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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 1351 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.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse phase, Liquid Chromatography MS - positive - reverse phase

PROVIDER: MTBLS10118 | MetaboLights | 2024-10-25

REPOSITORIES: MetaboLights

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Project description:Purpose: To characterize the functional implication of autophagy in the wheat response to stress, the key genes contributing in mediated salt tolerance of wheat seedlings through 3-MA were identified in normal or salt stress conditions in the presence or absence of added 3-MA by the transcriptome profiles. Methods: Four days after NaCl and 3-MA treatment, the roots and the third leaves were collected respectively with every 10 of them being mixed as one biological replicate for each treatment. Every treatment had four biological replicates. The wheat root and leaves mRNA profiles were generated by deep sequencing, in triplicate, using Illumina GAIIx. The sequence reads that passed quality filters were analyzed at the transcript isoform level with two methods: Burrows–Wheeler Aligner (BWA) followed by ANOVA (ANOVA) and TopHat followed by Cufflinks. qRT–PCR validation was performed using TaqMan and SYBR Green assays. Results: The RNA-Seq data had high quality and reliable results were obtained from the transcriptome assembly. A high correlation between biological replicates was observed for all treatments, which indicated that the four biological replicates were reliable in this study. Based on the principal component analysis (PCA), a clear separation between the NaCl-treated group and controls could be observed. The Q30 percentage (sequences with sequencing error rate lower than 0.1%) was over 94%, and the average GC content of the RNA-seq reads was 55.46%. After removing the adaptor and low-quality sequence, each library received 68310810-83844286 clean reads. These clean reads were mapped to the reference genome with match ratios in the range of 93.6%-95.9%, and 120744 genes predicted from the genome were found to be expressed (with FPKM > 0), including 25180 annotated genes in wheat genome. 3-MA treatment shifted the transcriptome a salt-stressed wheat seedling. The up-regulated DEGs and DEMs were increased, and the down-regulated DEGs and DEMs were decreased in 3-MA-added plants under NaCl stress condition. The study may help us understand the mechanism for 3-MA mediated salt tolerance and provide a theoretical basis for autophagy regulated salt response in wheat seedlings. Conclusions: 3-MA treatment shifted the transcriptome a salt-stressed wheat seedling. The up-regulated DEGs and DEMs were increased, and the down-regulated DEGs and DEMs were decreased in 3-MA-added plants under NaCl stress condition. The study may help us understand the mechanism for 3-MA mediated salt tolerance and provide a theoretical basis for autophagy regulated salt response in wheat seedlings.

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

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