Multi-Omics Biomarkers in 22q11.2 Deletion Syndrome

Psychiatric and developmental conditions in 22q11.2 deletion syndrome (22q11.2DS) are common, yet clinicians have had no reliable blood test to flag who is at risk or to track disease over time. In a study our Dalton Bioanalytics scientists co-authored with the UC Davis MIND Institute, we asked a direct question: can untargeted metabolomics and proteomics read coordinated molecular changes in plasma that single-layer tests miss? Profiling proteins and metabolites together turned out to reveal a signature neither layer showed alone.

What we measured

We ran untargeted metabolomic and proteomic profiling on plasma from 30 participants in a longitudinal cohort: 16 individuals with 22q11.2DS and 14 typically developing controls. Because samples were collected over time, the design let us look not just at a single snapshot but at how the molecular profile tracked with clinical course. The goal was a plasma signature that informs the biological mechanisms behind the syndrome's neurodevelopmental and psychiatric features.

Key findings

• Lower taurine and arachidonic acid: both metabolites were significantly reduced in the 22q11.2DS group, pointing to altered lipid and amino-acid metabolism.

• Sixteen differentially expressed proteins (adjusted P < 0.05) spanning roughly 70 pathways, including gene expression, PI3K-Akt signaling, and the complement system.

• Complement and coagulation cascade shifts: C3, C4B, SERPINA1, and SERPING1 changed in expression. These components are increasingly tied to synapse pruning and the development of psychiatric symptoms.

• To our knowledge, this is the first plasma metabolic-plus-proteomic biomarker profile reported for 22q11.2DS.

Why measuring both layers mattered

The metabolite changes (taurine, arachidonic acid) and the protein changes (complement cascade) are not two separate stories. They converge on the same inflammatory and lipid-signaling biology, and that convergence is only visible when the metabolome and proteome are read on the same samples. This is the core of how we approach multi-omics biomarker discovery at Dalton: measuring proteins, metabolites, and lipids from one sample so coordinated, pathway-level signals are preserved rather than lost across separate platforms and batches. For the bigger picture, see our guide to multi-omics biomarker discovery methods and applications.

What it means

The identified metabolites and proteins are candidate biomarkers for the onset of comorbid conditions in 22q11.2DS, and the altered pathways offer testable mechanisms behind the neurodevelopmental phenotype. Just as important for translational work, a validated plasma signature could serve as a molecular outcome measure in future clinical trials, giving a way to assess early diagnosis and response to targeted treatment.

Citation

Zafarullah, M., Angkustsiri, K., Quach, A., Yeo, S., Durbin-Johnson, B. P., Bowling, H., & Tassone, F. (2024). Untargeted metabolomic and proteomic analysis identifies metabolic biomarkers and pathway alterations in individuals with 22q11.2 deletion syndrome. Metabolomics, 20(2), 31. https://doi.org/10.1007/s11306-024-02088-0. See more of our work on the Dalton Bioanalytics publications page.

Note

This article summarizes peer-reviewed research co-authored by Dalton Bioanalytics scientists. For full methods and results, please refer to the original publication.

By Seungjun Yeo, CEO at Dalton Bioanalytics. Specializing in multi-omics mass spectrometry for drug discovery and biomarker research.