Transcript Bioinformatics Research and Resources at the University of

Introduction to Bioinformatics: Lecture I
An Overview of the Course
Jarek Meller
Division of Biomedical Informatics,
Children’s Hospital Research Foundation
& Department of Biomedical Engineering, UC
JM - http://folding.chmcc.org
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Outline of the outline lecture

Bioinformatics as hypothesis generator for
biomedical research in the postgenomic era
 Bioinformatics at the University of Cincinnati
& Children’s Hospital Research Foundation:
research and resources
 Introduction to Bioinformatics course:
problems and case studies, web and Protein
Modeling Lab resources, syllabus and some
practical issues
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Bioinformatics as hypotheses generator
Making sense of massive amounts of genomic,
proteomic etc. information in order to facilitate
further experiments by data mining and
inference, modeling and computer simulations.
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Some more “precise” definitions
“Roughly, bioinformatics describes any use of
computers to handle biological information”
 “In practice the definition used by most people is
narrower; bioinformatics to them is a synonym for
"computational molecular biology“ -- the use of
computers to characterize the molecular components
of living things.”
 “The mathematical, statistical and computing methods
that aim to solve biological problems using DNA and
amino acid sequences and related information.”
 More: http://bioinfomatics.org
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Other “definitions”
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Subject or body of research – e.g. google
bioinformatics and simply digest the 2 ML (1 ML= 106
Links) or so …
Methods and approaches: computational paradigm in
molecular biology and biomedical research
Institutional boundaries – take a body of research
from all the scientific institutions having
“bioinformatics” in their name
Let us have look at local bioinformatics resources
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Bioinformatics at the UC and CHRF:
Research and Resources
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Pneumocystis Genome Project
Sequencing the genome of a fungal
pathogen causing Pneumocystis
pneumonia: towards novel drug
targets and therapies.
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Melanie Cushion (VA/UC)
George Smulian (VA/UC)
JM
http://pneumocystis.cchmc.org
UC/CHRF sequencing core:
http://dna.chmcc.org
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Microarray-based gene expression studies
Numerous studies on genome-wide
expression profiles to identify interesting
targets and elucidate protein pathways.
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Bruce Aronow (CHRF)
Mario Medvedovic (UC/CHRF)
Yizong Cheng (UC)
CHRF Affymetrix GeneChip core
UC Genomics and Microarray Lab
JM - http://folding.chmcc.org
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GIMM (Gaussian Infinite Mixture
Models) Software (M. Medvedovic)
11113.3, Pauci , 1_Pauci , MTX 0 , XR_unknown
878, Pauci , 2_Poly , MTX 1 , XR_erosions
JM - http://folding.chmcc.org
Individuals (33 patients + 12 controls)
976, Pauci , 1_Pauci , MTX 1 , XR_norm al
9161, Pauci , 1_Pauci , MTX 1 , XR_norm al
7177, Spond, JSPA , MTX 1 , XR_space narrowing
8003, Pauci , 1_Pauci , MTX 0 , XR_unknown
993, Syst, 2_Poly , MTX 1 , XR_space narrowing
9137, Poly, 2_Poly , MTX 0 , XR_space narrowing
19, Pauci , 2_Poly , MTX 1 , XR_space narrowing
912, Syst, 2_Poly , MTX 1 , XR_space narrowing
1081, Poly, 2_Poly , MTX 0 , XR_space narrowing
9272, Poly, 2_Poly , MTX 1 , XR_unknown
1087PB, Poly, 2_Poly , M TX 1 , XR_space narrowing
1073, Syst, 2_Poly , MTX 0 , XR_space narrowing
872, Poly, 2_Poly , MTX 1 , XR_space narrowing
850, Poly, 2_Poly , MTX 1 , XR_erosions
831, Poly, 2_Poly , MTX 1 , XR_erosions
894, Pauci , 2_Poly , MTX 1 , XR_normal
7029, Pauci , 1_Pauci , MTX 0 , XR_norm al
18036, Pauci , 1_Pauci , MTX 0 , XR_norm al
18057, Spond, JAS , MTX 0 , XR_sclerosis
845, Spond, JAS , MTX 0 , XR_space narrowing
1083, Control, na , MTX 0 , XR_ na
...
