Humetics 2014 12-10-final
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Transcript of Humetics 2014 12-10-final
.
Dec. 10, 2014
Natal van Riel, Peter [email protected]
Tel. 5506
GEM-Z 3.109
Dept. of Biomedical EngineeringSystems Biology and Metabolic Diseases
@nvanriel
Metabolic Pathways
• Chemical reactions of metabolism can be considered as
organized into metabolic pathways, in which one chemical is
transformed through a series of steps into another chemical, by
a sequence of enzymes
/ biomedical engineering PAGE 210-12-2014
/ biomedical engineering PAGE 310-12-2014
Metabolic Networks
Can we link understanding of metabolism and
biochemistry (incl. modeling)
to the multi-omics data that are collected in
in research projects
and in the clinic of the (near) future
and tendencies towards stratified
and personalized health and healthcare
/ biomedical engineering PAGE 412/10/2014
Computational Biology
TOP-DOWN• Bioinformatics
• Data driven
• Statistics
• Biomodeling
• Hypothesis driven
• Knowledge based
BOTTOM-UP
/ biomedical engineering PAGE 510-12-2014
/ biomedical engineering PAGE 610-12-2014
Genome-Scale Metabolic Models
Genome-Scale Metabolic Models
/ biomedical engineering PAGE 712/10/2014
these models include all known metabolic genes corresponding
to metabolic pathways
2007 Recon1(Duarte 2007 PNAS 104(6): 1777)
2010 Hepatonet(Gille 2010 Mol Syst Biol 6:411)
2013 Recon2(Thiele et al. 2013, Nat Biotech.)
2014 iHepatocyte2322(Mardinoglu 2014_Nat Commun)
Recon 2
• Genome-Scale Metabolic Model
• Total number of reactions 7,440
• Total number of metabolites 5,063
• Number of unique metabolites 2,626
/ biomedical engineering PAGE 810-12-2014
http://humanmetabolism.org/
Applications of the global human metabolic
network
“Genome-scale metabolic network reconstructions provide a
platform to interpret omics data in a biochemically meaningful
manner.”
• Four classes of application:
1. Integration of ‘omics’ data for tissue and cell specific
network reconstruction,
2. Mapping homologous genes for global mammalian network
reconstruction,
3. Contextualization of ‘omics’ data from pathological and
drug-treated states,
4. Simulation of pathological and drug-treated states
/ biomedical engineering PAGE 910-12-2014
/ biomedical engineering PAGE 1010-12-2014
Data Integration and Visualization
/ biomedical engineering PAGE 1110-12-2014
Integration of multi-omics data
/ biomedical engineering PAGE 1210-12-2014
(A) Gene
expression
pattern (4
clusters)
(B) Metabolic
network
expression
overlay
Dharmawardhana et al. Rice 2013, 6:15
Reporter metabolites
—metabolites with significant collective transcriptional response
in the associated enzyme-coding genes
/ biomedical engineering PAGE 1310-12-2014
/ biomedical engineering PAGE 1410-12-2014
Red arrows indicate
overexpression of the
associated genes,
blue arrows indicate
underexpression.
/ biomedical engineering PAGE 1510-12-2014
Application to Urine Metabolomics
Data Integration
/ biomedical engineering PAGE 1612/10/2014
TU/e: Robbin van den Eijnde, Marijke Dermois,
Niels Drost, Peter Hilbers, Natal van Riel
• HUMETICS (HUman METabolic diagnostICS)
• Top-down: bioinformatics
• Bottom-up: modeling and simulation
• Network-based data integration and
analysis (‘middle-out’)
• Genome-Scale Metabolic Model (Recon 2)
• Application: a metabolic perspective on
ADHD and autism (tryptophan pathway)
• APeT (Roosendaal, SME, H. Meijerink)
• Erasmus MC (R.J. Galjaard, Department
of Clinical Genetics)
A metabolic perspective on ADHD, autism
• Neurotransmission is disrupted in most psychiatric disorders
• Serotonergic system malfunctioning
• An underlying metabolic cause
/ biomedical engineering PAGE 1710-12-2014
Yap, et al 2010, J Proteome Res 9(6): 2996
Metabolomics of 24 hour urine
/ biomedical engineering PAGE 1812/10/2014
• Metabolomics
(N=362)
• Recon2, curated for
tryptophan metabolism
• Analysis and
interpretation with
network model
Urine metabolite levels
mapped on the tryptophan
pathway in the metabolic
network and levels visualized
using different colors
Dermois et al, 2014
Network-based analysis
/ biomedical engineering PAGE 1910-12-2014
APeT in collaboration with TU/e
Dermois, van den Eijnde et al
Results from cluster
analysis mapped on the
tryptophan pathway
facilitate biological
interpretation of data
Sluitstuk | Autisme behandelen met
metabolische routeplanner
/ biomedical engineering PAGE 2010-12-2014
http://www.cursor.tue.nl/nieuwsartikel/artikel/sluitstuk-
autisme-behandelen-met-metabolische-routeplanner/
23 januari 2014
/ biomedical engineering PAGE 2110-12-2014