1. Bioinformatics Ch1. Introduction 阮雪芬 2002, Oct 17 NTUST www.ntut.edu.tw/~yukijuan/lectures/bioinfo/Oct17.ppt

2. Outline  A scenario  Life in space and time  Dogmas: central and peripheral  Observable and data archives

3. Traditional and Current Biology  Traditionally, biology has been an observational science.  Now, biology has been converted into deductive science.

4. The Data of Bioinformatics  Very very large amount  Nucleotide sequence databanks contain 16 x 10 9 bases  The full three-dimensional coordinates of proteins of average length ~400 residues: 16000 entries  Not only are the individual databanks large, but their sizes are increasing as a very high rate.

5. GenBank

6. Goals  “ Saw life clearly and saw it whole ”  To interrelate sequence, three- dimensional structure, interactions, and function of individual proteins, nucleic acids and protein-nucleic acid complexes Understand integrative aspects of the biology of organisms

7. Goals  To deduce events in evolutionary history.  To support application to medicine, agriculture and other scientific fields.

8. A Scenario

9. Imagine a Crisis (1)  A new biological virus creates an epidemic of fatal disease in humans or animals Laboratory scientists will isolate its genetic material- a molecule of nucleic acid and determine the sequence. Computer program will then take over

10. Imagine a Crisis (2) Screening this new genome against a data bank of all know genetic messages Developing antiviral therapies: virus contain protein molecules which are suitable targets, for drugs that will interfere with viral structure or function

11. Imagine a Crisis (3) From the viral DNA sequences Protein sequence Computer program

12. Imagine a Crisis (4) From amino acid sequences Three-dimensional structure Computer program

13. Homology Modelling Data bank will be screened for related proteins of know structures Structure will be predicted A B Computer program

14. Ab initio No related protein of known structure is found Ab initio Predicting the structure

15. Design Therapeutic Agents Knowing the viral protein structure Design therapeutic agents

16. Life in space and time

17. In Space  Biosphere  Ecosystem  Darwinian selection or genetic drift Natural mutationThe recombination of genes in sexual reproduction Direct gene transfer The generation of variants

18. In Space Ecosystem Species Cell Nuclei, organelles and cytoskeleton Molecules

19. In Time  A history of life 3.5 billion years

20. Dogmas: Central and Peripheral

21. Central Dogmas  1957, Crick 提出中心教條 ” DNA 製造 RNA ， RNA 製造蛋白質 ”  中心教條大體上是對的，但也有些需要修正 有許多 RNA 病毒： RNA  DNA  RNA  Protein 跳躍基因 真核細胞 RNA 需要經過剪接 不只蛋白質具酵素功能，某些 RNA 也具酵素功能 某些基因可經不同的轉錄起始點或不同的剪接方式， 製備出多種 RNA ，而轉錄成功能不同的蛋白質

22. 真核細胞 RNA 需要經過剪接

23. 不只蛋白質具酵素功能，某些 RNA 也具 酵素功能 First identified in plant virus

25. Purines and Pyrimidines

26. The Strand in the Double-helix are Antiparalle 5’5’ 3’3’ 3’3’ 5’5’

28. Paradigm DNA sequence Protein sequence Protein structure Protein function determines Most of the organized activity of bioinformatics has been focused on the analysis of the data related to these processes

29. Observable and Data Archives

30. A Databank  An archive of information  A logical organization  Structure of that information  Tools to gain access to it

31. A Databank in Molecular Biology  Archival databanks of biological information DNA and protein sequence Nucleic acid and protein structure Databanks of protein expression

32. A Databank in Molecular Biology  Derived Databanks Sequence motifs Mutations and variants in DNA and protein sequences Classification and relationships  Bibliographic Databanks  Databanks of web sites Databanks of databanks containing biological information Links between databanks

33. The Mechanism of Access to a Databank is  the Set of Tools for answering Question Such as: Does the databank contain the information I require? How can I assemble information from the databank in a useful form? Indices of databanks are useful in asking ” Where can I find some specific piece of information? ”

34. Give a sequence or fragment of a sequence Find sequence in the database that are similar to it A central problem in bioinformatics A Variety of Possible Kinds of Database Queries Can Arise in Bioinformatics (1)

35. Give a protein structure or fragment Find protein structures in the database that are similar to it A Variety of Possible Kinds of Database Queries Can Arise in Bioinformatics (2)

36. Give a sequence of a protein of unknown structure Find structures in the database that adopt similar three- dimensional structures A Variety of Possible Kinds of Database Queries Can Arise in Bioinformatics (3)

37. For if two protein have sufficiently similar sequences They will have similar structure

38. A Variety of Possible Kinds of Database Queries Can Arise in Bioinformatics (4) Give a protein structure Find sequences in the data bank that correspond to similar structures

39. A Variety of Possible Kinds of Database Queries Can Arise in Bioinformatics  (1) and (2) are solved problems  (3) and (4) are active fields of research

40. Curation, Annotation and Quality Control  Older data were limited by older techniques Amino acid sequences of protein used to be determined by peptide sequencing. Now, almost al are translated from DNA sequences.

41. Curation, Annotation and Quality Control  Distributed error-correction and annotation  Dynamic error-correction and annotation