Transcriptomics integrated with metabolomics reveals partial molecular mechanisms of nutritional risk and neurodevelopment in children with congenital heart disease.

ABSTRACT

Purpose: To explore molecular mechanisms affecting nutritional risk and neurodevelopment in children with congenital heart disease (CHD) by combining transcriptome and metabolome analysis. Methods: A total of 26 blood and serum samples from 3 groups of children with CHD low nutritional risk combined with normal neurodevelopment (group A), low nutritional risk combined with neurodevelopmental disorders (group B) and high nutritional risk combined with normal neurodevelopment (group C) were analyzed by transcriptome and metabolomics to search for differentially expressed genes (DEGs) and metabolites (DEMs). Functional analysis was conducted for DEGs and DEMs. Further, the joint pathway analysis and correlation analysis of DEGs and DEMs were performed. Results: A total of 362 and 1,351 DEGs were detected in group B and C compared to A, respectively. A total of 6 and 7 DEMs were detected in group B and C compared to A in positive mode, respectively. There were 39 and 31 DEMs in group B and C compared to A in negative mode. Transcriptomic analysis indicated that neurodevelopment may be regulated by some genes such as NSUN7, SLC6A8, CXCL1 and LCN8, nutritional risk may be regulated by SLC1A3 and LCN8. Metabolome analysis and joint pathway analysis showed that tryptophan metabolism, linoleic and metabolism and glycerophospholipid metabolism may be related to neurodevelopment, and glycerophospholipid metabolism pathway may be related to nutritional risk. Conclusion: By integrating transcriptome and metabolome analyses, this study revealed key genes and metabolites associated with nutritional risk and neurodevelopment in children with CHD, as well as significantly altered pathways. It has important clinical translational significance.