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Genomics, Proteomics, and Bioinformatics. Biology 224 Instructor: Tom Peavy January 29, 2008. 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

January 29, 2008

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?

slide5

Top ten challenges for bioinformatics

[1] Precise models of where and when transcription

will occur in a genome (initiation and termination)

[2] Precise, predictive models of alternative RNA splicing

[3] Precise models of biological pathways;

ability to predict cellular responses to external stimuli

[4] Determining protein:DNA, protein:RNA, protein:protein

recognition codes

[5] Accurate ab initio protein structure prediction

slide6

Top ten challenges for bioinformatics

[6] Rational design of small molecule inhibitors of proteins

[7] Mechanistic understanding of protein evolution

[8] Mechanistic understanding of speciation

[9] Development of effective gene ontologies:

systematic ways to describe gene and protein function

[10] Education: development of bioinformatics curricula

Source: Ewan Birney,

Chris Burge, Jim Fickett

slide7

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
slide9

bioinformatics

medical

informatics

public health

informatics

algorithms

databases

infrastructure

Tool-users

Tool-makers

slide10

DNA

RNA

protein

phenotype

protein

sequence

databases

cDNA

ESTs

UniGene

genomic

DNA

databases

slide11

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

slide12

Growth of GenBank

Base pairs of DNA (billions)

Sequences (millions)

1982

1986

1990

1994

1998

2002

Updated 8-12-04:

>40b base pairs

Year

slide13

Press Release (August 22, 2005)

    • 100 gigabases of sequence data

(NCBI, EMBL, & DDBJ)

    • over 165,000 organisms
slide14

The growth of GenBank. The blue area shows the total number of bases including those from whole genome shotgun sequencing projects (WGS). The checkered area shows only the non-WGS portion. With release 149, the number of WGS bases exceeded the number of bases in the traditional GenBank divisions.

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)
slide31

Synonymous

Substitution

Non-synonymous

Substitution

central dogma
Central Dogma
  • DNA  RNA  protein
  • sequence  structure  function  evolution
slide33

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 genes1
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 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.
slide52

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