Glycans as biomarkers of disease Pauline M Rudd, Jane Telford, Jennifer C. Byrne, Barbara Adamcyzk, Radka Saldova Glycobiology Group, National Institute for Bioprocessing Research and Training, Foster Avenue, Mount Merrion, Blackrock, Co.Dublin, Ireland

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Glycans as biomarkers of disease


Pauline M Rudd, Jane Telford, Jennifer

C. Byrne, Barbara Adamcyzk, Radka Saldova


Glycobiology Group, National Institute for Bioprocessing Research and Training, Foster
Avenue, Mount Merrion, Blackrock, Co.Dublin, Ireland


Over half of all proteins are glycosylated, and alterations in glycosylation are common in
both
physiological and pathological processes. Glycan
processing is
, in the first instance,
determined

by
genes

(1)

that code for 600 or so proteins that
are
involved

this important post
-
translational
modification.

H
owever
,

the complex pathways
,

epigenetic factors
(2) and the local environment all
provide a further
means

for fine tuning and diversifying the glycans
enabling them to

play a role in
determin
ing

th
e

locations and

functions of the proteins to which they are attached. Thus in
identifying

changes

of glycosylat
ion in disease

it is imperative to understand the
systems which are perturbed to
generate the altered glycan processing
.
We have set up a strateg
y that provides some insights into

the relationship between
-
omics
(3, 4) and pathways
data as well
enabling
the

identif
ication

and
validat
ion of

potential glycosylated biomarkers
. A

robotic platform

(5)
,

capable of releasing and
labelling glycoproteins in

a 96 well plate format
,

has been developed as a front end to various glycan
separations technologies including HILC and RP HPLC, MS and capillary electrophoresis, chip
technologies and on
-
line combinations of these techniques. Data bases for all of these technologies
are current
ly under construction (
http://glycobase.nibrt.ie/tools.html
).
We have applied this technology
to identify potential serum or CSF glycome markers for
diseases including
Mid
-
Onset Diabetes
of the
Young (MO
DY)
, schizophrenia
(6
), galactosemia

(
7
)
,
juvenile
rheumatoid arthritis

(8)

and various
cancers

(3)
.


1.
Genomics meets glycomics

-

the first GWAS study of human N
-
Glycome identifies HNF1α as a
m
aster regulator of plasma protein fucosylation.

Lauc G, Essafi A, Huffman JE, Hayward Rudd PM,
Rudan I. et al., PLoS Genet. 2010;6(12)


2.
5
-
AZA
-
2'
-
deoxycytidine induced demethylation influences
N
-
glycosylation of secreted glycoproteins
in ovarian cancer.

Saldova R, Dempsey E, Pérez
-
Garay M, Mariño K, Watson JA, Blanco
-
Fernández
A, Struwe WB, Harvey D, Madden SF, Peracaula R, McCann A, Rudd PM. Epigenetics. 2011 1;6(11).

3.
Glycomic and glycoproteomic analysis of serum from patients with stomach cancer reveals
potential markers arising from host defense response mechanisms.

Bones J, Byrne JC, O'Donoghue
N, McManus C, Scaife C, Boissin H,
Nastase A
, Rudd PM. J Proteome Res. 2011
10(3):1246
-
65.

4.
Ultra performance liquid chromatographic profiling of serum N
-
glycans for fast and efficient
identification of cancer associated alterat
ions in glycosylation.

Bones J, Mittermayr S, O'Donoghue N,
Guttman A, Rudd PM. Anal Chem. 2010 Dec 15;82(24):10208
-
15.

5.
A systematic approach to protein glycosylation analysis: a path through
the maze.

Mariño K, Bones
J, Kattla JJ, Rudd PM.

Nat Chem Biol. 2010 Oct;6(10):713
-
23.

6.
Identification of N
-
glycosylation changes in the CSF and serum in patients with schizophrenia.

Stanta JL,

Saldova R, Struwe WB, Byrne JC, Leweke FM, Rothermund M, Rahmoune H, Levin Y,
Guest PC, Bahn S, Rudd PM.

J Proteome Res. 2010 Sep 3;9(9):4476
-
89. Erratum in: J Proteome
Res. 2010 Oct 1;9(10):5510.

7
.
IgG N
-
glycans as potential biomarkers for determining galactose tolerance in Classical
Galactosaemia.

Coss KP, Byrne JC, Coman DJ, Adamczyk B, Abrahams JL, Saldova R, Brown AY,
Walsh O, Hendroff U, Carolan C, Rudd PM, Treacy EP.

Mol Genet Metab. 2012

Feb;105(2):212
-
20.

8.
Multiple juvenile idiopathic arthritis subtypes demonstrate pro
-
inflammatory IgG glycosylation.

Ercan A, Barnes MG, Hazen M, Tory H, Henderson L, Dedeoglu F, Fuhlbrigge RC,

Grom A, Holm IA,
Kellogg M, Kim S, Adamczyk B, Rudd PM, Beth Son M, Sundel RP, Foell D, Glass DN, Thompson
SD, Nigrovic PA.

Arthritis Rheum. 2012 May 1. doi: 10.1002/art.34507. [Epub ahead of print]