2010 Annual Report - Institute for Molecular Bioscience - University ...

27 imb researchers: genomics & computational biology
MARK RAGAN
COMPUTATIONAL GENOMICS
WE USE ADVANCED BIOINFORMATIC
and computational methods to investigate
similarities and differences among
genomes and the proteins they encode.
Our goal is to make rigorous quantitative
inferences, at both global and fine scales,
about how genomes, gene and protein
families, regulatory networks and cellular
functions have evolved and diversified. To
deal with very large quantities of data we
use advanced data-management methods,
implement high-throughput computational
workflows, and develop new algorithms,
approaches and software.
Genomes have diversified, both structurally
and functionally, from shared ancestral
states. We develop methods and employ
analytical pipelines to reconstruct the
paths of descent (phylogenomics) and
to study processes of change through
time (evolutionary genomics). We have
characterised pathways of lateral genetic
transfer where genetic information moves
across, not within, genealogical lineages,
and have developed statistically based
approaches to discover genetically
recombined regions and recombination
breakpoints. We are now applying these
approaches to understand genome
diversification and the evolution of
pathogenicity in bacteria.
Another major direction of our research is in
the inference, comparison and analysis of
biomolecular networks in mammalian cells
in normal development and disease. We
are developing scalable approaches that let
us interrogate diverse data types including
molecular sequences (single-nucleotide
polymorphisms and copy-number variation),
protein and RNA structures, metabolic
and signalling pathways, regulatory and
molecular interaction networks, gene
expression profiles, subcellular localisation,
cellular function, orthology maps and
phylogenetic profiles.
For more information on our group and our
research projects, please see www.imb.
uq.edu.au/index.htmlpage=11671
RESEARCH PROJECTS
• Investigating the impact of lateral
genetic transfer on the development of
pathogenicity and virulence in bacteria
• Inferring biomolecular interaction
networks in mammalian cells based on
expression profiles
• Understanding how heterogeneous
genotypes (SNP, CNV) interact with
cellular networks to cause or maintain
disease, particularly cancer
• Abstracting and analysing biomolecular
control networks as graphs
• Fine-scale mapping of orthologous
and paralogous regions of mammalian
genomes
• Studying protein-protein interaction
networks in cellular context
• Computationally discovering novel
miRNA targets in mammalian genomes
KEY PUBLICATIONS
Maetschke, S.R. et al. (Ragan, M.A.
listed as senior author) (2010). A visual
framework for sequence analysis using
n-grams and spectral rearrangement.
Bioinformatics 26: 737-744.
Davis, M.J., Sehgal, M.S., and Ragan,
M.A. (2010). Automatic, context-specific
generation of Gene Ontology slims. BMC
Bioinformatics 11: 498.
Walter, T. et al. (2010). Visualization of
image data from cells to organisms.
Nature Methods 7: S26-S41.
Chan, C.X., Darling, A.E., Beiko, R.G., and
Ragan, M.A. (2009). Are protein domains
modules of lateral genetic transfer PLoS
ONE 4: e4524.
Kassahn, K.S., Dang, V.T., Wilkins, S.J.,
Perkins, A.C., and Ragan, M.A. (2009).
Evolution of gene function and regulatory
control after whole-genome duplication:
comparative analyses in vertebrates.
Genome Research 19: 1404-1418.
Ragan, M.A., and Beiko, R.G. (2009).
Lateral genetic transfer: open issues.
Philosophical Transactions of the Royal
Society of London B: Biological Sciences
364: 2241-2251.
Darling, A.E., Miklós, I., and Ragan, M.A.
(2008). Selection on genome arrangement
in circular bacterial chromosomes. PLoS
Genetics 4: e1000128.
LAB MEMBERS
Research Officers: Dr Melissa Davis
(QFAB), Dr Stefan Maetschke, Dr Chenwei
Wang
Queensland Facility for Advanced
Bioinformatics Senior Team: Jeremy
Barker (CEO), Dr Dominique Gorse
(Technical Manager)
NCI SF Bioinformatics / EMBL Australia
EBI Mirror Team: Dr David Green (Project
Manager), Gavin Graham, Dr Gerald
Hartig
Manager, ARC Centre of Excellence in
Bioinformatics: Lanna Wong
Scientific Programmer: Chikako Ragan
PhD Students: JooYoung Choi, Piyush
Madhamshettiwar, Chang Jin Shin,
Elizabeth Skippington
International Trainees: Alexandra Diem
(Friedrich-Schiller-University Jena), Martin
Simonsen (Aarhus University)
Undergraduate Research Trainee: Ann
Bui
BLAST
Nodes: 831
Edges: 1266
Clustering Coefficient: 0.017
Human Phylome
Nodes: 367
Edges: 493
Clustering Coefficient: 0.013
MACHOS
Homologene
Nodes: 670
Edges: 1005
Clustering Coefficient: 0.010
Inparanoid
A multiple whole-genome alignment of six
strains of Escherichia coli consists of 34
rearranged pieces larger than 1 kb.
Nodes: 503
Edges: 705
Clustering Coefficient: 0.015
CORE