Chapter 1A: Introduction to Bioinformatics Can Yang Department of Mathematics Hong Kong Baptist University
Fall, 2014
C. Yang (HKBU)
Chapter 1: Introduction to Bioinformatics
Fall, 2014
1 / 31
Outline
1
Introduction
2
Examples in real life
3
A quick trip to Bio-science
4
Big Data in genomics
C. Yang (HKBU)
Chapter 1: Introduction to Bioinformatics
Fall, 2014
2 / 31
Outline
1
Introduction
2
Examples in real life
3
A quick trip to Bio-science
4
Big Data in genomics
C. Yang (HKBU)
Chapter 1: Introduction to Bioinformatics
Fall, 2014
3 / 31
The century of Bio-science
Cancer immunotherapy Genetic Microsurgery for the Masses Human Cloning at Last Cosmic Particle Accelerators Identified To Sleep, Perchance to Clean In Vaccine Design, Looks Do Matter CLARITY Makes It Perfectly Clear Dishing Up Mini-Organs Newcomer Juices Up the Race to Harness Sunlight Your Microbes, Your Health
C. Yang (HKBU)
Figure 1: Breakthrough of the Year 2013.
Chapter 1: Introduction to Bioinformatics
Fall, 2014
4 / 31
What is Bioinformatics?
Bioinformatics (http://en.wikipedia.org/wiki/Bioinformatics) Bioinformatics is an interdisciplinary scientific field that develops methods for storing, retrieving, organizing and analyzing biological data. Bioinformatics uses many areas of computer science, statistics, mathematics and engineering to process biological data.
C. Yang (HKBU)
Chapter 1: Introduction to Bioinformatics
Fall, 2014
5 / 31
Outline
1
Introduction
2
Examples in real life
3
A quick trip to Bio-science
4
Big Data in genomics
C. Yang (HKBU)
Chapter 1: Introduction to Bioinformatics
Fall, 2014
6 / 31
Example: Jolie’s Medical Choice
Figure 2: Jolie carries the BRCA1 gene, which sharply increases her risk of developing breast cancer and ovarian cancer. She was estimated to have an 87 percent risk of breast cancer and a 50 percent risk of ovarian cancer. C. Yang (HKBU)
Chapter 1: Introduction to Bioinformatics
Fall, 2014
7 / 31
Example: Are Warren and Jimmy Buffett Related? It’s no surprise that Warren and Jimmy Buffett have been long-time friends and fans of one another. Warren Buffett, chairman and chief executive of the investment fund Berkshire Hathaway. Jimmy Buffett, lead singer of the Coral Reefer Band, have a lot in common. As Fortune’s 1999 article points out, both men “play stringed instruments, stick to their guns, and are filthy rich.”
Figure 3: Warren and Jimmy Buffett. C. Yang (HKBU)
Chapter 1: Introduction to Bioinformatics
Fall, 2014
8 / 31
Example: Speed gene Scientists have discovered a variation in a gene ACTN3 that may affect whether a person will make it to the top in sports like sprinting and weightlifting that require quick bursts of powerful force. The ACTN3 gene encodes instructions for making a specific muscle protein. Researchers have found that some people have a non-working version of the gene that prevents it from making the muscle protein. More than a billion people worldwide have two copies of this variation in their DNA, causing their muscle cells to completely lack the protein. Several studies have found that Olympic-level power athletes always have at least one working copy of the ACTN3 gene. Lucia et al. Citius and longius (faster and longer) with no alpha-actinin-3 in skeletal muscles? Br J Sports Med., 41(9): 616-7., 2007.
C. Yang (HKBU)
Chapter 1: Introduction to Bioinformatics
Fall, 2014
9 / 31
Example: Human height and genes
Figure 4: Heritability: Sir Francis Galton’s (1889) data showing the relationship between offspring height (928 individuals) as a function of mean parent height (205 sets of parents). http://en.wikipedia.org/wiki/Heritability C. Yang (HKBU)
Chapter 1: Introduction to Bioinformatics
Fall, 2014
10 / 31
The Story of Muggsy Bogues When Tyrone “Muggsy” Bogues was growing up, no one expected him to be an NBA star. At only 5’ 3”, Muggsy was short, putting him at a serious disadvantage in a league where the average height is 6’ 7”. But he ignored the naysayers, and went on to have a successful basketball career despite the odds stacked against him. Genetics isn’t necessarily destiny. The story of Muggsy Bogues is a clear example of why genes alone cannot predict a person’s effectiveness or success in a certain activity. Muggsy Bogues used his strengths quickness, speed, and explosiveness - to his advantage.
C. Yang (HKBU)
Chapter 1: Introduction to Bioinformatics
Fall, 2014
11 / 31
Example: Genes mirror geography PC1 PC2
C. Yang (HKBU)
Chapter 1: Introduction to Bioinformatics
Fall, 2014
12 / 31
Outline
1
Introduction
2
Examples in real life
3
A quick trip to Bio-science
4
Big Data in genomics
C. Yang (HKBU)
Chapter 1: Introduction to Bioinformatics
Fall, 2014
13 / 31
Nobel Price, 1962: The double helix structure of DNA
Figure 5: Discovery of the the double helix structure of DNA C. Yang (HKBU)
Chapter 1: Introduction to Bioinformatics
Fall, 2014
14 / 31
DNA-RNA-Protein
Deoxyribonucleic acid (DNA) carries the genetic information of a cell and consists of thousands of genes. Each gene serves as a recipe on how to build a protein molecule. Proteins perform important tasks for the cell functions or serve as building blocks. The flow of information from the genes determines the protein composition and thereby the functions of the cell.
