Chi-Cheng Lin, Ph.D. Associate Professor Department of Computer Science Winona State University – Rochester Center Introduction to Bioinformatics

2 Outline What is Bioinformatics Human Genome Project Application of Bioinformatics References Acknowledgement: The presentation includes adaptations from DOE’s “Human Genome Project and Beyond Primer” and Dr. Yan Asmann’s (Mayo Clinic) lecture notes

3 Bioinformatics Living things have the ability to store, utilize, and pass on information Bioinformatics strives to –determine what information is biologically important –decipher how it is used to precisely control the chemical environment within living organisms

4 What is Bioinformatics The combination of Biology and Informatics Originally refers to the use of computational tools to organize and analyze genetic and protein sequence data (first coined by Dr. Hwa Lim in 1988)

5 NCBI’s Definition of Bioinformatics NCBI (National Center for Biotechnology Information, –“Bioinformatics is the field of science in which biology, computer science, and information technology merge to form a single discipline.” –“The ultimate goal of the field is to enable the discovery of new biological insights as well as to create a global perspective from which unifying principles in biology can be discerned.”

6 Human Genome Project

7 Goals include –Identify genes in human DNA –Determine sequence making up human DNA –Store this information in databases –Improve tools for data analysis –Etc. Milestone –April 2003: HGP sequencing is completed and Project is declared finished two years ahead of schedule

8 Interesting Numbers of Human Genome 3 billion: –Number of chemical nucleotide bases (A, C, T, and G) the human genome contains 3 million: –Locations where single-base DNA differences occur in humans 2.4 million: –Number of bases the largest known human gene consists of (the average gene consists is 3000 bases) 30,000: –The total number of genes estimated (much lower than previous estimates of 80,000 to 140,000)

9 Interesting Numbers of Human Genome 99.9% –Fraction of nucleotide bases are exactly the same in all people 50% –Fraction of functions are unknown for over of discovered genes 2% –Fraction of genome codes for proteins (the others: “junk” DNA) 9%, 11%, 26%, 28%, 45%, 83%, 89%, and 95% –The percentage of genes E. coli, rice, roundworm, yeast, fruit fly, zebrafish, mouse, and chimpanzee share with human, respectively.

10 How does the human genome stack up? OrganismGenome Size (Bases) Estimated Genes Human (Homo sapiens)3 billion30,000 Laboratory mouse (M. musculus) 2.6 billion30,000 Mustard weed (A. thaliana)100 million25,000 Roundworm (C. elegans)97 million19,000 Fruit fly (D. melanogaster)137 million13,000 Yeast (S. cerevisiae)12.1 million6,000 Bacterium (E. coli) 4.6 million3,200 Human immunodeficiency virus (HIV) Humans share most of the same protein families with worms, flies, and plants!

11 Anticipated Benefits of Genome Research Molecular Medicine Microbial Genomics Bioarchaeology, Anthropology, Evolution, and Human Migration DNA Identification (Forensics) Agriculture, Livestock Breeding, and Bioprocessing

12 ELSI: Ethical, Legal, and Social Issues Privacy and confidentiality of genetic information. Fairness in the use of genetic information by insurers, employers, courts, schools, adoption agencies, and the military, among others. Psychological impact, stigmatization, and discrimination due to an individual’s genetic differences. Reproductive issues including adequate and informed consent and use of genetic information in reproductive decision making. Clinical issues including the education of doctors and other health-service providers, people identified with genetic conditions, and the general public about capabilities, limitations, and social risks; and implementation of standards and quality ‑ control measures. U.S. Department of Energy Genome Programs, Genomics and Its Impact on Science and Society, 2003

13 ELSI Issues (cont.) Uncertainties associated with gene tests for susceptibilities and complex conditions (e.g., heart disease, diabetes, and Alzheimer’s disease). Fairness in access to advanced genomic technologies. Conceptual and philosophical implications regarding human responsibility, free will vs genetic determinism, and concepts of health and disease. Health and environmental issues concerning genetically modified (GM) foods and microbes. Commercialization of products including property rights (patents, copyrights, and trade secrets) and accessibility of data and materials. U.S. Department of Energy Genome Programs, Genomics and Its Impact on Science and Society, 2003

14 Mike Thompson, Detroit, Michigan -- from The Detroit Free Press Source:

15 Future Challenges: What We Still Don’t Know Gene number, exact locations, and functions Gene regulation DNA sequence organization Chromosomal structure and organization Noncoding DNA types, amount, distribution, information content, and functions Coordination of gene expression, protein synthesis, and post-translational events Interaction of proteins in complex molecular machines Predicted vs experimentally determined gene function Evolutionary conservation among organisms Protein conservation (structure and function) Proteomes (total protein content and function) in organisms Correlation of SNPs (single-base DNA variations among individuals) with health and disease Disease-susceptibility prediction based on gene sequence variation Genes involved in complex traits and multigene diseases Complex systems biology including microbial consortia useful for environmental restoration Developmental genetics, genomics

16 Tackle Future Challenges: Bioinformatics High volume of data to store, compute, and analyze Huge amount of information to retrieve, interpret, and visualize Complex system to study, model, and simulate THAT’S WHY BIOINFORMATICS IS ESSENTIAL!!

17 The ‘omic’ Revolution Bioinformatics has been split into various subjects: –Genomics – the sequencing and annotation of genomes –Comparative genomics – the comparison and characterisation of genomes of different species to identify genes and their functions and to investigate evolutionary history –Functional and structural genomics – the study of gene expression and protein structure and function –Proteomics – the description of the complete set of proteins a particular genome codes for –Others – Computational Biology (protein structure, protein folding), pharmacogenomics, microarray and proteomics data management and analysis, mutation and diseases, human migration pattern, medical informatics…

18 Drew Sheneman, New Jersey -- The Newark Star Ledger Source: Genome Sequencing

19 Human Migration Patterns using Mitochondrial DNA Sequences

20 Human Migration Patterns using Mitochondrial DNA Sequences Higher mutation rates (2.5/site/Myr), more than 10 time higher than nuclear DNA rate Mitochondrial sequence variations determine human family tree G A G A G A TG G A GG A GTA Sequence Collection Sequence Alignment Profiles of Mutations Phylogenetic analysis

21 Medicine and the New Genetics Anticipated Benefits: –Improved diagnosis of disease –Earlier detection of genetic predispositions to disease –Rational drug design –Gene therapy and control systems for drugs –Personalized, custom drugs Gene Testing  Pharmacogenomics  Gene Therapy

22 Pharmacogenomics: the study of how an individual's genetic inheritance affects the body's response to drugs Benefits of pharmacogenomics: Genetic testing before prescribing drugs Dose-selection based on genetic variations Drugs tailor-made to each patients However, the application of pharmacogenomics in medical practice is very limited today, because of the limited genetic information from a large population

23 References NCBI (National Center for Biotechnology Information) homepagehttp:// NCBI Science Primer Human Genome Project Information enome/home.shtml (esp. link to the Education module) enome/home.shtml The Human Genome Project and Beyond Primer enome/publicat/primer2001/primer.ppt enome/publicat/primer2001/primer.ppt