jm - 1 introduction to bioinformatics: lecture i an overview of the course jarek meller jarek...

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Introduction to Bioinformatics: Lecture I An Overview of the Course

Jarek MellerJarek Meller

Division of Biomedical Informatics, Division of Biomedical Informatics, Children’s Hospital Research Foundation Children’s Hospital Research Foundation & Department of Biomedical Engineering, UC& Department of Biomedical Engineering, UC


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


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.


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


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


Bioinformatics at the UC and CHRF: Research and Resources


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


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


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

GIMM (Gaussian Infinite Mixture Models) Software (M. Medvedovic)

Controls

Poly-Articular JRA Course

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242genes

105 Genes withSignificantly Lower

Expression InPolyArticular

JRA

137 Genes withSignificantly

HigherExpression InPolyArticular

JRA

Individual:Individuals (33 patients + 12 controls)


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 TranscriptionFactors binding sites

TRAFAC serverhttp://trafac.cchmc.org


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

Elongin B

Elongin C

V H L


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


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 serverhttp://sable.cchmc.org

POLYVIEW serverhttp://polyview.cchmc.org


Machine learning and pattern recognition

JM Michael Wagner Rafal Adamczak Mario

Medvedovic

Fishing for patterns and fingerprints that correlate with phenotypes andbiological processes


Genomic fingerprints of disease states


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


Summary of current resources

http://genome.uc.eduhttp://info.chmcc.orghttp://folding.chmcc.orghttp://www.cincinnatichildrens.org/research/cores/default.htm

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


Web resources and materials for the course

http://folding.chmcc.orghttp://folding.chmcc.org/protlab/protlab.htmlhttp://folding.chmcc.org/intro2bioinfo/intro2bioinfo.html

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

jm - 1 introduction to bioinformatics: lecture i an overview of the course jarek meller jarek...

Documents

medvedovicjm http

ucjm http

orgjm http

genome research

bioinformatics course

narrower bioinformatics

resources jm http

body of research