Introduction to BioinformaticsIntroduction to Bioinformatics

What is BioinformaticsWhat is Bioinformatics

Easy AnswerUsing computers to solve molecular biology

problems; Intersection of molecular biology and computer science

Hard AnswerComputational techniques (e.g. algorithms, artificial

intelligence, databases) for management and analysis of biological data and knowledge

BioinformaticsBioinformatics

Bioinformatics = Biology + Information

Biology is becoming an information science

Computation methods are necessary to analyze the massive amount of information that coming out of the genome projects

Bioinformatics is Another Bioinformatics is Another Revolution in BiologyRevolution in Biology

Three concepts, which remain Three concepts, which remain central to Bioinformaticscentral to Bioinformatics

Data representation

A complex, dynamic, three-dimensional molecule a simple string of characters

Three concepts, which remain Three concepts, which remain central to Bioinformaticscentral to Bioinformatics

The concept of similarity– Evolution has operated on every sequence– In biomolecular sequences (DNA, RNA or amino acid

sequences). High sequence similarity usually implies significant functional or structural similarity.

– The opposite is not true– Algorithms for comparing sequences and finding

similar regions are at the heart of bioinformatics

Three concepts, which remain Three concepts, which remain central to Bioinformaticscentral to Bioinformatics

Bioinformatics is not a theoretical science; it is driven by the data, which in turn is driven by the needs of biology.

Sequences

Microarray technologies

…

GenBank GrowthGenBank Growth

Moore’s LawMoore’s Law

What do you need to know?What do you need to know?

It all depends on your background

Are you a …? Biologist with some computer knowledge, or Computer scientist with some biology

background

Few do both well

BackgroundBackground

Biology for Computer Scientists

Computer Science for Biologists

Biological Information FlowBiological Information FlowGenome Introns/Exons

Gene Sequence

Protein Sequence

Protein Functions

Protein Structure

Cellular Pathways

Bioinformatics attempts to model this pathway

Living ThingsLiving Things

Entropy (the tendency to disorder) always increase

Living organisms have low entropy compared with things like soil

They are relatively orderly…

The most critical task is to maintain the distinction between inside and outside

Living ThingsLiving Things

In order to maintain low entropy, living organisms must expend energy to keep things orderly.

They figured out how to do this 4 billion years ago

The functions of life, therefore, are meant to facilitate the acquisition and orderly expenditure of energy

Living ThingsLiving Things

The compartments with low entropy are separated from “the world.”

Cells are the smallest unit of such compartments.

Bacteria are single-cell organismsHumans are multi-cell organisms

The “living things” have the The “living things” have the following tasks:following tasks:

Gather energy from environment Use energy to maintain inside/outside distinction Use extra energy to reproduce Develop strategies for being successful and

efficient at the above tasks– Develop ways to move around– Develop signal transduction capabilities (e.g. vision)– Develop methods for efficient energy capture (e.g.

digestion)– Develop ways to reproduce effectively

How to accomplish…?How to accomplish…?

Living compartments on earth have developed three basic technologies– Ability to separate inside from outside (lipids)– Ability to build three-dimensional molecules

that assist in the critical functions of life (Protein, RNA)

– Ability to compress the information about how (and when) to build these molecules in linear code (DNA)

Bioinformatics Schematic of a Bioinformatics Schematic of a CellCell

LipidsLipids

Made of hydrophilic (water loving) molecular fragment connected to hydrophobic fragments

Spontaneously form sheets (lipid membranes) in which all the hydrophilic ends align on the outside, and hydrophobic ends align on the inside

Creates a very stable separation, not easy to pass through except for water and a few other small atoms/molecules

What is Nucleotide?What is Nucleotide? Pentose, base, phosphate group

Pentose: RNA and DNAPentose: RNA and DNA

BaseBase

Adenine (A), Cytosine (C), Guanine (G), Thymine (T),

Uracil (U).

