Comics take on: glycoprotein acetyls

posted in: Comics

Glycoprotein Acetyls (GlycA) is a read-out of the Nightingale (formerly Brainshake) platform. GlycA has been proposed as a novel inflammatory biomarker (see references below).

Let’s take a look at the network around this interesting biomarker.

Click here to access the GlycA network on comics

The first neighborhood of GlycA on comics

We find four associations with DNA methylation (CpG’s) on chromosomes 1 (MSTO1), 2 (MFSD6), 4 (MTERFD1; PTDSS1), and 14 (NPC2; ISCA2) … an interesting starting point for further research on why these four sites associate with GlycA.

Why am I saying this? Read our review “Connecting the epigenome, metabolome and proteome for a deeper understanding of disease” in the Journal of Internal Medicine. The idea is that methylation of certain CpG sites is a readout for the body’s response to physiological challenge. Here are the annotations of the genes that may be regulated by these four CpG’s. Three out of the four CpG’s appear to be involved in mitochondrial function:

  • MSTO1 (Misato Mitochondrial Distribution And Morphology Regulator 1) is involved in the regulation of mitochondrial distribution and morphology [ref].
  • MFSD6 (Major Facilitator Superfamily Domain Containing 6) is predicted to enable MHC class I protein binding activity and MHC class I receptor activity [ref].
  • PTDSS1 (Phosphatidylserine Synthase 1) catalyzes the formation of phosphatidylserine (PS). PS localizes to the mitochondria-associated membrane of the endoplasmic reticulum, where it serves a structural role as well as a signaling role [ref]; MTERFD1 (aka Mitochondrial Transcription Termination Factor 3 or MTERF3) is required for normal mitochondrial function [ref].
  • NPC2 (NPC Intracellular Cholesterol Transporter 2) may function in regulating the transport of cholesterol through the late endosomal/lysosomal system [ref]; ISCA2 (Iron-Sulfur Cluster Assembly 2) appears to be involved in the maturation of mitochondrial iron-sulfur proteins [ref].

The two mutual best hits to the proteomics platforms Olink (CFHR5) and Somalogic (SERPIND1) are major glycoproteins … another interesting starting point for further research into what their link is to GlycA.

Now expand the network to a larger neighborhood by setting the maximum number of nodes to 60 and enjoy the richness of glycosylation related multiomics … incl. lots of N-glycosylation traits (PGP platform), IgA glycans (IgA platform), HbA1c (clinical biochemistry), and mannose (Metabolon HD2 and HD4).

Again – much to discover, interpret and hypothesize here. Enjoy!

Tip: Click on the “Export” tab in comics to get all details for the nodes and edges in the presently displayed network.

Click here to access the GlycA network with a larger neighborhood

Tip: Read our paper “Fine-Mapping of the Human Blood Plasma N-Glycome onto Its Proteome” for an integration of the Somalogic and the total N-glycan data from QMDiab.

References on GlycA as an inflammatory marker

  • Associations between Adverse Childhood Experiences and the novel inflammatory marker glycoprotein acetyls in two generations of the Avon Longitudinal Study of Parents and Children birth cohort, Brain, Behavior, and Immunity, 2022
  • Glycoprotein Acetyls: A Novel Inflammatory Biomarker of Early Cardiovascular Risk in the Young, Journal of the American Heart Association, 2022
  • Biomarker Glycoprotein Acetyls Is Associated With the Risk of a Wide Spectrum of Incident Diseases and Stratifies Mortality Risk in Angiography Patients, Genomic and Precision Medicine, 2018
  • Circulating N-Linked Glycoprotein Acetyls and Longitudinal Mortality Risk, Circulation Research, 2016
  • Glycoprotein acetyls (GlycA) at 12 months are associated with high-sensitivity C-reactive protein and early life inflammatory immune measures, Pediatric Research, 2019
  • Association of N-Linked Glycoprotein Acetyls and Colorectal Cancer Incidence and Mortality, PLoS One, 2016