Research in Computational Genomics

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Research in Computational Genomics
Mar Albà Evolutionary Genomics Group Research
Unit on Biomedical Informatics Universitat Pompeu
Fabra
UPC, April 1 2005
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1. The genetic information
2. The human genome project
3. Genomics techniques and research
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1. The genetic information
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The genetic information inheritance
1865 Mendel
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DNA is the hereditary material
1928 Griffith transforming principle
pneumonia
Infection of mice
Die
deadly bacteria
non deadly bacteria
Live
boiled deadly bacteria
Live

Die
1944 - Avery, MacLeod, McCarthy DNA is the
transforming principle


DNAse
Live


Die
protease
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DNA structure
1953 Watson and Crick discover the structure of
DNA
1953 Rosalind Franklin X difraction image of DNA
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DNA structure antiparallel double helix
nucleotides
A adenine G guanine C citosine T
thymine C-G A-T
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• RNA
• single strand
• uracil instead
• of thimine
• contains ribose
• instead of
• desoxiribose
• A-U
• C-G

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Proteins
QIKDLLVSSSTDLDTTLVLVNAIYFKGMWKTAFNAEDTREMPFHVTKQES
KPVQMMCMNNSFNVATLPAEKMKILELPFASGDLSMLVLLPDEVSDLERI
EKTINFEKLTEWTNPNTMEKRRVKVYLPQMKIEEKYNLTSVLMALGMTDL
FIPSANLTGISSAESLKISQAVHGAFMELSEDGIEMAGSTGVIEDIKHSP
ESEQFRADHPFLFLIKHNPTNTIVYFGRYWSP
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Proteins are made of amino acids
amino acid
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20 amino acids
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Proteins amino acid chain
Peptide bond
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DNA replication
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Transcription
The transcription of a gene may be off or on,
depending on the cell type and conditions.
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Translation
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Translation
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Genetic code
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DNA cloning
DNA ligase
vector with insert
DNA fragments
Vectors (replicating DNA)
transformation of bacteria
extraction
amplification
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DNA sequencing
resulting partial labelled fragments
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DNA sequencing
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2. The human genome project
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The human genome project
1953 - Discovery of the DNA double helix by
Watson and Crick 1995 - Haemophilus influenzae
genome 2001 - The first draft of the human
genome is published, covering approximately 94
of the genome (Public Consortium Celera) 2003
Human genome sequence complete
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2001 Draft of the human genome
15 February 2001
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IMIM (Institut Municipal dInvestigacions
Mèdiques, Barcelona) participates in the
annotation of the human genome
Josep Abril and Roderic Guigó
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Human genome 3.000.000.000 nucleotides
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Human chromosomes
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Whats in the human genome?
parasitic repetitive elements
gene coding part (2)
gene non- coding part
microsatellites
DNA long repeats
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Gene structure
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Comparison with other genomes
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Gene catalogue
30.000 genes
10.000 already known (cDNA)

• Gene prediction programmes
• Homology to other species
• ESTs (expressed sequence tags)

• - the functions of approximately half of the
  genes are not known !

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Parasitic repetitive elements
Nature, Feb. 15, 2001
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Parasitic repetitive elements Retrotransposition
cytoplasm
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3. Genomics techniques and research
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Genomics

• bioinformatics
• genome sequencing and annotation
• functional genomics
• systems biology

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Genome sequencing and annotation
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Exponential growth of DNA sequences
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How many genomes?
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Recently sequenced eukaryotic genomes
A.gossypii
A.gambiae
A.mellifera
C.intestinalis
T.rubripes
R.norvegicus
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How long does it take to sequence a genome?
bacteria 1 day fungus 1 week insect 1-2
months mammal 1-2 years
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Gene prediction

• DNA coding for protein sequences (exons) only
• accounts for 2 of the human genome
• Information we can use
• splice site signals
• statistics of coding sequences

gene
EXONS
PROTEIN
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Sequence similarity

• To predict genes we can also use sequence
  similarity
• searches to known proteins

alignment of protein sequences
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Microbial Genomes at NCBI
http//www.ncbi.nlm.nih.gov/genomes/MICROBES/Compl
ete.html
National Center for Biotechnology information,
National Institute of Health
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Functional annotation of all genes in a genome
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Ensembl Genome Browser
http//www.ensembl.org European Bioinformatics
Institute
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Ensembl Genome Browser
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Encode (NIH) Encyclopedia Of DNA Elements

• exhaustive analysis of 1 of the
• human genome
• identification of functional elements
• development and comparison of
• different computational methods

http//www.genome.gov/Pages/Research/ENCODE/ 2003-
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HapMap (Haplotype Map)
Variability map (single nucleotide polymorphism,
SNPs) in Africa, Asia and USA populations.
It will help identify genes involved
in complex disease, by association with
particular haplotypes.
haplotype variants
SNPs
http//www.hapmap.org/ 2002-
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Environmental Genome Shotgun Sequencing of the
Sargasso Sea J.Craig Venter et al. Science, Vol
304, Issue 5667, 66-74, 2 April 2004
1.045 billion base pairs 1800 genomic species
148 previously unknown bacterial phylotypes
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Functional genomics
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DNA microarrays high throughput analysis of gene
transcription
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chIp-chip analysis of protein binding DNA
fragments
cross-link protein and DNA
immunoprecipitation
eliminate protein
hybridize with DNA
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Protein-protein interactions yeast two hybrid
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Protein interaction networks
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Systems biology

• Development of mathematical methods to model the
• behaviour of biological systems, including all
  elements in
• the system and their interactions.

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National Center for Biotechnology Information
(USA) http//www.ncbi.nlm.nih.gov European
Bioinformatics Institute (UK) http//www.ebi.ac.
uk
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Acknowledgements Grup de Recerca en
Informàtica Biomèdica Ferran Sanz Grup de
Genòmica Computacional Roderic
Guigó Universitat Pompeu Fabra www.imim.es/grib
Genòmica Computacional GRIB