Nucleic Acid ChainNucleic Acid Chain

Condensation reaction Orientation From 5’ to 3’ In DNA or RNA, a nucleic

acid chain is called “Strand”– DNA: double-stranded– RNA: a single strand

The number of bases– Base pair (bp) in DNA

DNA StructureDNA Structure

DNA StructureDNA Structure

DNA StructureDNA Structure

RNA Structure and FunctionRNA Structure and Function

• The major role of RNA is to participate in protein synthesis

•Messenger RNA (mRNA)

•Transfer RNA (tRNA)

•Ribosomal RNA (rRNA)

mRNAmRNA

The Genetic CodeThe Genetic Code

What is gene?What is gene?

A gene includes the entire nucleic acid sequence necessary for the expression of its product.

Such sequence may be divided into– Regulatory region– Transcriptional region: exons and introns

Exons encode a peptide or functional RNA Introns will be removed after transcription

GeneGene

GenomeGenome

The total genetic information of an organism.

For most organisms, it is the complete DNA sequence

For RNA viruses, the genome is the complete RNA sequence

Genes and ControlGenes and Control

Human genome has 3,000,000,000 bps divided into 23 liner segments (chromosome)

A gene has an average 1340 DNA bps, thus specifying a protein of about ? (how many) amino acids

Humans have about 35,000 genes = 40,000,000 DNA bps = 3% of total DNA in genome

Human have another 2,960,000,000 bps for control information. (e.g. when, where, how long, etc…)

Gene ExpressionGene Expression

An organism may contain many types of cells, each with distinct shape and function

However, they all have the same genome

The genes in a genome do not have any effect on cellular functions until they are “expressed”

Different types of cells express different sets of genes, thereby exhibiting various shapes and functions

Gene ExpressionGene Expression

The production of a protein or a functional RNA from its gene

Several steps are required– Transcription– RNA processing– Nuclear transport– Protein synthesis

Gene ExpressionGene Expression

Central DogmaCentral Dogma

DNA RNA Protein

Next …Next …

Protein Structure and FunctionProtein Structure and Function

An Amino AcidAn Amino Acid

An amino acid is defined as the molecule containing an amino group (NH2), a carboxyl group (COOH) and an R group.

R-CH(NH2)-COOH

The R group differs among various amino acids. In a protein, the R group is also call a sidechain.

An Amino AcidAn Amino Acid

The Twenty Amino Acids of The Twenty Amino Acids of ProteinsProteins

The Twenty Amino Acids of The Twenty Amino Acids of ProteinsProteins

ProteinProtein

Peptide ― a chain of amino acids linked together by peptide bonds.

Polypeptides ― long peptides

Oligopeptides ― short peptides (< 10 amino acids)

Protein are made up of one or more polypeptides with more than 50 amino acids

Protein StructureProtein Structure Primary Structure

– Refers to its amino acid sequence

Secondary structureSecondary structure

Regular, repeated patterns of folding of the protein backbone.

Two most common folding patterns– Alpha helix– Beta sheet

Tertiary StructureTertiary Structure

The overall folding of the entire polypeptide chain into a specific 3D shape

Quaternary StructureQuaternary Structure

Many proteins are formed more than one polypeptide chain

Describe the way in which the different subunits are packed together to form the overall structure of the protein

Hemoglobin molecule

Quaternary StructureQuaternary Structure

EvolutionEvolution

Mutation ― rare events, sometimes single base changes, sometimes larger events

Recombination ― how your genome was constructed as a mixture of your two parents

Through Natural Selection Homology (similarity): different species are

assumed to have common ancestors The genetic variation between different people is

…(surprisingly ..)

ReferencesReferences

http://www.biology.arizona.edu/biochemistry/problem_sets/large_molecules/

http://helix-web.stanford.edu/bmi214/index2004.html

http://www.web-books.com/MoBio/http://www.cs.sunysb.edu/~skiena/549/