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Genome Project and
Bioinformatics
Dr Tan Tin Wee
Director
Bioinformatics Centre
Human Genome Project
The primary goals of the program are to understand
the nature of complex relationships among genes
and the proteins for which they encode, and the
biological functions of these proteins in the whole
organism
• Human GenomeResearch,
Protecting Human Subjects
in Research,
• Microbial Genome Research,
• Health Effects Research,
• Structural Biology, and
• Bioinformatics Infrastructure.
• http://www.ornl.gov/hgmis/
- good introduction
The Human Genome Program of
the US DOE
• Human Genome Project started as US component 1990
US$3billion 15-year effort to find the estimated 80,000
human genes and determine the sequence of the 3-billion
DNA building blocks that underlie all life's diversity.
• A new goal focuses on identifying regions of the human
genome that differ from person to person. Our DNA
sequences are estimated to be 99.9% identical genetically these DNA sequence variations can have a major impact
on how our bodies respond to disease; environmental
insults, such as bacteria, viruses, and toxins; and drugs and
other therapies.
• http://www.er.doe.gov/production/ober/HELSRD_top.html
Goals of HGP cont'd
• exploring the functions of human genes using methods that
include comparing human DNA sequences with those from
organisms such as the laboratory mouse and yeast;
• addressing the ethical, legal, and
social issues surrounding genetic
tools and data;
• developing the computational
capability to collect, store, and
analyze DNA data; and
• developing interdisciplinary
training programs for future
genomics scientists.
• Genes mapped and identified. According to the Genome
Database (GDB), the public repository for human genome
mapping information, over 7600 genes had been mapped to
particular chromosomes in January 1999
• Tens of thousands of human gene fragments have been identified
as expressed sequence tags (ESTs)
• Physical Mapping. The physical mapping goal is to establish a
marker every 100,000 bases across each chromosome (about
30,000 markers). The most complete map yet was published in
summer 1997 and featured about 8000 landmarks
• Sequencing. Roughly 5% of the human genome has been
sequenced so far.
– JGI for high-throughput production sequencing
– silicon "DNA chip" holding tens of thousands of short sequences
• http://www.ornl.gov/hgmis/faq/faqs1.html
http://www.gene.ucl.ac.uk/hugo/
• At least 18 countries have established human genome research
programs. Some of the larger programs are in Australia, Brazil,
Canada, China, Denmark, European Union, France, Germany,
Israel, Italy, Japan, Korea, Mexico, Netherlands, Russia,Sweden,
United Kingdom, and the United St ates.
• over 1000 members representing over 50 countries. HUGO
maintains three regional offices, HUGO Americas, HUGO Europe
and HUGO Pacific
• Coordination role for HGP scientists
• Glossary: http://www.ornl.gov/hgmis/publicat/glossary.html
• http://www.phrma.org/genomics/lexicon/index.html
Bioinformatics and
Computational Biology in HGP
• BioInformatics is the creation, development, and operation of
biological databases and other computing tools to collect,
organize, and interpret biological data.
• Improve content and utility of databases.
• Develop better tools for data generation,capture, and annotation.
• Develop and improve tools and databases for comprehensive
functional studies.
• Develop and improve tools for representing and analyzing
sequence similarity and variation.
• Create mechanisms to support effective approaches for
producing robust, exportable software that can be widely shared.
• Improve current databases and develop newdatabases and
better tools for data generation and capture and
comprehensive functional studies.
• Continued investment in current and new databases and
analytical tools is critical to the success of the Human
Genome Project and to the future usefulness of the data.
Databases must be structured to adapt to the evolving
needs of the scientific community and allow queries to be
answered easily. Planners suggest developing a human
genome database analogous to model organism databases
with links to phenotypic information. Also needed are
databases and analytical tools for the expanding body of
gene expression and function data, for modeling complex
biological networks and interactions, and for collecting and
analyzing sequence variation data.
Genomics
• Genome: All the genetic material in the chromosomes of a
particular organism; its size is generally given as its total
number of base pairs.
• Genomics: the study of genes and their function. Recent
advances in genomics are bringing about a revolution in our
understanding of the molecular mechanisms of disease,
including the complex interplay of genetic and environmental
factors. Genomics is also stimulating the discovery of
breakthrough healthcare products by revealing thousands of
new biological targets for the development of drugs, and by
giving scientists innovative ways to design new drugs,
vaccines and DNA diagnostics. Genomics-based therapeutics
include "traditional" small chemical drugs, protein drugs, and
potentially gene therapy.
DNA Chips www.affymetrix.com
• GeneChip Technology GeneChip
technology can accelerate genomics studies
in the following three areas:
• Expression Analysis allows you to generate accurate, reproducible data on
demand for the identification and validation of novel drug targets, the assessment of
toxicology profiles and other biological assays. available today for human, mouse,
yeast and other organisms.. toxicology and pharmacogenomics.
• Genotyping By minimizing the labor and time required to run an assay,
GeneChip SNP mapping assays accelerate the association of polymorphisms with
disease, understanding the mechanisms that lead to disease, and monitoring patient
response to treatment.
• Disease Management Through targeted sequence analysis, GeneChip probe
arrays facilitate research into more cost-efficient patient management for diseases
such as cancer and AIDS. As more associations between mutations and therapeutic
responses are understood, the number of applications in which complex genetic
information is useful in making patient treatment decisions is expected to rapidly
increase.
Laboratory Information
Management Systems (LIMS)
Functional Genomics
• Expand support for current approaches and innovative
technologies.
• Efficient interpretation of the functions of human genes
and other DNA sequences requires developing the
resources and strategies to enable large-scale investigations
across whole genomes. A technically challenging first
priority is to generate complete setsof full-length cDNA
clones and sequences for humanand model organism
genes. Other functional genomics goals include studies
into gene expression and control, creation of mutations that
cause loss or alteration of function in nonhuman
organisms, and development of experimental and
computational methods for protein analyses.
Comparative Genomics
• Obtain complete genomic sequences for C. elegans (1998),
Drosophila (2002), and mouse (2008).
• A first clue toward identifying and understanding the
functions of humangenes or other DNA regions is often
obtained by studying their parallels in nonhuman genomes.
To enable efficient comparisons, complete genomic
sequences already have been obtained for the bacterium E.
coli, the yeast S. cerevisiae, and the roundworm and work
continues on sequencing the genomes of the fruit fly, and
mouse. Planners note that other genomes will need to be
sequenced to realize the full promise of comparative
genomics, stressing the need to build a sustainable
sequencingcapacity.
Structural Genomics
• Developing new
Software to speed
up structure eludidation.
New initiative
• Modeling
Docking
Structure Prediction
Strategic Simulation Initiative
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Virtual Cell project
Biological Pathways
Simulation of Flux
Prediction of complex
outcomes in biolgical
models
• Next big science
Exciting Challenges ahead for
Bioinformatics
• Software, algorithms, heuristics
• Global Architecture for resources and
research
• Cross-disciplinary, and multidisciplinary
Manpower training challenge
• Evolution of a new discipline