1. Introduction to Bioinformatics Yana Kortsarts References: An Introduction to Bioinformatics Algorithms bioalgorithms.info

2. What is Bioinformatics? Bioinformatics is a relatively new interdisciplinary field that integrates computer science, mathematics, biology, and information technology to manage, analyze, and understand biological, biochemical and biophysical information. Bioinformatics is a computational science and the subset of larger field of Computational Biology.

3. What is Bioinformatics? Bioinformatics is the use of computers to study biology Bioinformatics is the science of using information to understand biology Bioinformatics is integration of information technology (IT) and biology Bioinformatics is the development of computational methods for studying structure, function and evolution of genes, proteins and whole genomes

4. Course Curriculum Ethics, Computing and Genomics Review of Molecular Biology and Biochemistry Concepts  DNA and protein structure  Gene expression (transcription and translation)  Molecular Biology Central Dogma Biological Research on the Web  Public Biological Databases and Data Formats  Searching Biological Databases

5. Course Curriculum Introduction to Bioinformatics Algorithms  Sequence alignments, scoring, gaps  Algorithm Design Techniques: Exhaustive Search, Dynamic Programming  The Needleman and Wunsch Algorithm  The Smith-Waterman Algorithm  Introduction to BLAST  Multiple Sequence Alignment  Phylogenetic Trees Introduction to Python and Biopython in UNIX environment

6. Some Terminology Cell is a primary unit of life Cell consists of molecules, chemical reactions and a copy of the genome for that organism All life on this planet depends on three types of molecules: DNA, RNA and proteins

7. Some Terminology DNA  Holds information on how cell works RNA  Acts to transfer short pieces of information to different parts of cell  Provide templates to synthesize into protein Proteins  Form enzymes that send signals to other cells and regulate gene activity  Form body’s major components (e.g. hair, skin, etc.)

8. DNA - Deoxyribonucleic Acid Genetic material Consists of two long strands Each strand is made of:  Phosphates  Sugar  Nucleotides A (adenine) G (guanine) C ( cytosine) T (thymine)

9. DNA – Double Helix Structure

10. Discovery of DNA DNA Sequences  Chargaff and Vischer, 1949 DNA consisting of A, T, G, C  Adenine, Guanine, Cytosine, Thymine  Chargaff Rule Noticing #A  #T and #G  #C  A “ strange but possibly meaningless ” phenomenon. Wow!! A Double Helix  Watson and Crick, Nature, April 25, 1953   Rich, 1973 Structural biologist at MIT. DNA ’ s structure in atomic resolution. Crick Watson 1 Biologist 1 Physics Ph.D. Student 900 words Nobel Prize

11. Watson & Crick – “…the secret of life” Watson: a zoologist, Crick: a physicist “In 1947 Crick knew no biology and practically no organic chemistry or crystallography..” – www.nobel.sewww.nobel.se Applying Chagraff’s rules and the X-ray image from Rosalind Franklin, they constructed a “tinkertoy” model showing the double helix Their 1953 Nature paper: “It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.” Watson & Crick with DNA model Rosalind Franklin with X-ray image of DNA

12. DNA: The Basis of Life Deoxyribonucleic Acid (DNA)  Double stranded with complementary strands A-T, C-G DNA is a polymer  Sugar-Phosphate-Base  Bases held together by H bonding to the opposite strand

13. DNA, continued Phosphate Base (A,T, C or G) http://www.bio.miami.edu/dana/104/DNA2.jpg Sugar

14. DNA, continued DNA has a double helix structure. However, it is not symmetric. It has a “forward” and “backward” direction. The ends are labeled 5’ and 3’ after the Carbon atoms in the sugar component. 5’ AATCGCAAT 3’ 3’ TTAGCGTTA 5’ DNA always reads 5’ to 3’ for transcription replication

15. Double helix of DNA

16. The Central Dogma of Molecular Biology Information has been transferred from DNA (information storage molecule) to RNA (information transfer molecule) to a specific protein (a functional, non-coding product) DNARNAProtein transcriptiontranslation

17. DNA, RNA, and the Flow of Information TranslationTranscription Replication

18. Central Dogma (DNA  RNA  protein) The paradigm that DNA directs its transcription to RNA, which is then translated into a protein. Transcription (DNA  RNA) The process which transfers genetic information from the DNA to the RNA. Translation (RNA  protein) The process of transforming RNA to protein as specified by the genetic code.

19. RNA RNA is similar to DNA chemically. It is usually only a single strand. T(hyamine) is replaced by U(racil) Some forms of RNA can form secondary structures by “pairing up” with itself. This can have change its properties dramatically. DNA and RNA can pair with each other. http://www.cgl.ucsf.edu/home/glasfeld/tutorial/trna/trna.giftRNA linear and 3D view:

20. More Terminology Transcription of DNA  DNA transcribed into RNA  RNA exits as a single-strand unit and as a double-helix as well  RNA consist of A, C, G and U (uracil) Types of RNA  Messenger RNA – mRNA  Transfer RNA – tRNA  Ribosomal RNA – rRNA

21. More Terminology Translation of Messenger RNA (mRNA):  mRNA is translated into protein Proteins:  linear polymers built from amino acids The transfer of information from DNA to specific protein via RNA takes place according to the genetic code.  The RNA sequence is divided into blocks of three letters  This block is called CODON  Each codon corresponds to the specific amino acid

22. More Terminology Four different nucleotides are used to build DNA and RNA molecules – A, G, C, T and A, G, C, U 20 different amino acids are used in protein synthesis Four nucleotides can be arranged in 64 different combinations of three. There are 64 = 4*4*4 different codons Some codons are redundant and some have special function – to terminate the translation process

23. Translation The process of going from RNA to polypeptide. Three base pairs of RNA (called a codon) correspond to one amino acid based on a fixed table. Always starts with Methionine and ends with a stop codon

24. Cell Information: Instruction book of Life DNA, RNA, and Proteins are examples of strings written in either the four-letter nucleotide of DNA and RNA (A C G T/U) or the twenty-letter amino acid of proteins. Each amino acid is coded by 3 nucleotides called codon. (Leu, Arg, Met, etc.)

25. Protein Synthesis: Summary There are twenty amino acids, each coded by three- base-sequences in DNA, called “codons”  This code is degenerate The central dogma describes how proteins derive from DNA  DNA  mRNA  (splicing?)  protein The protein adopts a 3D structure specific to it’s amino acid arrangement and function

26. Proteins Complex organic molecules made up of amino acid subunits 20 different kinds of amino acids. Each has a 1 and 3 letter abbreviation. http://www.ncbi.nlm.nih.gov/Class/MLACours e/Modules/MolBioReview/iupac_aa_abbreviat ions.html http://www.ncbi.nlm.nih.gov/Class/MLACours e/Modules/MolBioReview/iupac_aa_abbreviat ions.html Proteins are often enzymes that catalyze reactions. Also called “poly-peptides” *Some other amino acids exist but not in humans.