group members: wayne christopher, ph.d. bob edgar, ph.d. duncan brown dan holliman
DESCRIPTION
UC Berkeley Phylogenomics Kimmen Sj ö lander http://phylogenomics.berkeley.edu [email protected] Algorithm & tool development for protein structure-function prediction. Investigation of innate immunity in plants and animals: Brian Staskawicz (Plant & Microbial Biology) - PowerPoint PPT PresentationTRANSCRIPT
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UC Berkeley PhylogenomicsKimmen Sjölander http://phylogenomics.berkeley.edu
[email protected] & tool development for protein structure-function
prediction.
Investigation of innate immunity in plants and animals: Brian Staskawicz (Plant & Microbial Biology)Barbara Baker (Plant & Microbial Biology)Richard Michelmore (UCDavis)Dan Portnoy (MCB)Jonathan DG Jones, Sainsbury Laboratory (UK)
Thanks to the National Science Foundation for continued support
Group Members:Wayne Christopher, Ph.D.Bob Edgar, Ph.D.Duncan BrownDan Holliman
And a number of talented undergrads:Jenny Liu, Jason Chan, Eric Roller, Joey Davis, Michael Jurka, Sonia Wu
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Genomics / bioinformatics /computational biology
Biology Mathematics
Computer Science
Chemistry & Pharmacology
Ethics & Law
Engineering
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Algorithm development
• Protein fold prediction and homolog identification
• Phylogenetic inference
• Structure-function analysis and prediction
– Predict structural motifs conferring functional specificity
– Effects of allelic variation on protein function/structure
• Identify structural domains
• Pathway dissection, using prediction of protein-protein
(and other inter-molecular) interactions
BioE 144: “Intro to Protein Informatics”
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What is remote homolog detection?
1MYN
Drosomycin, Antifungal proteinFruit Fly
Antimicrobial Protein 1Common horse chestnut
1BK8
22% Pairwise identity
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1TRY
TRYPSINFusarium Oxysporum (Fungus)
EXFOLIATIVE TOXIN AStaphylococcus aureus (Bacteria)
16% pairwise identity
Homolog recognition in the Twilight ZoneCASP2 Target T0031
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Predicting key positions in proteins
Src homology 2 (SH2) domain
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Panther Molecular Function Classification
of the Human Genome
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The Universal Protein Library (UPL)
U.S. Patent No. 6,128,587
Bayesian Evolutionary Tree Estimation (BETE): U.S. Patent No. 6,128,587
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Trees as predictive models
Subfamilies found by BETE; Tree displayed at subfamily level.
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Berkeley Phylogenomics Group user interface
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Hypothesis-driven vs
Hypothesis-generating approaches
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A Tale of Two Domains
Hidden Markov models, Potassium channels,
and excursions in the Twilight Zone
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Nck_human(adapter protein)
ZA70_human(tyrosine-protein kinase)
Common domains are found in proteins of diverse function and
structure
(PFAM domain identification shown)
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Domain analysis of Voltage-gated K+ channels
TNF-alpha-induced protein B12 and K+ channel tetramerization domain (1T1DA)
-2
-1
0
1
2
3
4
5
1 26 51 76 101
126
151
176
201
226
251
276
301
326
351
376
401
426
451
476
501
MSA columns
log
like
liho
od
Tetramerizationdomain of K+channels
Similar to TNF-alpha-inducedprotein B12 (30seqs)
HMM positions
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There’s a connection...There’s a connection...
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Predictions:
Structure of TNF-alpha induced protein B12 is homologous to K+ channel tetramerization domain
TNF-alpha affects K+ current by
inducing protein B12, which
interacts with the K+ channel at tetramerization domain.
TNF-alpha-induced protein B12 and K+ channel tetramerization domain (1T1DA)
-2
-1
0
1
2
3
4
5
1 29 57 85 113
141
169
197
225
253
281
309
337
365
393
421
449
477
505
MSA columns
log
likel
iho
od
Tetramerization domain ofK+ channels
Similar toTNF-alpha-inducedprotein B12(30 seqs)
1T1DATetramerization Domain
of K+ channels
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Investigation into innate immunity
Brian Staskawicz (Plant & Microbial Biology)Barbara Baker (Plant & Microbial Biology)
Richard Michelmore (UCDavis)Dan Portnoy (MCB)
Jonathan DG Jones, Sainsbury Laboratory (UK)
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Plant and Animal Innate Immunity Mediated by Related Proteins
Cytoplasmic Toll Interleukin 1 Receptor (TIR) domain
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1ICAInsect Defensin AAntibacterial proteinFlesh Fly
1MYN
Antimicrobial Protein 1 Common horse chestnut
1BK8
Drosomycin, Antifungal proteinFruit Fly
Toxin 2 Mexican scorpion(Na+ channel inhibitor)
1CN2
Defensin-related proteins
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Gordon Research Conference on Bioinformatics24-29 Aug 2003 Oxford University
www.grc.org
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UC Berkeley Phylogenomics
Investigation of innate immunity in plants and animals: Brian Staskawicz (Plant & Microbial Biology)Barbara Baker (Plant & Microbial Biology)Richard Michelmore (UCDavis)Dan Portnoy (MCB)Jonathan DG Jones, Sainsbury Laboratory (UK)
Thanks to the National Science Foundation [email protected] http://phylogenomics.berkeley.edu
Group Members:Wayne Christopher, Ph.D.Bob Edgar, Ph.D.Duncan BrownDan Holliman
And a number of talented undergrads:Jenny Liu, Jason Chan, Eric Roller, Joey Davis, Michael Jurka, Sonia Wu