7113.3, Control, na , MTX 0 , XR_na
9150, Spond, JAS , MTX 0 , XR_sclerosis
7108, Syst, 3_System ic , M TX 1 , XR_normal
813.3, Control, na , MTX 0 , XR_ na
1084, Control, na , MTX 0 , XR_ na
7021.31, Cont rol, na , MTX 0 , XR_ na
18042, Spond, JAS , MTX 0 , XR_sclerosis
7118.3, Control, na , MTX 0 , XR_ na
9264, Pauci , 1_Pauci , MTX 0 , XR_erosions
824, Poly, 2_Poly , MTX 0 , XR_norm al
9245, Spond, JSPA , MTX 0 , XR_space narrowing
1087ctrl, Cont rol, na , MTX 0 , XR_ na
801, Pauci , 2_Poly , MTX 1 , XR_erosions
7149.3, Control, na , MTX 0 , XR_ na
1095, Control, na , MTX 0 , XR_ na
1089, Control, na , MTX 0 , XR_ na
1085, Control, na , MTX 0 , XR_ na
1082, Control, na , MTX 0 , XR_ na
817, Pauci , 1_Pauci , MTX 0 , XR_space narrowing
7206, Pauci , 1_Pauci , MTX 0 , XR_unknown
7145, Pauci , 1_Pauci , MTX 0 , XR_norm al
Clustering algorithms for expression profiles
Medvedovic M and Sivaganesan S; Bayesian infinite mixture model based
clustering of gene expression profiles , Bioinformatics 2002
Medvedovic M, Yeung KY, Bumgarner RE; Bayesian mixture model based
clustering of replicated microarray data, to appear in Bioinformatics 2004
Individual:
Poly-Articular JRA Course
Controls
105 Genes with
Significantly Lower
Expression In
PolyArticular
JRA
242
genes
...
137 Genes with
Significantly
Higher
Expression In
PolyArticular
JRA
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Computational studies of transcription regulation
Jegga AG, Sherwood SP, Carman JW, Pinski AT, Phillips JL, Pestian JP, Aronow BJ;
Detection and visualization of compositionally similar cis-regulatory element clusters in
orthologous and coordinately controlled genes, Genome Research 2002
Detection of Transcription
Factors binding sites 
TRAFAC server
http://trafac.cchmc.org
JM - http://folding.chmcc.org
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Proteomics
Studying protein expression, structure, interactions, pathways etc.
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Rashmi Hedge (CHRF)
 Mark Rance (UC)
 Patt Limbach (UC)
 Bruce Aronow (CHRF)
 Michael Wagner (CHRF)
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JM
HIF-1
VHL
Elongin C
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Elongin B
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Protein expression profiling
Wagner M, Naik D, Pothen A; Protocols for disease classification from mass
spectrometry data, Proteomics 9 (2003)
Wagner M, Naik D, Pothen A, Kasukurti S, Devineni R, Adam B, Semmes O
and Wright Jr G; Computational Protein Biomarker Prediction: A Case
Study for Prostate Cancer, to appear in BMC Bioinformatics (2004)
Searching for disease fingerprints
in mass spec profiles 
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Structural and functional annotations for proteins
R. Adamczak, A. Porollo and J. Meller; Accurate Prediction of Solvent
Accessibility Using Neural Networks Based Regression, Proteins:
Structure, Function and Bioinformatics, to appear (2004)
A. Porollo, R. Adamczak and J. Meller; Polyview: A Flexible Visualization
Tool for Structural and Functional Annotations of Proteins,
Bioinformatics, to appear (2004)
SABLE server
http://sable.cchmc.org
POLYVIEW server
http://polyview.cchmc.org
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Machine learning and pattern recognition
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JM
Michael Wagner
Rafal Adamczak
Mario Medvedovic
Fishing for patterns and fingerprints
that correlate with phenotypes and
biological processes
JM - http://folding.chmcc.org
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Genomic fingerprints of disease states
JM - http://folding.chmcc.org
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Perspectives and future directions
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Integration of individual projects and systems
biology approach
 Predictive medicine using multi-dimensional
fingerprints of disease states, risks and
optimal treatments
 Infrastructure challenges: the Center for
Computational Medicine as a regional hub for
biomedical research
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Summary of current resources
UC Center for Genomics and Bioinformatics
UC NMR Core
UC/CHRF Proteomics Core
UC and CHRF sequencing cores
UC and CHRF microarrays cores
CHRF computational infrastructure
http://genome.uc.edu
http://info.chmcc.org
http://folding.chmcc.org
http://www.cincinnatichildrens.org/research/cores/default.htm
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Web resources and materials for the course
Protein Modeling Lab
Remote access to PML and the Citrix software
All lectures and other materials available electronically from the PML servers
Electronic tests and homework, web submission interfaces
The web site for the Introduction to Bioinformatics course
Updates
http://folding.chmcc.org
http://folding.chmcc.org/protlab/protlab.html
http://folding.chmcc.org/intro2bioinfo/intro2bioinfo.html
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