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Table 1 The 25 proteins selected for assay development

From: Development of robust targeted proteomics assays for cerebrospinal fluid biomarkers in multiple sclerosis

Accession

Name

Network*

CSF-PR score**

Datasets***

Selected keywords from UniProt and Gene Ontology

P51693

Amyloid-like protein 1

Yes

− 50

1 ↑ [56]

1 – [57]

4 ↓ [4, 5, 56]

Postsynaptic function, neurite outgrowth, neuronal apoptosis

P61769

Beta-2-microglobulin

Yes

60

3 ↑ [4, 5]

2 – [25, 57]

Component of the class I MHC, antigen presentation, innate immune response

P55290

Cadherin-13

Yes

− 75

3 ↓ [4, 5]

1 – [25]

Cell adhesion, negative regulator of neural cell growth

P16070

CD44 antigen

Yes

75

3 ↑ [4, 5]

1 – [25]

Mediates cell–cell and cell–matrix interactions, cell migration

P36222

Chitinase-3-like protein 1

 

70

8 ↑ [4, 5, 24, 25, 56]

1 – [22]

1 ↓ [56]

Lectin that binds glycans, no chitinase activity, inflammatory response, macrophage differentiation

Q15782

Chitinase-3-like protein 2

 

100

6 ↑ [4, 5, 25]

Lectin that binds glycans, no chitinase activity, carbohydrate metabolic process

P10645

Chromogranin-A

 

− 50

4 ↓ [4, 5, 22]

4 – [2, 25, 57]

Innate immune response, defence response (fungus, bacterium), negative regulation of neuron death

P12111

Collagen alpha-3(VI) chain

Yes

50

2 ↑ [4, 5]

2 – [4, 25]

Cell binding/adhesion, extracellular matrix organization

P02747

Complement C1q subcomponent subunit C

Yes

100

3 ↑ [4, 5]

Complement system, immune response

P00736

Complement C1r subcomponent

Yes

75

3 ↑ [4, 5]

1 – [25]

Complement system, immune response

P54764

Ephrin type-A receptor 4

Yes

− 100

5 ↓ [4, 5, 56]

RTK signalling, promiscuous, prevents axonal regeneration, cell adhesion, cell signalling, repair after injury in the nervous system, axonal guiding

Q6MZW2

Follistatin-related protein 4

 

− 75

3 ↓ [4, 5]

1 – [25]

Negative regulation of dendritic spine development and collateral sprouting

P48058

Glutamate receptor 4

Yes

− 50

2 ↓ [4, 5]

2 – [4, 25]

Excitatory synaptic transmission

P01591

Immunoglobulin J chain

 

67

2 ↑ [4], 1 – [5]

Links monomers of IgM or IgA, antigen binding, immune response

Q92876

Kallikrein-6

Yes

− 60

1 ↑ [56]

2 − [–2, 25]

7 ↓ [2, 4, 5, 22, 56, 57]

Serine protease, Indicated in AD, regulation of axon outgrowth after injury, myelination

P32004

Neural cell adhesion molecule L1

Yes

− 75

3 ↓ [4, 5]

1 – [25]

Nervous system development, neuron–neuron adhesion, neuronal migration, axonal growth, synaptogenesis

Q9ULB1

Neurexin-1

 

67

2 ↓ [4, 5]

1 – [4]

Cell surface protein, cell–cell interactions, axon guidance, signal transmission, neurotransmitter release

Q9P2S2

Neurexin-2

 

− 75

3 ↓ [4, 5]

1 – [25]

Neuronal cell surface protein, cell recognition, adhesion, signalling

Q92823

Neuronal cell adhesion molecule

 

− 75

3 ↓ [4, 5]

1 – [25]

Neurite outgrowth. cell–cell contacts between Schwann cells and axons. formation and maintenance of the nodes of Ranvier on myelinated axons.

Q99983

Osteomodulin

Yes

75

3 ↑ [4, 5]

1 – [25]

Biomineralization processes, cell adhesion, extracellular matrix

Q9UHG2

ProSAAS

Yes

− 75

3 ↓ [4, 5]

1 – [25]

Control of the neuroendocrine secretory pathway.

P23468

Receptor-type tyrosine-protein phosphatase delta

Yes

− 100

2 ↓ [4, 5]

Phosphatase, pre- and post-synaptic differentiation of neurons

O00584

Ribonuclease T2

 

100

3 ↑ [4, 5]

Lysosomal degradation of ribosomal RNA

P13521

Secretogranin-2

 

− 57

4 ↓ [4, 5, 22]

3 – [2, 25]

Neuroendocrine secretory granule protein

Q6UXD5

Seizure 6-like protein 2

 

− 50

2 ↓ [4, 5]

2 – [4, 25]

Specialized ER function in neurons?

  1. Relevant details for the selected proteins, such as whether or not they were found in the main protein–protein interaction network in our recent in-depth discovery study [5], their CSF-PR score, studies that found them increased or decreased in MS vs. Non-MS and selected gene ontology terms and keywords related to their function. Arrows pointing down: decreased abundance in MS; arrows pointing up: increased abundance in MS; Dash: no change in abundance between MS and Non-MS
  2. * Proteins found in the main protein interaction network from [4]
  3. ** The score for MS vs. Non-MS calculated by CSF-PR according to the equation described in “Materials and methods” section
  4. *** Multiple datasets can be from the same paper