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<p>Generating condition-specific metabolic models by mapping gene expression data to genome-scale metabolic models (GEMs) is a routine approach to elucidate disease mechanisms from a metabolic perspective. On the other hand, integrating variants that perturb enzyme functionality from the same RNA-seq data may enhance GEM accuracy, offering insights into genome-wide metabolic pathology. Our study pioneers the extraction of both transcriptomic and genomic data from the same RNA-seq data to reconstruct personalized metabolic models. We map genes with significantly higher load of pathogenic variants in Alzheimer’s disease (AD) onto a human GEM together with the gene expression data. Comparative analysis of the resulting personalized patient metabolic models with the control models shows enhanced accuracy in detecting AD-associated metabolic pathways compared to the case where only expression data is mapped on the GEM. Besides, several otherwise would-be missed pathways are annotated in AD by considering the effect of genomic variants.</p>

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A personalized metabolic modelling approach through integrated analysis of RNA-Seq-based genomic variants and gene expression levels in Alzheimer’s disease

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年3月27日

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  • Dilara Uzuner Odongo,
  • Atılay İlgün,
  • Fatma Betül Bozkurt,
  • Tunahan Çakır

摘要

Generating condition-specific metabolic models by mapping gene expression data to genome-scale metabolic models (GEMs) is a routine approach to elucidate disease mechanisms from a metabolic perspective. On the other hand, integrating variants that perturb enzyme functionality from the same RNA-seq data may enhance GEM accuracy, offering insights into genome-wide metabolic pathology. Our study pioneers the extraction of both transcriptomic and genomic data from the same RNA-seq data to reconstruct personalized metabolic models. We map genes with significantly higher load of pathogenic variants in Alzheimer’s disease (AD) onto a human GEM together with the gene expression data. Comparative analysis of the resulting personalized patient metabolic models with the control models shows enhanced accuracy in detecting AD-associated metabolic pathways compared to the case where only expression data is mapped on the GEM. Besides, several otherwise would-be missed pathways are annotated in AD by considering the effect of genomic variants.