PT  - JOURNAL ARTICLE
AU  - Songjie Chen
AU  - Guangwen Wang
AU  - Xiaotao Shen
AU  - Daniel Hornburg
AU  - Shannon Rego
AU  - Rene Hoffman
AU  - Stephanie Nevins
AU  - Xun Cheng
AU  - Michael Snyder
TI  - Integration and comparison of multi-omics profiles of NGLY1 deficiency plasma and cellular models to identify clinically relevant molecular phenotypes
AID  - 10.1101/2021.05.28.446235
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.05.28.446235
4099  - http://biorxiv.org/content/early/2021/08/18/2021.05.28.446235.short
4100  - http://biorxiv.org/content/early/2021/08/18/2021.05.28.446235.full
AB  - NGLY1 (N-glycanase 1) deficiency is a rare congenital recessive disorder of protein deglycosylation unaddressed by the current standard of care. Using combined metabolomics and proteomics profiling, we show that NGLY1 deficiency activates the immune response and disturbs lipid metabolism, biogenic amine synthesis, and glutathione metabolism. These alterations were also observed in NGLY1 deficient patient-derived induced pluripotent stem cells (iPSCs) and differentiated neural progenitor cells (NPCs), which serve as personalized cellular models of the disease. These findings provide molecular insight into the pathophysiology of NGLY1 deficiency and suggest potential therapeutic strategies.Competing Interest StatementThe authors have declared no competing interest.