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Genome Project and Bioinformatics. Dr Tan Tin Wee Director Bioinformatics Centre. Human Genome Project.

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genome project and bioinformatics

Genome Project and Bioinformatics

Dr Tan Tin Wee

Director

Bioinformatics Centre

human genome project
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 Subjectsin 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
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
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.
slide5
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
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 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.
slide8
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
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
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.
functional genomics
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
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
Structural Genomics
  • Developing newSoftware to speedup structure eludi-dation.New initiative
  • ModelingDockingStructure Prediction
strategic simulation initiative
Strategic Simulation Initiative
  • Virtual Cell project
  • Biological Pathways
  • Simulation of Flux
  • Prediction of complex outcomes in biolgicalmodels
  • Next big science
exciting challenges ahead for bioinformatics
Exciting Challenges ahead forBioinformatics
  • Software, algorithms, heuristics
  • Global Architecture for resources and research
  • Cross-disciplinary, and multidisciplinary Manpower training challenge
  • Evolution of a new discipline