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Why has metabolomics been harder to standardize than DNA sequencing?

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Diagram illustrating metabolism with two sections: anabolic reaction on the left shows energy used to build larger molecules from smaller ones, while catabolic reaction on the right shows larger molecules breaking down into smaller molecules with energy released. — Metabolomics In anabolic reactions, a cell uses energy to combine small molecules into larger molecules. In catabolic reactions, molecules are broken down, and energy is released.

Standardizing metabolomics is significantly more complex than standardizing DNA sequencing due to the inherent chemical diversity of the metabolome, which far exceeds that of the genome, transcriptome, or proteome.1

The primary challenges include:

Extraction Variability: Unlike the relatively uniform nature of DNA, metabolites vary widely in their chemical properties. A single extraction protocol cannot efficiently recover both highly hydrophilic substances (such as lactic acid) and oily molecules (such as squalene) simultaneously.1
Instrumental Sensitivity: Metabolomics relies on nuclear magnetic resonance (NMR) and mass spectrometry. MS techniques often require extensive sample preparation, and interactions between biological samples and instrument surfaces can cause performance to fluctuate between runs.1
Lack of Universal Protocols: While genomics benefits from widely accepted standards and off-the-shelf technologies, metabolomics remains a specialized field where researchers must often devise their own unique assays and utilize expensive, highly specific instrumentation.1

Consequently, the field lacks the standardized, automated workflows that have become routine in genomics.1