Synthetic messenger RNA vaccines and transcriptomic dysregulation: Evidence from new-onset adverse events and cancers post-vaccination

Table 2 Gene set enrichment results for group 1 categorized by molecular pathway

Molecular pathways	MSigDB standard name	Normalized Enrichment Score	False discovery rate
Mitochondrial electron transport dysfunction and reactive oxygen species	KEGG_MEDICUS_REFERENCE_MITOCHONDRIAL_COMPLEX_UCP1_IN_THERMOGENESIS	1.86	0.11
	KEGG_MEDICUS_REFERENCE_ELECTRON_TRANSFER_IN_COMPLEX_I	1.70	0.10
	KEGG_MEDICUS_VARIANT_MUTATION_INACTIVATED_PINK1_TO_ELECTRON_TRANSFER_IN_COMPLEX_I	1.73	0.09
	KEGG_MEDICUS_VARIANT_MUTATION_CAUSED_ABERRANT_ABETA_TO_ELECTRON_TRANSFER_IN_COMPLEX_I	1.69	0.09
	KEGG_MEDICUS_VARIANT_MUTATION_CAUSED_ABERRANT_SNCA_TO_ELECTRON_TRANSFER_IN_COMPLEX_I	1.66	0.11
	HALLMARK_OXIDATIVE_PHOSPHORYLATION	1.43	> 0.001
Proteasome-mediated protein degradation stress	KEGG_MEDICUS_VARIANT_MUTATION_CAUSED_ABERRANT_ABETA_TO_26S_PROTEASOME_MEDIATED_PROTEIN_DEGRADATION	1.78	0.12
	KEGG_MEDICUS_VARIANT_MUTATION_INACTIVATED_VCP_TO_26S_PROTEASOME_MEDIATED_PROTEIN_DEGRADATION	1.74	0.13
	KEGG_MEDICUS_VARIANT_MUTATION_CAUSED_ABERRANT_SOD1_TO_26S_PROTEASOME_MEDIATED_PROTEIN_DEGRADATION	1.73	0.09
	GOBP_PROTEIN_CONTAINING_COMPLEX_REMODELING	-2.11	> 0.001
Transcriptomic instability and translational stress	REACTOME_EUKARYOTIC_TRANSLATION_INITIATION	3.11	> 0.001
	REACTOME_SRP_DEPENDENT_COTRANSLATIONAL_PROTEIN_TARGETING_TO_MEMBRANE	3.08	> 0.001
	REACTOME_NONSENSE_MEDIATED_DECAY_NMD	2.9	> 0.001
	KEGG_MEDICUS_REFERENCE_TRANSLATION_INITIATION	3.0	> 0.001
	GOBP_CYTOPLASMIC_TRANSLATION	2.60	> 0.001
	GOBP_RIBOSOMAL_SMALL_SUBUNIT_BIOGENESIS	2.35	> 0.001
	GOBP_RIBOSOMAL_LARGE_SUBUNIT_BIOGENESIS	2.34	> 0.001
Systemic inflammatory and immune response	GSE22886_NAIVE_TCELL_VS_DC_UP	2.43	> 0.001
	GSE2405_0H_VS_9H_A_PHAGOCYTOPHILUM_STIM_NEUTROPHILS_UP	2.36	> 0.001
	GSE7400_CTRL_VS_CSF3_IN_VIVO_TREATED_PBMC_UP	2.27	> 0.001
	GSE7400_CTRL_VS_CSF3_IN_VIVO_TREATED_PBMC_DN	-1.93	> 0.001
	GSE6269_E_COLI_VS_STREP_PNEUMO_INF_PBMC_DN	-1.9	> 0.001
	GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE	-1.95	> 0.001
	GOBP_HUMORAL_IMMUNE_RESPONSE	-1.91	0.006
Endothelium dysfunction	HALLMARK_ANGIOGENESIS	-1.94	> 0.001
Proliferative signaling and suppressed tumor control	HALLMARK_MYC_TARGETS_V1	1.64	> 0.001
	GAVISH_3CA_MALIGNANT_METAPROGRAM_3_CELL_CYLCE_HMG_RICH	1.77	0.005
	HALLMARK_KRAS_SIGNALING_DN	-1.68	> 0.001
	HALLMARK_P53_PATHWAY	-1.50	0.038
	KEGG_MEDICUS_REFERENCE_WNT_SIGNALING_MODULATION_WNT_INHIBITOR	-1.56	0.89

The Table 2 displays the top gene sets within each category, along with their corresponding MSigDB identifiers, Normalized Enrichment Score (NES), and false discovery rate (FDR) q value. Positive NES values indicate upregulation, while negative NES values indicate downregulation of the gene sets in vaccinated samples (group 1) relative to controls. Gene sets were selected based on biological relevance and NES >|15| with FDR q < 0.25. Group 1 includes patients with new-onset adverse events following messenger RNA coronavirus disease 2019 vaccination (n = 3), compared with normal controls (n = 803 unvaccinated individuals from the GTEx dataset).