overview of i519 & introduction to bioinformatics
TRANSCRIPT
Overview of I519 & Introduction to Bioinformatics
Structure of I519 Two classes and one lab each week Python, C (a little bit R) Textbook: Understanding Bioinformatics Homework assignments (~5 in total) Grading:
– midterm exam (25%) + final exam (25%) + assignments (30%) + class project (15%) + attendance (5%)
Course webpage: http://darwin.informatics.indiana.edu/col/courses/I519-12/
What’s Bioinformatics "Bioinformatics is the field of science in which biology,
computer science, and information technology merge into a single discipline. There are three important sub-disciplines within bioinformatics: the development of new algorithms and statistics with which to assess relationships among members of large data sets; the analysis and interpretation of various types of data including nucleotide and amino acid sequences, protein domains, and protein structures; and the development and implementation of tools that enable efficient access and management of different types of information.” (NCBI)
"I do not think all biological computing is bioinformatics, e.g. mathematical modelling is not bioinformatics, even when connected with biology-related problems. In my opinion, bioinformatics has to do with management and the subsequent use of biological information, particular genetic information.” (Durbin)
What’s bioinformatics
Bioinformatics vs Computational Biology
Almost interchangeable Computational biology may be broader
– Computational biology is an interdisciplinary field that applies the techniques of computer science, applied mathematics and statistics to address biological problems (wikipedia)
– Includes bioinformatics
What’s bioinformatics
Impacts of Bioinformatics
On biological sciences (and medical sciences)– Large scale experimental techniques – Information growth
On computational sciences– Biological has become a large source for new
algorithmic and statistical problems!
What’s bioinformatics
Related Fields Proteomics/genomics (metagenomics)/
comparative genomics/structural genomics Chemical informatics Health informatics/Biomedical informatics Complex systems Systems biology Biophysics Mathematical biology
– tackles biological problems using methods that need not be numerical and need not be implemented in software or hardware
What’s bioinformatics
Bioinformatics Problems/Applications
Figure from “Bioinformatics dummies”
What’s bioinformatics
Biology Primer
Figure 1-1 Molecular Biology of the Cell
Multicullar organisms
Eggs
Cell divisions
Underlying the diversity of life is a striking unity: DNA is universal genetic language; Cells are the basic units of structure and function
Biology primer
Cells are the Basic Unit of Life Cell Theory
– All organisms are made up of cells
– The cell is the basic living unit of organization for all organisms
– All cells come from pre-existing cells by division
– Cells contains hereditary information which is passed from cell to cell during cell division.
– All cells are basically the same in chemical composition
– All energy flow (metabolism & biochemistry) of life occurs within cells
Organisms can be of single cells or multiple cells (multicellular organisms)− Most living organisms are single cells (e.g., E.coli, Yeast)
− Multicellular organisms (e.g., human has more than 1013 cells. Have no idea about this number? World population as of July 2008 is 6.684 billion, (1 billion = 109)
Biology primer
Animal cell structurehttp://hyperphysics.phy-astr.gsu.edu/hbase/biology/imgbio/cellhlabel.gif
Cell Structures
Prokaryotic cell structurehttp://micro.magnet.fsu.edu/cells/procaryotes/images/procaryote.jpg
Biology primer
Scale Down to the Atomic Level
Figure 9-1 Molecular Biology of the Cell Figure 9-2
Cell
Biology primer
The Central Dogma
DNA RNA Protein
RNA virus
retrovirus
TranslationTranscription
The flow of genetic information in cells is from DNA to RNA to protein. All cells, from bacteria to humans, express their genetic information in this way—a principle so fundamental that it is termed the central dogma of molecular biology.
Biology primer
DNA and Replication
Figure 1-2 Molecular Biology of the Cell, Fifth Edition
Biology primer
From DNA (to RNA) to Protein
Biology primer
The Genetic Code
Biology primer
Genome Definition
– Genome of an organism is its whole hereditary information and is encoded in the form of DNA (or, for some viruses, RNA)
– Chromosome: structure composed of a long DNA and associated proteins; human has 46 chromosomes
DNA sequences can be determined by various sequencing techniques
Sequence first. Ask questions later– Cell. 2002 Oct 4;111(1):13-6
Biology primer
Characteristic Archaea Bacteria Eukaryotes
Predominately multicellular No No Yes
DNA structure circular circular linear
Cytoplasma is compartmentalized
No No Yes
Introns are present in most genes
No No Yes
Photosynthesis with chlorophyll
No Yes Yes
Histone proteins present in cell
Yes No Yes
Three (Super)Kingdoms
Biology primer
Organisms at Pivotal Positions in the Tree of Life
E.coli: 1997
Cell. 2002 Oct 4;111(1):13-6
Fly: 2000
Worm: 1998
Biology primer
Model Organisms
A model organism is a species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the organism model will provide insight into the workings of other organisms.
Genetic models (with short generation times, such as the fruit fly and nematode worm), experimental models, and genomic models, with a pivotal position in the tree of life
Biology primer
Escherichia coli (E. coli)
A common gut bacterium, is the most widely-used organism in molecular genetics.
Some strains of E. coli are capable of causing disease under certain conditions
Different strains of E. coli have been extensively studied
Whole genome of several E. coli strains was sequenced (e.g., K-12, O157:H7, HS)
Biology primer
The Genome of E. coli K-12
Figure 1-29 Molecular Biology of the Cell, Fifth Edition (© Garland Science 2008)
Circular DNA: a single, closed loop
Protein-coding genes
RNA genes
The whole genome was sequenced in 1997Total 4,639,221 bp.
