CS284A Introduction to Computational
Biology and Bioinformatics
Xiaohui S. Xie
University of California, Irvine
Todays Goals
Course information
Challenges in computational biology
Introduction to molecular biology
Course Information
Lecture: MW 3:30-4:50pm in ICS243
Grading
30% Homework
20% Midterm exam
50% Final project
Exams
In-class midterm, no final exams
Course Prerequisites:
Programming skill (Perl/Python, Matlab/R)
Statistics and Calculus
Course Goals
Introduction to computational biology
Fundamental problems in computational biology
Statistical, algorithmic and machine learning techniques
Directions for future research in the field
Final project:
Propose an innovative project
Design novel or implement previous algorithms to carry out the
project
Write-up goals, approach and findings in a conference format
Present your project to your peers in a conference setting
References
Recommended Textbooks:
R. Durbin, S. Eddy, A. Krogh and G. Mitchison. Biological
Sequence Analysis
P. Baldi and S. Brunak. Bioinformatics: the Machine Learning
Approach
Course Website:
http://www.ics.uci.edu/~xhx/courses/CS284A/
Why computational biology?
Computational biology/Bioinformatics is the application of
computational tools and techniques to biology (mostly
molecular biology).
Lots of data
Pattern finding, rule discovery
Allowing analytic and predictive methodologies that support
and enhance lab work
Informatics infrastructure (data storage, retrieval)
Data visualization
Lift itself is a computer!
Four Aspects
Biology
Whats the problem?
Algorithm
How to solve the problem efficiently?
Learning
How to model biology systems and learn from observed
data?
Statistics
How to differentiate true phenomena from artifacts?
Topics to be covered
DNA/RNA/Protein sequence analysis
Pattern finding (motif discovery)
Sequence alignment (Smith-Waterman, BLAST)
Models of sequences (HMM)
Gene discovery
RNA folding
Algorithms for large-scale data analysis
Clustering algorithms (Hierarchical clustering, K-means)
Inference of networks (Regression, Bayesian networks)
Systems biology
Evolutionary models
Phylogenetic trees
Comparative Genomics
Protein world (if time allows)
Secondary & tertiary structure prediction
Introduction to Molecular Biology
and Genomics
Slides from Mark Cravens
Deoxyribonucleic acid (DNA)
can be thought of as the blueprint for an organism
composed of small molecules called nucleotides
four different nucleotides distinguished by the four bases:
adenine (A), cytosine (C), guanine (G) and thymine (T)
is a polymer: large molecule consisting of similar units (nucleotides in this case)
DNA is digital information
a single strand of DNA can be thought of as a string composed of the four
letters: A, C, G, T
AGCGGTTAAGGCTGATATGCGCTTTAA
TCGCCAATTCCGACTATACGCGAAATT
The Double Helix
DNA molecules usually consist of two strands arranged in the famous
double helix
Watson-Crick Base Pairs
A bonds to T
C bonds to G
3-5
strand
5-3 strand
Four nucleotides
Chromosomes
DNA is packaged into individual chromosomes (along with
proteins)
prokaryotes (single-celled organisms lacking nuclei) have a
single circular chromosome
eukaryotes (organisms with nuclei) have a species-specific
number of linear chromosomes
DNA + associated chromosomal proteins = chromatin
DNA organization
Human Chromosomes
Karyogram of a human male
Genomes
The term genome refers to the complete complement of
DNA for a given species
The human genome consists of 46 chromosomes
Male: 22 pairs of autosomes + XY
Female: 22 pairs of autosomes + XX
Every cell (except sex cells and mature red blood cells)
contains the complete genome of an organism
Human Genome (Male)
22 pairs of autosomes + sex chromosomes (XY)
10
Human Genome (Female)
22 pairs of autosomes + sex chromosomes (XX)
Proteins
Proteins are molecules composed of one or more
polypeptides
A polypeptide is a polymer composed of amino
acids
Cells build their proteins from 20 different amino
acids
A polypeptide can be thought of as a string
composed from a 20-character alphabet
11
Protein Functions
structural support
