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Table 3 Of the 40 top-ranked key drivers from the core oligodendrocyte-enriched Bayesian network (COLBN), 4 have a type of perturbation signature that we used to validate the network, either in vitro or in vivo

From: Multiscale network modeling of oligodendrocytes reveals molecular components of myelin dysregulation in Alzheimer’s disease

Gene Symbol

Major Annotated Roles of Gene Product

Myelin

OL Exosome

Lipid-Binding

AD Risk

Perturbation

ERMN

Myelination

Yes

    

UGT8

Galactocerebroside production

  

Yes

 

In vivo; this study

CNP

Myelination; Axon interaction

Yes

Yes

  

In vivo; this study

ENPP2

LPA production

     

FRMD4B

?

    

PLEKHH1

?

    

SLC44A1

Choline transporter

Yes

   

TRIM59

?

    

PLLP

Myelination

Yes

 

Yes

 

PRRG1

?

    

SOX2-OT

lncRNA

    

CONTIG36931_RC

?

    

CLDND1

?

    

ANLN

Actin cytoskeleton

Yes

   

TTYH2

Chloride channel

    

MYRF

OL differentiation

    

In vitro; [49]

FA2H

Ceramide hydroxylation

  

Yes

  

CARNS1

Carnosine production

    

RNLS

Alpha-NAD(P)H oxidase

    

RASSF2

Apoptosis

    

PRR18

?

    

RTKN

Rho pathway

    

DOCK10

Rho pathway

    

LPAR1

LPA receptor

Yes

 

Yes

 

MAG

Myelination

Yes

   

TF

Iron transport

    

TMEM125

?

    

PLP1

Myelination; Axon interaction

Yes

Yes

Yes

 

In vivo; this study

RHBDL2

Protease activity

     

NKX6–2

OL differentiation

    

FOLH1

Folate hydrolase

Yes

   

PSEN1

Protease activity

   

Yes

MAN2A1

Glycosylation

    

PLA2G16

Phospholipase

  

Yes

 

CONTIG56276_RC

?

    

ABCA2

Sterol transport

   

Yes

CREB5

?

   

Yes

GPR62

?

    

SLC31A2

Copper transport

    

LAMP2

Glycosylation

    
  1. The Major Annotated Roles of Gene Product column is based on a literature review for the major known role(s) of that gene’s product in oligodendrocytes, for which a question mark indicates that no major role is known, to the best of our knowledge. The Myelin column indicates whether or not that gene encodes a protein found in in the myelin proteome [43], the OL Exosome column indicates whether or not that gene encodes a protein found in the OL exosome proteome [97], and the lipid-binding column indicates whether or not that gene encodes a protein found in the set of lipid-binding proteins [98]. The AD risk indicates whether a variant associated with the gene has been previously associated with AD risk, and the Perturbation column indicates whether there is a perturbation signature that we used to corroborate the downstream neighborhood topology for that key driver
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Molecular Neurodegeneration

ISSN: 1750-1326