Chapter 7:
Systems Biology
Guest Lecture
Caroline Rempe
February 11, 2016
Discussion Questions
1.
What is the definition of plant systems biology?
2.
How are plant systems biology studies typically conducted,
and why?
3.
What are plant genomics, transcriptomics, proteomics, and
metabolomics?
4.
What is bioinformatics? How can bioinformatics be used to
help a systems‐level understanding of plants?
What is systems biology?
Definitions
System:
“a regularly interacting or interdependent group of
components forming a unified whole.”
-Ludwig von Bertallanfy (1950)
Plant Systems Biology:
“the study of the interactions and dynamic behaviors of the
constitutive components of a plant system under different
conditions, and the establishment of methods and models to
monitor and control cellular responses to developmental
stages, genetic perturbations, and environmental changes.”
-Liu and Stewart pg. 157
Definitions
System:
“a regularly interacting or interdependent group of
components forming a unified whole.”
-Ludwig von Bertallanfy (1950)
Plant Systems Biology:
“the study of the interactions and dynamic behaviors of the
constitutive components of a plant system under different
conditions, and the establishment of methods and models to
monitor and control cellular responses to developmental
stages, genetic perturbations, and environmental changes.”
-Liu and Stewart pg. 157
Figure 7.1 Illustration of a traditional reductionist approach and an integrative approach
used in systems biology (modified from Krepper 2012).
Emergence
Figure 7.5
How are plant systems biology
studies typically conducted?
An Approach to Systems Biology
Figure 7.6. Liu and Stewart
Example:
Systems biology approach can
identify longevity genes.
Environment
Righetti et al. Inference of Longevity-Related Genes from a Robust Coexpression
Network of Seed Maturation Identifies Regulators Linking Seed Storability to Biotic
Defense-Related Pathways. Plant Cell. 2015 Oct;27(10):2692-708.
Selected Results
“Transcripts with expression profiles
correlating with the acquisition of longevity”
Longevity module
What are plant genomics,
transcriptomics, proteomics,
and metabolomics?
‘Omics
Genomics
Sequencing Technologies:
Sanger
DNA Microarray
Solanum Comersonii
draft genome,
Aversano et al. 2015
Next Generation Sequencing:
454 pyrosequencing
Illumina
PacBio
Oxford Nanopore
PacBio Sequencing
Wetterstrand KA. DNA Sequencing Costs: Data from the NHGRI Genome Sequencing
Program (GSP) Available at: www.genome.gov/sequencingcosts. Accessed Jan. 30, 2016.
Is it useful to look at
transcriptome data when you
already have genomic data?
Yes! Genes are differentially expressed
Righetti et al. 2015 Supplemental Fig. 4A
Transcriptomics Workflow
Sequencing
AAA
RNA
TTT
cDNA
Proteomics
Lan et al. 2012
Proteomics Workflow
Mass Spectrometry
Figure 7.13
Metabolomics
KEGG
Metabolomics Workflow
1. Separation
• Gas chromatography
• Liquid chromatography
• Capillary electrophoresis
http://www.intechopen.com
2. Identification
• Nuclear magnetic resonance
• Mass spectrometry
• Spectroscopy
What do we do with all this
data?
-Google definition
What is bioinformatics?
Bioinformatics
Sequence data
(genomics,
transcriptomics,
proteomics)
Structural data
(protein, chemical)
Pathway data
(metabolic flux)
“store, retrieve,
organize, analyze,
interpret, and visualize
biological data.”
-Liu and Stewart pg. 172
Select Bioinformatics Resources
Interdisciplinary Nature of
Systems Biology
Mathematics
Engineering
Systems Biology
Chemistry
Computer Science
Biology
Bioinformatics
Example Systems Biology Study
Assess the metabolic effects of Arabidopsis single gene
perturbations in order to:
-characterize genes with unknown functions
-assess net effects of genetic perturbations
Methods Overview
Genome-based
metabolic model
AraCyc
Selection of genes for mutant
generation
Metabolomics on 11
mass spectrometry
platforms:
7 Targeted
4 Untargeted
Select Data
Expected and observed results with
functionally known gene
Genes with changing
expression tend to
cluster
Results Summary
• Generally, most mutants affected less than 10 metabolites
• Most affected metabolites were clustered in the network, possibly
from being in the same pathway
• 23% of mutants had no detectable metabolic change from wild type
• Not able to determine function of proteins of unknown function
• Metabolomics may still be useful to assess impacts of genetic
modification, especially if more metabolites can be identified
Limitations
Robustness of metabolic system may minimize metabolic shifts
38% of identified chemicals were missing from AraCyc data
Future: Better Predictive
Modeling?
?
Fill in data gaps
Summary of Systems Biology
Integrative
Interdisciplinary