Biology primer
Caenorhabditis elegans
C. elegans is a eukaryote (nematodes, or round worms)
Has small genome (~97megabases) (whole genome sequencing, 1998)
C. elegans is easy to maintain in the laboratory (in petri dishes) and has a fast and convenient life cycle. – the life span is 2-3 weeks.
– tiny (1 mm in length) and transparent organism and the developmental pattern of all 959 of its somatic cells has been traced.
• somatic cell: any cell of a plant or animal other than cells of the germ line (from Greek soma, body)
Biology primer
Caenorhabditis elegans (Cont.) Discovery of the mechanism of
RNA interference in C. elegans (1998)– Andrew Fire and Craig C. Mello shared the
Nobel Prize in Physiology or Medicine in 2006
– Silencing was triggered efficiently by injected dsRNA, but weakly or not at all by sense or antisense single-stranded RNAs
Biology primer
Drosophila melanogaster (fruit fly) It has been used as a model organism for over
100 years, widely used to study genetic and development biology– Small and has a simple diet.
– Short life cycle: taking about two weeks
– Have large polytene chromosomes, whose barcode patterns of light and dark bands allow genes to be mapped accurately
It was chosen in 1990 as one of the model organisms to be studied under the auspices of the federally funded Human Genome Project
Whole genome sequenced in 2000 >10 Drosophila genomes have been sequenced FlyBase: http://flybase.org/
Biology primer
Species Classification
Classification is arrangement of organisms into orderly groups based on their similarities
Also known as taxonomy Provide accurate and uniform naming system
Biology primer
Linnaean System of Classification Carolus Linnaeus (the “father of taxonomy”) -- the first
widely accepted hierarchical scheme, which consists today of 7 categories (kingdom, phylum, class, order, family, genus, and species) (not including domain)
Species is the most basic unit of biological classification (means “kind” in Latin)– Each species is different, and reproduces itself faithfully– Heredity is a central part of the definition of life
The Linnaean system uses two Latin name categories, genus and species, to designate each type of organism– Salmonela saintpaul (which caused the latest food-borne
disease)
– Capitalize the genus, but not the species; italicized in print
Biology primer
Homo sapiens
Domain: Eukaryotes Kingdom: Matazon (many-celled animal)
Phylum: Chordata (characterized by a notochord, nerve cord, and gill
slits)
(subphylum: Vertebrata) Class: Mammalia (warm-blooded vertebrates)
Order: Primates
Family: Hominidae
Genus: Homo
Species: Sapienshttp://www.ncbi.nlm.nih.gov/sites/entrez?db=taxonomy
King
Philip
Came
Over
For
Gooseberry
Soup
Biology primer
Gene/Protein Family A protein/gene family is a group of evolutionarily
related proteins/genes Genes/proteins of the same family typically have
similar functions (and structures for proteins) and with sequence similarity
There are far more genes/proteins than the number of families—which shows the advantage of grouping genes/proteins into different families
Biology primer
Evolution of Genes
New genes are generated from preexisting genes– Intragenic mutation (modified by changes in DNA
sequence – errors occurred in the process of DNA replication)
– Gene duplication – two copies of genes may then diverge in the course of evolution
– Segment shuffling– Horizontal transfer
Biology primer
Analysis of Gene/Protein Families – Key Problems in Bioinformatics
Homolog detection Alignment (the residual-level mapping among
homologous genes/proteins) Application of the alignments
– Detect the conserved residues – functional sites– Prediction of protein structures– Motif finding (cis-elements)
Phylogeny Function annotation
None of these problems have been solved!
More on what’s bioinformatics
Is Protein A Related/Similar to Protein B?
Sequence similarity (alignment!) Structure similarity (structural comparison) Co-expression (Microarray data analysis) Any types of correlation (operon-structure, etc)
You will see this question again and again!
More on what’s bioinformatics
Guilty by AssociationMore on what’s bioinformatics
Computational Abstractions: Biological Sequences as Strings
DNA RNA Protein Phylotype
DNA A string in a four-letter alphabet
RNA
Protein
More on what’s bioinformatics
Computational Abstractions: Networks (and Others) as Graphs
Protein-protein interaction network Protein structures presented as graphs Gene functions presented as graphs (Gene
ontology) Metabolic pathways as graphs (directed)
More on what’s bioinformatics
Large Scale Data Analysis
Genome scale– genome, proteome, transcriptome
Metagenome scale– Metagenome, metaprotome, metatranscriptome
More on what’s bioinformatics
More than Implementation Find old/new biological problems
– Remember biology has become a large source for new algorithmic and statistical problem
Formulate as a computational problem– Define inputs and outputs
– (though there are many paper work on well-defined bioinformatics problems)
Apply existing algorithms and/or tools to solving your problem
Develop new ones if necessary Implement your algorithms with appropriate
programming language(s)
More on what’s bioinformatics
Where Can I Get the Biological Data?
Sequences– NCBI genbank– Swissprot
Structures– PDB
Genomes– NCBI, IMG, GOLD– Specialized genome resources
• Ensembl: selected eukaryotic genomes.
Others– KEGG, SEED (biological pathways)
More on what’s bioinformatics
Dealing with Databases
Databases are the backbone of bioinformatics research
Flat files were the first type of database; and are still used today
Rational databases are good for searching purposes
Databases can contain data and annotations of data– Primary and derived (secondary) data
Readings Biology primer (available at the course website) Anything about Python and/or C (if you have no
programming experience at all)
What’s in the textbook?– Chapter 1 （ The Nucleic Acid World)– Chapter 2 (Protein Structure)– Chapter 3 (Dealing With Databases)