Bioinformatics Research and Resources at the University of
Download
Report
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
1
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
JM - http://folding.chmcc.org
2
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.
JM - http://folding.chmcc.org
3
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
JM - http://folding.chmcc.org
4
Other “definitions”
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
JM - http://folding.chmcc.org
5
Bioinformatics at the UC and CHRF:
Research and Resources
JM - http://folding.chmcc.org
6
Pneumocystis Genome Project
Sequencing the genome of a fungal
pathogen causing Pneumocystis
pneumonia: towards novel drug
targets and therapies.
Melanie Cushion (VA/UC)
George Smulian (VA/UC)
JM
http://pneumocystis.cchmc.org
UC/CHRF sequencing core:
http://dna.chmcc.org
JM - http://folding.chmcc.org
7
Microarray-based gene expression studies
Numerous studies on genome-wide
expression profiles to identify interesting
targets and elucidate protein pathways.
Bruce Aronow (CHRF)
Mario Medvedovic (UC/CHRF)
Yizong Cheng (UC)
CHRF Affymetrix GeneChip core
UC Genomics and Microarray Lab
JM - http://folding.chmcc.org
8
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
9
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
10
Proteomics
Studying protein expression, structure, interactions, pathways etc.
Rashmi Hedge (CHRF)
Mark Rance (UC)
Patt Limbach (UC)
Bruce Aronow (CHRF)
Michael Wagner (CHRF)
JM
HIF-1
VHL
Elongin C
Elongin B
JM - http://folding.chmcc.org
11
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
JM - http://folding.chmcc.org
12
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
JM - http://folding.chmcc.org
13
Machine learning and pattern recognition
JM
Michael Wagner
Rafal Adamczak
Mario Medvedovic
Fishing for patterns and fingerprints
that correlate with phenotypes and
biological processes
JM - http://folding.chmcc.org
14
Genomic fingerprints of disease states
JM - http://folding.chmcc.org
15
Perspectives and future directions
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
JM - http://folding.chmcc.org
16
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
JM - http://folding.chmcc.org
17
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
JM - http://folding.chmcc.org
18