Integrative analysis unveils the correlation of aminoacyl-tRNA biosynthesis metabolites with the methylation of the SEPSECS gene in Huntington’s disease brain tissue

Sangeetha Vishweswaraiah, Ali Yilmaz, Nazia Saiyed, Abdullah Khalid, Purvesh R. Koladiya, Xiaobei Pan, Shirin Macias, Andrew C. Robinson, David Mann, Brian D. Green, Ieva Kerševičiūte, Juozas Gordevičius, Uppala Radhakrishna, Stewart F. Graham*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)
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Abstract

The impact of environmental factors on epigenetic changes is well established, and cellular function is determined not only by the genome but also by interacting partners such as metabolites. Given the significant impact of metabolism on disease progression, exploring the interaction between the metabolome and epigenome may offer new insights into Huntington’s disease (HD) diagnosis and treatment. Using fourteen post-mortem HD cases and fourteen control subjects, we performed metabolomic profiling of human postmortem brain tissue (striatum and frontal lobe), and we performed DNA methylome profiling using the same frontal lobe tissue. Along with finding several perturbed metabolites and differentially methylated loci, Aminoacyl-tRNA biosynthesis (adj p-value = 0.0098) was the most significantly perturbed metabolic pathway with which two CpGs of the SEPSECS gene were correlated. This study improves our understanding of molecular biomarker connections and, importantly, increases our knowledge of metabolic alterations driving HD progression.

Original languageEnglish
Article number1752
Number of pages14
JournalGenes
Volume14
Issue number9
DOIs
Publication statusPublished - 02 Sept 2023

Keywords

  • Brain
  • Metabolomics
  • Epigenetics
  • Huntington’s Disease
  • Integrative Omics
  • Epi-Metabolomics
  • Humans
  • Huntington Disease
  • Amino Acyl-tRNA Synthetases
  • RNA, Transfer
  • Methylation
  • Metabolome

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