms in the 27 CM genes. b Amongst the significant GO terms for the 247 genes expressed exclusively in NCM were microtubule organizing center organization, glutathione metabolic process, glutathione derivative biosynthetic process, oxidation–reduction process, DNA damage checkpoint, mitotic cell cycle arrest, reactive oxygen species biosynthetic process, removal of superoxide radicals, detoxification, activation of mitogen-activated protein kinases (MAP3Ks) activity, negative regulation of cytoskeleton organization and amyloid-beta clearance. These terms are suggestive of glutathione involvement in defense against ROS in severe malaria, DNA damage repair mechanisms, cytoskeletal destabilization activation and protein clearance. d Elevated GO terms for the 352 genes exclusively expressed in MM included biogenesis, regulation of nitrogen compound metabolic process, positive regulation of protein metabolic process, response to biotic stimulus, DNA damage response, detection of DNA damage, positive regulation of phospholipid metabolic process, blood vessel remodeling, cell cycle arrest, response to unfolded protein, immune response and interleukin (IL)-10 production, which are indicative of DNA repair mechanisms, cellular repair and anti-inflammatory mechanisms. e Over-represented KEGG pathways for the CM-exclusive genes included retrograde endocannabinoid signalling and f over-represented KEGG pathways for the MM-exclusive genes included non-small cell lung cancer, endometrial cancer, Epstein-Barr virus (EBV) infection, base excision repair and mismatch repair-which are pointers to DNA damage and increased risk of cancer development—and also pathways for Parkinson’s and prion disease thus reflecting distinct neurodegenerative gene expression patterns in MM