A Whirlwind Tour of Bioinformatics

1. A Whirlwind Tour of Bioinformatics Kun-Mao Chao (趙坤茂) National Taiwan University http://www.csie.ntu.edu.tw/~kmchao/

2. The Best? The Cheapest? The Best Entrance The Cheapest

3. Bio-X? X-Informatics? Bio-X Bioinformatics X-Informatics Source: NIH, Bioinformatics Journal, NPS

4. Interdisciplinary Pioneers Archimedes of Syracuse Isaac Newton Leonardo da Vinci Source: Wikipedia

5. Amphibia, Triphibia Source: Wikipedia, xplanes

6. My Journey

7. Band Alignment(Joint work with W. Pearson and W. Miller, 1992) Seq. 1 Seq. 2

8. Alignment in an Arbitrary Region(Joint work with R. C. Hardison and W. Miller, 1993)

9. Aligning Very Similar Sequences(Joint work with J. Zhang, J. Ostell and W. Miller, 1997)

10. Generalized Global Alignment(Joint work with X. Huang, 2003)

11. Tag SNPs & Haplotype Inference(Joint work with Y.-T. Huang et al., 2006) Yao-Ting Huang Kui Zhang Ting Chen Chia-Jung Chang Kun-Mao Chao Ting’s talk (9/26/2017): Large-Scale Metagenomic Sequence Clustering and Inference of Environment-Microbe and Microbe-Microbe Associations.

12. Sequence Comparison: Theory and Methods (Joint work with L. Zhang, 2009)

13. Bioinformatics for BiologistsEdited by Pavel Pevzner and Ron Shamir Cambridge University Press, 2011

14. Bioinformatics for BiologistsEdited by Pavel Pevzner and Ron Shamir

15. Bioinformatics for BiologistsEdited by Pavel Pevzner and Ron Shamir

16. New Methods for Analyzing Clinical Data • A Fault-tolerant Method for HLA Typing with PacBio Data[Chang et al., BMC Bioinformatics, 2014] • A fault-tolerant method based on Bayes’ theorem • Applied to simulated dataand achieving high prediction accuracy • Optimal Duration of Anti-tuberculosis Treatment in Diabetic Patients[Lee et al., CHEST, 2015] • Higher recurrence rate in DM • Reduced by treatment supervision • Reduced by extending treatment for another three months

17. SMART • SMART (Statistical Metabolomics Analysis - an RTool)[Liang et al., Analytical Chemistry, 2016] • with a user-friendly interface was developed in R and R-GUI (Graphical User Interface) under the Windows and Mac operating system.

18. Co-circulating Influenza Strains Competition

19. A Brief Introduction

20. Central Dogma of Molecular Biology Source: http://www.ncbi.nlm.nih.gov

21. From Genes to Proteins Source: http://www.ornl.gov

22. A Brief History of Genetics • 1859 Charles Darwin published “The Origin of Species.” • by Means of Natural Selection, or the Preservation of Favoured Races in the Struggle for Life • 1865 Genes are particular factors. [Gregor Mendel]

23. A Brief History of Genetics (cont’d) • 1869 Discovery of nucleic acid [Friedrich Miescher] • 1903 Chromosomes are hereditary units. [Walter Sutton] • 1910 Genes lie on chromosomes. [Thomas Hunt Morgan] • 1913 Chromosomes are linear arrays of genes. [Alfred Sturtevant] • 1931 Recombination occurs by crossing over. [Harriet Creighton and Barbara McClintock] • 1944 DNA is the genetic material. [Oswald Avery, Colin McLeod and Maclyn McCarty] • 1953 DNA is a double helix. [James Watson and Francis Crick]

24. Double Helix Source: http://www.nature.com

25. A Brief History of Genetics (cont’d) • 1961-1967 Genetic code is triplet. [Marshall Nirenberg, Har Gobind Khorana, Sydney Brenner & Francis Crick]

26. A Brief History of Genetics (cont’d) • 1977 DNA was sequenced for the first time. [Fred Sanger, Walter Gilbert, and Allan Maxam] • 21th Century: Many genomes completely sequenced

