Science In Silico

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Science In Silico

• Carol J. Bult, Ph.D.
• Mouse Genome Informatics
• The Jackson Laboratory
• August 2002

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http//www.nature.com/genomics/human/papers/409860
a0_r_2.html
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Genomes on Parade
From M. Gerstein, Yale University, 2001
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Genome Sequencing Status 02(completed genomes)

• 16 Archaea
• 68 Bacteria
• 913 Viruses
• 8 Eukaryotes

http//www.ncbi.nlm.nih.gov/entrez/query.fcgi?dbG
enome
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Now Available in Draft Form!
The Mouse Genome
http//www.ncbi.nlm.nih.gov http//genome.ucsc.edu
http//www.ensemble.org
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Genetics is key to human health. The Jackson
Laboratory is key to genetics. http//www.jax.or
g
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Research Areas

• Cancer genetics
• Development and aging
• Immune system and blood disorders
• Neurological and sensory disorders
• Metabolic diseases
• Bioinformatics and statistical genetics

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Human
Why Mouse? Human and mouse genomes have
conserved blocks of genetic material
Mouse
Source Lisa Stubbs, Lawrence Livermore National
Lab
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Why Mouse? Humans and mice share many of
the same genes
Mouse- Human Comparative Map (2 cM around Acrb
gene)
http//www.informatics.jax.org
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Why Mouse? Humans and mice suffer from
similar diseases
Species Concordance for Susceptibility Alleles
for Hypertension
Hypertension QTL in Mouse Human (B. Paigen G.
Churchill)
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The Paradigm Shift in Biology

• The new paradigm, now emerging, is that all the
  genes will be known (in the sense of being
  resident in databases available electronically),
  and that the starting point of a biological
  investigation will be theoretical. An individual
  scientist will begin with a theoretical
  conjecture, only then turning to experiment to
  follow or test that hypothesis.
• - Walter Gilbert. Toward a paradigm shift in
  biology. Nature, 34999 (1991).

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http//cagle.slate.msn.com/news/gene/
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What is Bio-Informatics?

• The information technologies that bring together
  data, analytical software and methods, and people
  to drive biological discovery

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Data Integration is the Key to Making Sense of
Sequence
http//www.informatics.jax.org
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Exploring Biology on the Internet

• What disease are known to be associated with
  specific genes?
• Where are the genes in the genome?
• What are the characteristics of these genes?
• - i.e., size and structure
• What are known mutations in these genes?
• Where is the gene expressed?
• Do the mutations impact protein structure?
• Are there equivalent genes in other organism?
• Are the genes in other organisms associated with
  similar biological or disease processes as in
  humans?
• Are there gene and protein specific reagents like
  clones and antibodies available to use in
  experimental approaches?

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Concepts

• Basic genetics and molecular biology
• Connections between genes, variation, and disease
• Protein structure and function
• Comparative genomics
• Model organisms can yield insights into human
  biology and disease
• Orthology and paralogy

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Not all databases are created equal..

• Primary Databases (GenBank, EMBL, DDBJ)
• Original submissions by experimentalists
• Database staff organize but dont add additional
  information
• Derivative Databases (NCBI, Model organsim
  databases, etc.)
• Curated/expert review
• compilation and correction of data
• Computationally Derived
• Combinations
• Sifted Databases (GeneCards)
• Compilation of data from different derivative
  databases

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Todays Focus

• Given a sequence, gene, or disease of interest
  how do I use existing bioinformatics resources to
  find out the current state of knowledge?

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Start with a Known Gene or Disease
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http//www.ncbi.nlm.nih.gov80/entrez/query.fcgi?d
bOMIM
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p53
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Information for this Gene in OMIM
Links to Gene Details
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Survey of Mutations in this Gene
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http//archive.uwcm.ac.uk/uwcm/mg/hgmd0.html
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Link to NCBIs LocusLink
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Links!!
http//www.ncbi.nlm.nih.gov/LocusLink/index.html
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Map Details
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http//genome.ucsc.edu
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Links Again!!
Get the sequence of the Gene and corresponding
Protein
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http//bioinfo.weizmann.ac.il/cards/index.html
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Links!!
http//www.ncbi.nlm.nih.gov/LocusLink/index.html
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Details for the equivalent mouse gene
http//www.informatics.jax.org
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Start with a Sequence
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Get a sequence for this gene here
Or here
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Sequence in FASTA format
Jim Kents BLAST search tool http//genome.ucsc.e
du
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http//genome.ucsc.edu
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OMIM
LocusLink
PubMed
GeneCards
MGI
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Final Thoughts

• Biological databases are MUCH more interconnected
  than they used to be
• Easier to navigate to and from related data
• But can be confusing same information is
  presented in multiple ways. Easy to get lost in a
  maze of info.
• Dont assume that because you find information at
  a particular resource that they are the ones that
  produced or curated it!
• Many information resources (like GeneCards)
  sift data from many databases and re-display it
• Proper attribution for electronic resources is as
  important as for published information

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Human Genome Project Informationhttp//www.ornl.g
ov/hgmis/GOOGLE!http//www.google.com
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http//cagle.slate.msn.com/news/gene/