storage of amino acids
transport of other substances
coordination of an organisms activities
response of cell to chemical stimuli
movement
protection against disease
selective acceleration of chemical reactions
Amino Acids
12
Amino Acid Sequence of
Hexokinase
Protein Structure
Proteins are
poly-peptides
of 70-3000
amino-acids
This structure
is (mostly)
determined by
the sequence
of amino-acids
that make up
the protein
13
Space-Filling Model of Hexokinase
Hemoglobin
protein built from 4
polypeptides
responsible for
carrying oxygen in
red blood cells
14
Genes
Genes are the basic units of heredity
A gene is a sequence of bases that carries the
information required for constructing a particular
protein (polypeptide really)
Such a gene is said to encode a protein
The human genome comprises ~22,000 genes
Those genes encode >100,000 polypeptides
RNA genes: microRNAs and other small RNAs
The Central Dogma
15
RNA
RNA is like DNA except:
backbone is a little different
usually single stranded
the base uracil (U) is used in place of thymine (T)
A strand of RNA can be thought of as a string
composed of the four letters: A, C, G, U
Transcription
16
Transcription
RNA polymerase is the enzyme that builds an
RNA strand from a gene
RNA that is transcribed from a gene is called
messenger RNA (mRNA)
The Genetic Code
64 combinations: 20 amino acids + stop codon
17
Genetic code: DNA -> mRNA -> protein
Translation
Ribosomes are the machines that synthesize
proteins from mRNA
The grouping of codons is called the reading frame
Translation begins with the start codon
Translation ends with the stop codon
18
Codons and Reading Frames
Genes include both coding regions as well as control regions
19
RNA Splicing: pre mRNA --> mRNA
Different Life Forms Share a Common Genetic Framework
20
Comparison of genome size
Organisms
Genomes
Haemophilus
influenzae
Methannococcus
Saccharomyces
Caenorhabditis
Drosophila
Mus
Homo
jannaschii
cerevisiae
elegans
Melanogaster
musculus
sapiens
(bakers yeast)
(nematode
worm)
(fruit fly)
(laboratory
mouse)
(man)
Genome
(MB)
1.83
1.66
13
97
180
3200
3500
Number
of genes
1709
1682
6241
18,424
13,500
~30,000
~30,000
Sequenced Genomes
Science 1995 Jul 28;269(5223):496-512
Whole-genome random sequencing and assembly of Haemophilus influenzae Rd. Fleischmann RD et al.
Science 1996 Aug 23;273(5278):1058-73
Complete genome sequence of the methanogenic archaeon, Methanococcus jannaschii. Bult CJ et al.
Science 1996 Oct 25;274(5287):546, 563-7
Life with 6000 genes. Goffeau A et al.
Science 1998 Dec 11;282(5396):2012-8; errata in Science 1999 Jan; 283(5398):35 and 1999 Mar 26;283(5410):2103
and 1999 Sep 3;285(5433):1493
Genome sequence of the nematode C. elegans: a platform for investigating biology. The C. elegans Sequencing
Consortium.
Science 2000 Mar 24;287(5461):2185-95
The genome sequence of Drosophila melanogaster. Adams MD et al.
Feb, 2001 Human Genome in both Nature and Science
Science 2002 Aug 23;297: 1301-1310
Whole-genome shotgun assembly and analysis of the genome of Fugu rubripes Aparicio S. et al.
Nature 2002 Dec 5; 420:520-62
Initial sequencing and comparative analysis of the mouse genome. Waterston et al.
Nature 2004 Apr 5; 428:493-512 Genome sequence of the Brown Norway rat yields insights into mammalian
evolution. Gibbs et al.
Nature 2005 Sep 1; 437:69-87 Initial sequence of the chimpanzee genome and comparison with the human genome
21
Genes
The DNA strings include:
Coding regions (genes)
E. coli has ~4,000 genes
Yeast has ~6,000 genes
C. Elegans has ~18,000 genes
Humans have ~30,000 genes
Control regions
These typically are adjacent to the genes
They determine when a gene should be expressed
Junk DNA (better to be called DNA with unknown function)
98% of the human genome unknown
Human
Genome
~3Gb
Coding exons
1.5%
Other known
function
0.2%
Others
48%
Repeats
50%
22
The Cell
All cells of an organism contain the same DNA content
(and the same genes) yet there is a variety of cell types.
Example: Tissues in Stomach
How is this variety encoded and expressed ?
23
Readout from the genome
24