C. Yang (HKBU)
Chapter 1: Introduction to Bioinformatics
Fall, 2014
15 / 31
DNA-RNA-Protein The DNA is situated in the nucleus, organized into chromosomes. Every cell must contain the genetic information and the DNA is therefore duplicated before a cell divides (replication) When proteins are needed, the corresponding genes are transcribed into RNA (transcription). The RNA is first processed so that non-coding parts are removed (processing) and is then transported out of the nucleus (transport). Outside the nucleus, the proteins are built based upon the code in the RNA (translation).
C. Yang (HKBU)
Chapter 1: Introduction to Bioinformatics
Fall, 2014
16 / 31
Chromosomes Chromosomes are inherited from our parents. One chromosome from each of 23 pairs came from each of our parents. The two chromosomes of a pair (except for the sex chromosomes) contain the same genes, but the genes have small differences.
Figure 6: 23andme. https://www.23andme.com/gen101/origins/ C. Yang (HKBU)
Chapter 1: Introduction to Bioinformatics
Fall, 2014
17 / 31
Chromatin Structures
Figure 7: he major structures in DNA compaction; DNA, the nucleosome, the 10nm “beads-on-a-string” fibre, the 30nm fibre and the metaphase chromosome. http://en.wikipedia.org/wiki/Chromosome
C. Yang (HKBU)
Chapter 1: Introduction to Bioinformatics
Fall, 2014
18 / 31
Single Nucleotide Polymorphism (SNP)
Figure 8: DNA molecule 1 differs from DNA molecule 2 at a single base-pair location (a C/T polymorphism). http://en.wikipedia.org/wiki/Single-nucleotide_polymorphism C. Yang (HKBU)
Chapter 1: Introduction to Bioinformatics
Fall, 2014
19 / 31
Gene expression
Figure 9: Genes are expressed by being transcribed into RNA, and this transcript may then be translated into protein. http://en.wikipedia.org/wiki/Gene_expression
C. Yang (HKBU)
Chapter 1: Introduction to Bioinformatics
Fall, 2014
20 / 31
Outline
1
Introduction
2
Examples in real life
3
A quick trip to Bio-science
4
Big Data in genomics
C. Yang (HKBU)
Chapter 1: Introduction to Bioinformatics
Fall, 2014
21 / 31
Example: Aging
Figure 10: President Obama - One Year Into Office. When votes are counted and a president is selected they come in with hair color and leave with none to barely any color at all. Their faces began to show stress and aging as well just within a short term.
C. Yang (HKBU)
Chapter 1: Introduction to Bioinformatics
Fall, 2014
22 / 31
Telomeres
Figure 11: Elizabeth Blackburn, Carol Greider, and Jack Szostak were awarded the 2009 Nobel Prize in Physiology or Medicine for the discovery of how chromosomes are protected by telomeres and the enzyme telomerase. C. Yang (HKBU)
Chapter 1: Introduction to Bioinformatics
Fall, 2014
23 / 31
Telomere length and aging
Figure 12: Relation between age and telomere length (measured by the mean length of the terminal restriction fragments (TRF) in white blood cells) of men (a) and women (b). For men, r = −0.45; for women, r = −0.48. Athanase Benetos, et al. Telomere Length as an Indicator of Biological Aging. Hypertension, 37: 381-385, 2001. C. Yang (HKBU)
Chapter 1: Introduction to Bioinformatics
Fall, 2014
24 / 31
Telomere length and aging
For the cell, having a long telomere can be compared to having a full tank of gas in your automobile; having a short telomere is like running on empty. Each time a cell divides, its telomeres become a little shorter until the cells simply can no longer divide (e.g., it runs out of fuel).
Molecular Clock The telomere length could be considered as a molecular clock. Is there a better one?
C. Yang (HKBU)
Chapter 1: Introduction to Bioinformatics
Fall, 2014
25 / 31
The Bio-Clock: Synchronization of all tissues
C. Yang (HKBU)
Chapter 1: Introduction to Bioinformatics
Fall, 2014
26 / 31
DNA methylation age of human tissues and cell types
BigData The predictor was developed using 8,000 samples from 82 Illumina DNA methylation array datasets, encompassing 51 healthy tissues and cell types. Finally, 353 CpG sites together form an aging clock. The correlation between the predicted age and real age r = 0.96. Average error = 3.6 years.
C. Yang (HKBU)
Chapter 1: Introduction to Bioinformatics
Fall, 2014
27 / 31
DNA methylation age of human tissues and cell types
C. Yang (HKBU)
Chapter 1: Introduction to Bioinformatics
Fall, 2014
28 / 31
Big Data in Cancer genomics
Figure 13: The Cancer Genome Atlas (TCGA) Pan-Cancer analysis project, Nature Genetics, 45, 1113-1120, 2013. C. Yang (HKBU)
Chapter 1: Introduction to Bioinformatics
Fall, 2014
29 / 31
Call for data analysis paper
C. Yang (HKBU)
Chapter 1: Introduction to Bioinformatics
Fall, 2014
30 / 31
Quote
Science seldom proceeds in the straightforward logical manner imagined by outsiders. Indeed, its steps forward (and sometimes backward) are often very human events in which personalities and cultural traditions play major roles. – James Watson
C. Yang (HKBU)
Chapter 1: Introduction to Bioinformatics
Fall, 2014
31 / 31
