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Genomic Infrastructure Projects
Our group participates in large-scale experimental efforts to generate
landmark datasets describing the organization of biological systems.
We recently published a map of protein-protein interactions in Drosophila
(Giot, Bader et al. Science 2003), which provides what is essentially
a wiring diagram for how the protein components of an insect cell
are organized into protein complexes, pathways, and higher-order
functional groupings. We are now participating in large-scale efforts
to map the entire set of genetic interactions in Saccharomyces cerevisiae
(budding yeast) and to map protein-protein interactions in human.
Computational Analysis of Biological Networks
We develop computational methods to analyze the structure and function
of biological networks on length-scales ranging from atomic-resolution
interactions between biomolecules to topological analysis of pathways.
The techniques we employ include molecular simulation, DNA and protein
sequence analysis using hidden Markov models and related methods,
and statistical physics and computational algorithms for graphs.
Current research areas include computational inference of biological
networks and network evolution, topological analysis of network
robustness, and development of novel algorithms for combined analysis
of heterogeneous data. Active collaborations with experimental groups
permit critical tests of our computational predictions.
Human Disease
An underlying motivation for work in our group is to advance human
health by understanding the genetic and environmental determinants
of human disease. We are using DNA repair in yeast as a model system
to study the molecular mechanisms leading to genome instability
and cancer. The DNA repair machinery is conserved throughout eukaryotes,
and mutations that cause deleterious effects in yeast have been
shown to cause cancer in human. Our second area is infectious disease,
where we are using microbial infection of Drosophila macrophages
as a model system to study innate immunity in human. We provide
bioinformatics and computational biology expertise for a multi-institution
effort using full-genome RNAi to identify Drosophila host factors
relevant to innate immunity and host-pathogen interactions.
Selected Publications
Bader JS, Chaudhuri A, Rothberg JM, Chant J 2004 Gaining confidence
in high-throughput protein interaction networks. Nat Biotech
22: 78-85
Giot L, Bader JS, Brouwer C, Chaudhuri A, Kuang B, Li Y, Hao YL,
Ooi CE, GodwinB, Vitols E, Vijayadamodar G, Pochart P, Machineni
H, Welsh M, Kong Y, Zerhusen B, Malcolm R, Varrone Z, Collis A,
Minto M, Burgess S, McDaniel L, Stimpson E, Spriggs F, Williams
J, Neurath K, Ioime N, Agee M, Voss E, Furtak K, Renzulli R, Aanensen
N, Carrolla S, Bickelhaupt E, Lazovatsky Y, DaSilva A, Zhong J,
Stanyon CA, Finley Jr. RL, White KP, Braverman M, Jarvie T, Gold
S, Leach M, Knight J, Shimkets RA, McKenna MP, Chant J, Rothberg
JM 2003 A protein interaction map of Drosophila melanogaster Science
302: 1727-1736
Bader JS 2003 Greedily building protein networks with confidence.
Bioinformatics. 19: 1869-1874.
Sham P, Bader JS, Craig I, O'Donovan M, Owen M 2002 Efficient association
studies using pooled DNA: promise and pitfalls. Nature Reviews
Genetics 3: 862-871
Bader JS, Sham P 2002 Family-based association tests for quantitative
traits using pooled DNA. Eur J Hum Gen 10: 868-876
Bader JS, Deem MW, Hammond RW, Henck SA, Simpson JW, Rotherberg
JM 2002 A Brownian-ratchet DNA pump with applications to single-nucleotide
polymorphism genotyping. Appl Phys A 74: 1-4
Jawaid A, Bader JS, Purcell S, Cherny SS, Sham P 2002 Optimal selection
strategies for QTL mapping using pooled DNA samples. Eur J Hum
Gen 10: 125-132
Bader JS, Bansal A, Sham P 2001 Efficient SNP-based tests of association
for quantitative phenotypes using pooled DNA. Genescreen 1: 143-150
Bader JS 2001 The relative power of SNPs and haplotypes as genetic
markers for association tests. J. S. Bader. Pharmacogenomics
2: 11-24
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