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Genomics, Proteomics, and Bioinformatics. Biology 224 Instructor: Tom Peavy August 31, 2009. What is bioinformatics?. Interface of biology and computers Analysis of genomes, genes, mRNA and proteins using computer algorithms and computer databases. What is Genomics?.

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genomics proteomics and bioinformatics

Genomics, Proteomics, and Bioinformatics

Biology 224

Instructor: Tom Peavy

August 31, 2009

slide2

What is bioinformatics?

  • Interface of biology and computers
  • Analysis of genomes, genes, mRNA and proteins using computer algorithms and computer databases
slide3

What is Genomics?

What is Proteomics?

What is the Transcriptome?

slide4

On bioinformatics

“Science is about building causal relations between natural phenomena (for instance, between a mutation in a gene and a disease). The development of instruments to increase our capacity to observe natural phenomena has, therefore, played a crucial role in the development of science - the microscope being the paradigmatic example in biology. With the human genome, the natural world takes an unprecedented turn: it is better described as a sequence of symbols. Besides high-throughput machines such as sequencers and DNA chip readers, the computer and the associated software becomes the instrument to observe it, and the discipline of bioinformatics flourishes.”

Martin Reese and Roderic Guigó, Genome Biology 2006 7(Suppl I):S1,

introducing EGASP, the Encyclopedia of DNA Elements (ENCODE) Genome Annotation Assessment Project

slide6

Themes throughout the course:

gene/protein families

  • Retinol-binding protein 4 (RBP4)
  • member of the lipocalin family
  • small, abundant carrier protein

We will study it in a variety of contexts including

  • --homologs in various species
  • --sequence alignment
  • --gene expression
  • --protein structure
  • --phylogeny
slide8

bioinformatics

medical

informatics

public health

informatics

algorithms

databases

infrastructure

Tool-users

Tool-makers

slide9

DNA

RNA

protein

phenotype

protein

sequence

databases

cDNA

ESTs

UniGene

Microarrays

genomic

DNA

databases

slide10

There are three major public DNA databases

EMBL

GenBank

DDBJ

Housed

at EBI

European

Bioinformatics

Institute

Housed

at NCBI

National

Center for

Biotechnology

Information

Housed

in Japan

slide11

Growth of GenBank

Base pairs of DNA (billions)

Sequences (millions)

1982

1986

1990

1994

1998

2002

Updated 8-12-04:

>40b base pairs

Year

slide12

Growth of GenBank + Whole Genome Shotgun

(1982-November 2008)

250

200

150

Number of sequences

in GenBank (millions)

Base pairs of DNA in GenBank (billions)

Base pairs in GenBank + WGS (billions)

100

50

0

1982

1987

1992

1997

2002

2007

slide13

Taxonomy at NCBI:

~200,000 species are represented in GenBank

11/08

http://www.ncbi.nlm.nih.gov/Taxonomy/txstat.cgi

slide14

The most sequenced organisms in GenBank

Homo sapiens 13.1 billion bases

Mus musculus8.4b

Rattus norvegicus6.1b

Bos taurus 5.2b

Zea mays 4.6b

Sus scrofa 3.6b

Danio rerio3.0b

Oryza sativa (japonica)1.5b

Strongylocentrotus purpurata 1.4b

Nicotiana tabacum 1.1b

Updated 11-6-08

GenBank release 168.0

Excluding WGS, organelles, metagenomics

slide15

Go to NCBI website

http://www.ncbi.nlm.nih.gov/

slide16

PubMed is…

  • National Library of Medicine's search service
  • 12 million citations in MEDLINE
  • links to participating online journals
  • PubMed tutorial (via “Education” on side bar)
slide17

Entrez integrates…

  • the scientific literature;
  • DNA and protein sequence databases;
  • 3D protein structure data;
  • population study data sets;
  • assemblies of complete genomes
slide18

Entrez is a search and retrieval system

that integrates NCBI databases

slide19

BLAST is…

  • Basic Local Alignment Search Tool
  • NCBI's sequence similarity search tool
  • supports analysis of DNA and protein databases
  • 80,000 searches per day
slide20

OMIM is…

  • Online Mendelian Inheritance in Man
  • catalog of human genes and genetic disorders
  • edited by Dr. Victor McKusick, others at JHU
slide21

Books is…

  • searchable resource of on-line books
slide22

TaxBrowser is…

  • browser for the major divisions of living organisms
  • (archaea, bacteria, eukaryota, viruses)
  • taxonomy information such as genetic codes
  • molecular data on extinct organisms
slide23

Structure site includes…

  • Molecular Modelling Database (MMDB)
  • biopolymer structures obtained from
  • the Protein Data Bank (PDB)
  • Cn3D (a 3D-structure viewer)
  • vector alignment search tool (VAST)
slide32

Synonymous

Substitution

Non-synonymous

Substitution

central dogma
Central Dogma
  • DNA  RNA  protein
  • sequence  structure  function  evolution
slide34

What kind of modifications

Are made to Eukaryotic mRNAs?

protein structures
Protein structures
  • X-ray crystallography and Nuclear magnetic resonance (NMR)
  • Primary structure
    • linear AA
  • Secondary structure-
    • alpha helix and beta sheet
  • Tertiary structures-
    • 3-d that exposes binding domains etc
linkage maps
Linkage maps
  • YAC Yeast artificial chromosome &
  • BAC Bacterial artificial chromosome

-used to clone large pieces of DNA

-overlapping clones

  • Are genes linked?
organization of genomes
Organization of genomes
  • Groups of genes within a species

-Comparative Genomics

  • plastid genomes and mt genomes
how do we determine functions of genes45
How do we determine functions of genes?
  • Expression patterns
    • Northerns
    • RT-PCR
    • SAGE
    • Microarrays
  • Transgenics
    • insert genes what results?
  • Mutants
    • classical genetics
    • molecular genetics
  • And Functional Protein Assays
charles darwin
Charles Darwin
  • Descent with modification
    • species change through time and are related to a common ancestor
  • Natural Selection is the process by which this change occurs
understanding natural selection
Understanding Natural selection
  • acts on individuals though consequences occur in populations
    • Individual’s phenotype reason survived and reproduced
    • after a time this will change the distribution in the population,
    • what ultimately changes?
      • Gene pool
new alleles
New alleles
  • Point change is all that is needed
    • not always a "big deal"
      • neutral change
    • can be in Sickle cell anemia
gene duplication
Gene duplication
  • creates an additional copy of a gene
    • unequal cross-over
    • X-rays
  • Are these duplicates maintained in populations?
    • Psuedogenes
polyploidy
Polyploidy
  • additional set of chromosomes
    • Found in plants
    • Amphibians, invertebrates
      • Through a type of parthenogenesis
    • Triploid
      • Poor fertility
  • Hybridization or meiosis malfunction
homology
Homology
  • study of likeness (literal)
  • Similarity between species (or genes) that results from inheritance of traits from a common ancestor
    • Unless know of a common ancestor have to be careful when using this word.
slide53

b

b

b

a

a

a

Orthologous vs Paralogous Genes

a

Gene Duplication

Speciation

Species 1

Species 2

species
Species
  • All organisms alive today can trace their ancestry back to the origin of life some 3.8 billion years ago
    • Since then millions if not billions of branching events have occurred
  • Mechanisms have to be in place for change to occur
    • genetic drift and natural selection