27. Multiple Nobel Laureates

28. Marie Skłodowska Curie

29. Milestones of Bioinformatics • 1962 Pauling's theory of molecular evolution • 1965 Margaret Dayhoff's Atlas of Protein Sequences • 1970 Needleman-Wunsch algorithm • 1977 DNA sequencing and software to analyze it (Staden) • 1981 Smith-Waterman algorithm developed • 1981 The concept of a sequence motif (Doolittle) • 1982 GenBank Release 3 made public • 1982 Phage lambda genome sequenced

30. Milestones of Bioinformatics (cont’d) • 1983 Sequence database searching algorithm (Wilbur-Lipman) • 1985 FASTP/FASTN: fast sequence similarity searching • 1988 National Center for Biotechnology Information (NCBI) created at NIH/NLM • 1990 BLAST: fast sequence similarity searching • 1991 EST: expressed sequence tag sequencing • 1993 Sanger Centre, Hinxton, UK • 1994 EMBL European Bioinformatics Institute, Hinxton, UK

31. Milestones of Bioinformatics (cont’d) • 1995 First bacterial genomes completely sequenced • 1996 Yeast genome completely sequenced • 1997 PSI-BLAST • 1998 Worm (multicellular) genome completely sequenced • 1999 Fly genome completely sequenced

32. Milestones of Bioinformatics (cont’d) • Human Genome Project (1990-2003) • Mouse 2002 • Rat 2004 • Chimpanzee 2005 • Completed Genomes

33. Chimpanzee Genome

34. The Primate Family Tree Source: Nature

35. Topics • Sequencing and genotyping technologies • Molecular sequence analysis • Recognition of genes and regulatory elements • Comparative genomics • Gene expression • Molecular structural biology • Biological networks • Systems biology • Computational proteomics • Molecular evolution • Phylogenetic trees • Population genetics • Medical informatics

36. Bioinformatics Centers • National Center for Biotechnology Information (NCBI, NIH): • http://www.ncbi.nlm.nih.gov/ • European Bioinformatics Institute (EBI): • http://www.ebi.ac.uk/ • DNA Data Bank of Japan (DDBJ): • http://www.ddbj.nig.ac.jp/index-e.html • UCSC Genome Browser Home • RCSB Protein Data Bank

37. Bioinformatics Departments • Biomedical Electronics and Bioinformatics, NTU • Computational Biology and Bioinformatics, USC • Bioinformatics and Systems Biology, UCSD • The Broad Institute of MIT and Harvard • Computational and Genomic Biology, UC Berkeley • Biomedical Informatics Research, Stanford University • Comparative Genomics and Bioinformatics, Penn State • Max Planck Institute for Molecular Genetics • Bioinformatics and Computational Biology, Iowa State

38. Bioinformatics Journals • Bioinformatics • Journal of Computational Biology • Genome Research • Nature • Nucleic Acid Research • PLoS Computational Biology • Science

39. Nature & Science

40. Bioinformatics Conferences • The Annual International Conference on Research in Computational Molecular Biology (RECOMB) • The Symposium on Intelligent Systems for Molecular Biology (ISMB) • The European Conferences on Computational Biology (ECCB)

41. Books

42. Books (Cont’d) • All grading for the 100+ homework problems in the book is automatically done through the popular online bioinformatics education website Rosalind. All problems represent programming challenges with randomized input given to students.

43. Bioinformatics Community • The International Society for Computational Biology (ISCB) • Senior Scientist Accomplishment Award

44. Ten Steps to Success in Bioinformatics by Webb Miller • Become a biologist. • Value your number of citations above your number of publications. • Collaborate, and do it with great collaborators. • Do not expect a warm welcome from everyone. • Be a good collaborator. • Distribute and maintain software and/or run web servers that you personally continue to use.

45. 10 Steps to Success in Bioinformaticsby Webb Miller • Alternate between working on specific datasets and writing general-purpose software. • Write some of your own software. • Don't give up. • Be excited about your work.

46. “Discovery is to see what everyone else has seen, but think what no one else has thought.” Albert Szent-Györgyi(The Nobel Prize in Physiology or Medicine, 1937 ) “By inventing elegant software tools, we can help biologists see and think.” “Invention  Discovery” Kun-Mao Chao