1. Impact of Formal Methods in Biology and Medicine
Debashis Sahoo
Department of Computer Science
CSE291 – H00 – Lecture 1

2. Outline Introduction History of Bioinformatics
Introduction to computing
Data collection
Experiment design
Data analysis

3. Bioinformatics Definition
Biological Data
Representation
Storage
Access
Processing
bi·o·in·for·mat·ics [bahy-oh-in-fer-mat-iks]
noun ( used with a singular verb ) the retrieval and analysis of biochemical and biological data using mathematics and computer science, as in the study of genomes.

6. Professor Donald E. Knuth
The "father" of the analysis of algorithms
He is the author of the seminal multi-volume work The Art of Computer Programming.
“It is hard for me to say confidently that, after fifty more years of explosive growth of computer science, there will still be a lot of fascinating unsolved problems at peoples' fingertips, that it won't be pretty much working on refinements of well-explored things. I can't be as confident about computer science as I can about biology. Biology easily has 500 years of exciting problems to work on, it's at that level.”

7. Historical perspective

8. History of Bioinformatics
Gergor Mendel (1866, Verhandlungen des naturforschenden Vereins Brünn)
1951 – structure for the alpha-helix and beta-sheet
Pauling and Corey (PNAS – 1951)
double helix model for DNA
Watson and Crick (Nature, 171: , 1953)
1955 – protein sequence of bovine insulin
F. Sanger.

9. History of Bioinformatics
1958 – 1990
Revolution in Computer Science and Engineering
Computer, , network, internet
1990 – BLAST
Altschul, S.F., Gish, W., Miller, W., Myers, E.W. & Lipman, D.J. (1990) "Basic local alignment search tool." J. Mol. Biol. 215:
The Haemophilus influenzea genome (1.8 Mb) is sequenced.
1993 – 2013 – Microarrays
2005 – 2013 – High-throughput sequencing

10. Introduction to computing

11. What is a computer? 1 1 1 1 Controller Turing Machine (1936) Tape1 1 1
Read/Write head
Controller
Turing Machine (1936)
Alan Turing, "On computable numbers, with an application to the Entscheidungsproblem", Proceedings of the London Mathematical Society, Series 2, 42 (1937), pp 230–265.

12. Modern Computer Main Memory Processor Disk Drives IO controller
Display
Keyboard
Mouse

13. What is a Computer Program?
Assembly Program
C Program
Executable file
Load to Memory
Run the program

14. Data collection

15. Public Databases Gene Expression Omnibus (GEO) Array Express
National Center for Biotechnology Information (NCBI)
UCSC Genome Browser
The human protein atlas
Catalogue of Somatic Mutations in Cancer – COSMIC
The Cancer Genome Atlas (TCGA)

22. https://tcga-data.nci.nih.gov/tcga/

23. Experiment design

24. To call in the statistician after the experiment is done may be no more than asking him to perform a postmortem examination : he may be able to say what the experiment died of.
- R. A. Fisher

26. Independent Samples
Statistical tests are based on the assumption that each subject was sampled independently.
Provides maximum amount of information.
Provides better estimation of the mean.

27. The Gaussian Approximation
Everybody believes in the normal approximation, the experimenters because they think it is a mathematical theorem, the mathematicians because they think it is an experimental fact.
G. Lippman (1845 – 1921)

28. Sample Size Estimation

29. Data analysis

30. Correlation

31. Hypothesis Testing Randomly select samples from the population
State the null hypothesis
Distribution of values in two different populations are the same
Perform the statistical test
T test, F test, Chi-sq test
Get P-value
Set a threshold (usually < 0.05) for significance

32. Multiple Comparisons The Bonferroni correction
P < 0.05/N (N = number of comparisons)
False Discovery Rate (FDR) – Q value
What fraction of all the discoveries are false?
Q = 10%, N = 100, smallest p-value < Q/N
Permutation based approaches