Presentation in the Human Glycomics Proteomics Disease Initiative (HGPI) session

James C. Paulson

English

Nature Precedings

1HGPI 2006
HGPI Initiative
HUPO Meeting : Long Beach, CA
October 29, 2006
Bioinformatics Approach to
Functional Glycomics
James C. Paulson - The Scripps Research Institute
HGPI 2006
Consortium for Functional Glycomics
Goal:
Define paradigms by which protein-
carbohydrate interactions mediate cell
communication
http://www.functionalglycomics.org
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2HGPI 2006
Attachment of microbial pathogens to
host cell glycans
Virus attachment
and endocytosis
Bacterial
colonization
Toxin
attachment
HGPI 2006
Cell surface GBPs binding pathogen
and glycoprotein glycans
Microbe
Recognition
Glycoprotein 
Targeting
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3HGPI 2006
 Soluble GBPs binding cell surface and
pathogen glycans
Glycoprotein 
lattice
Opsonization
Glycan specific
antibody
HGPI 2006
Cell surface GBPs binding cell surface
glycans
Trans ligand: 
Cell adhesion
Cis ligand:
Receptor signaling
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4HGPI 2006
Protein
Regulating information content of glycans
DNA
RNA
GLYCAN
GLYCOSYLTRANSFERASES
(Protein)
Function
HGPI 2006
Cell type specific expression of glycans
Embryo
J Marth UCSD
Mouse Embryo
Galβ1-3GalNAc
PNA lectin
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5Part. Investigators
•Explore Biology
using tools
•Contribute data
> 180 Institutions
Consortium for Functional Glycomics
Glycan Library
Tools for specificity
analysis and  biology
TSRI
Mouse Phenotype
UC San Diego
Mouse Transgenics
Create & Distribute
KO mice
TSRI
Consortium Databases
MIT
Steering Committee
Analytical
Glycan Profiling
Imperial
College
Glycan Microarray
GBP ligand specificity
Emory Univ.
Gene Microarray
GBP and GT gene
expression
TSRI
I80 Institutions
HGPI 2006
Consortium for Functional Glycomics :
Glycobiology Resources Offered
Specificity of your glycan-
binding protein on microarry
with ~300 glycoprotein and
glycolipid glycans
Glycan array screening
Over 230 carbohydrate
compounds available with
azido or biotin functional
groups
Carbohydrate compounds
Novel knockout mouse
strains with genes ablated
for glycan-binding proteins
Mouse knockout strains
http://www.functionalglycomics.org
Analyze your mRNA on a
custome gene microarray
including 2,000 human
and mouse glyco genes
Glyco-gene microarray
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6HGPI 2006
Bioinformatics
 Implement vision for CFG
databases developed with
the SC, Scientific Cores
and Participating
Investigators.
 Develop interfaces for
acquisition and
dissemination of
Consortium data.
 Develop specialty
databases integrated with
CFG data as resources
for PIs and the scientific
community.
Bioinformatics
Rahul Raman
Ram Sasisekharan
MIT
HGPI 2006
Integration of interfaces for CFG data and
specialty databases
Glycan- 
Transferase DB
Biosynthesis
Glycan 
Structures DB
Structure
Glycan Binding 
Protein DB
Biology
Glycan 
array data
Glycogene
microarray 
data
Analytical
glycomics
data
Mouse 
Phenotype
data
Consortium Data
Specialty Databases
Implemented
Planned
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7HGPI 2006
Integration of interfaces for CFG data and
specialty databases
Glycan 
Structures DB
Structure
Glycan Binding 
Protein DB
Biology
Glycan 
array data
Consortium Data
Specialty Databases
Implemented
Planned
CFG Glycan Microarray  
O
O NH2
Synthetic
Glycans
NHS-activated
glass surface
N
O
O
O
O
+
Stable amide bond
N
H
O
O
O
Standard microarray
robotics
Blixt et al. (2004)
PNAS 101, 17033
QuickTime™ and a
 decompressor
are needed to see this picture.
http://functionalglycomics.org
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8HGPI 2006
Symbol Nomenclature
Key: Gal GlcNAcFucNeuAc GalNAcGlc Man
N-Linked O-Linked
NeuAc!2-6Gal"1-4GlcNAc"1-2Man!1
NeuAc!2-6Gal"1-4GlcNAc"1-2Man!1
Man"1-4GlcNAc"1-4GlcNac-Asn
6
3
6
Fuc!1
NeuAc!2-3Gal"1-4GlcNAc"1
NeuAc!2-3Gal"1
GalNAc!-Thr
6
3
!3
!6
"4"4
!6
!6 "4 "2
!6 "4 "2
!3
!3
"4 "6
"3
Modified IUPAC nomenclature
HGPI 2006
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9HGPI 2006
HGPI 2006
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10
HGPI 2006
HGPI 2006
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11
HGPI 2006
Integration of interfaces for CFG data and
specialty databases
Glycan- 
Transferase DB
Biosynthesis
Glycan 
Structures DB
Structure
Glycan Binding 
Protein DB
Biology
Glycan 
array data
Consortium Data
Specialty Databases
Implemented
Planned
HGPI 2006
Structure variation in N-linked glycans
Type 1 
Extension
Key: Gal GlcNAcFuc GlcAGalNAcGlc Man NeuAc
C Core sequenceE Extension sequenceS Sulfate
C
!4!2
!6
"3
!3
"4
!3
!3
!2
"3
E
E
C
!3
!6
!3
"3
!3
"4
!3
"4
3S
6S
6S
3S
1
"3
!8
!6"6
!2
Type 2 
Extension
E
E
E
E
E
E
E
!4
!6
!4
!2
"6
"3
!4
!2
!4
"6 "6
!6
!4
!2
Complex-Type
Core
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12
HGPI 2006
HGPI 2006
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13
HGPI 2006
Integration of interfaces for CFG data and
specialty databases
Glycan 
Structures DB
Structure
Analytical
glycomics
data
Consortium Data
Specialty Databases
Implemented
Planned
HGPI 2006
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14
HGPI 2006
Glycoproteins Glycolipids
(complemented by
enzyme digests etc)
Glycomics Screening Strategy
HGPI 2006
Glycan Structures Database
Integration with Glycan Analysis Data
MS/MS analysis
GC-MS linkage analysis
Human                                                  Colon           Maldi MS only
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15
HGPI 2006
Glycan structure database
Data exchange with other initiatives
Glycan DB
Glycan DB Glycan DB
Glycan DB Glycan DB
XML format -
Exchanging
Information
HGPI 2006
Forge Alliances with Other Consortia and
Database Organizations
 Identify synergies
with existing
consortia and
databases.
Leverage resources
to mutual benefit.
Develop uniform
standards for
depositing and
sharing data
Steering 
Committee
Participating
Investigators
Scientific
Cores
Other 
Consortia
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HGPI 2006
HGPI 2006
Acknowledgments
Advisory Committee
Elizabeth Neufeld
Ellis Reinherz
Nathan Sharon
Steering Committee
Paul Crocker
Richard Cummings
Anne Dell
Kurt Drickamer
Pamela Marino
Jamey Marth
James Paulson
Steve Rosen
Ram Sasisekharan
Ron Schnaar
Pamela Stanley
Scientific Cores
Ola Blixt
Steve Head
Stuart Haslam
Bo Ma
Sally Orr
Rahul Raman
David Smith
Participating 
Investigators
~300
Sponsors:
NIGMS
Neose Technologies
Kyowa Hakko
Otsuka Phamaceuticals
NRC Ottawa
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Bioinformatics Approach for Functional Glycomics

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Bioinformatics Approach for Functional Glycomics

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