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Genomics

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The Human Genome Project

Mapping and Sequencing the Genomes of

Model Organisms

Data Collection and Distribution Ethical, Legal, and Social Considerations

Research Training

Technology Development

Technology Transfer

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A Few Genome Resources

NCBI Genome Resources

UCSC Human Genome Browser

EnsemblHuman Genome Server
http://www.ncbi.nlm.nih.gov/Genomes/index.htmlhttp://genome.ucsc.edu/http://www.ensembl.org/http://www.ensembl.org/http://www.ensembl.org/http://www.ensembl.org/http://genome.ucsc.edu/http://www.ncbi.nlm.nih.gov/Genomes/index.html

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Genome Sequencing Progress

NCBI Genome Sequence Repository

All organisms

Eukaryoticgenomes

Prokaryotic genomes

Archaeagenomes Viruses
http://www.ensembl.org/http://www.ensembl.org/http://www.ensembl.org/http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genomehttp://www.ncbi.nlm.nih.gov/PMGifs/Genomes/allorg.htmlhttp://www.ncbi.nlm.nih.gov/PMGifs/Genomes/euk.htmlhttp://www.ncbi.nlm.nih.gov/PMGifs/Genomes/euk.htmlhttp://www.ncbi.nlm.nih.gov/PMGifs/Genomes/eub.htmlhttp://www.ncbi.nlm.nih.gov/PMGifs/Genomes/a.htmlhttp://www.ncbi.nlm.nih.gov/PMGifs/Genomes/a.htmlhttp://www.ncbi.nlm.nih.gov/PMGifs/Genomes/vis.htmlhttp://www.ncbi.nlm.nih.gov/PMGifs/Genomes/vis.htmlhttp://www.ncbi.nlm.nih.gov/PMGifs/Genomes/a.htmlhttp://www.ncbi.nlm.nih.gov/PMGifs/Genomes/a.htmlhttp://www.ncbi.nlm.nih.gov/PMGifs/Genomes/eub.htmlhttp://www.ncbi.nlm.nih.gov/PMGifs/Genomes/euk.htmlhttp://www.ncbi.nlm.nih.gov/PMGifs/Genomes/euk.htmlhttp://www.ncbi.nlm.nih.gov/PMGifs/Genomes/allorg.htmlhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome

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Genome Sequencing

From NCBI, 5/2001
http://www.ncbi.nlm.nih.gov/PMGifs/Genomes/vis.htmlhttp://www.ncbi.nlm.nih.gov/PMGifs/Genomes/vis.htmlhttp://www.ncbi.nlm.nih.gov/PMGifs/Genomes/vis.html

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Human Genome Sequencing 2/11/2001

From NCBI
http://www.ncbi.nlm.nih.gov/PMGifs/Genomes/vis.htmlhttp://www.ncbi.nlm.nih.gov/PMGifs/Genomes/vis.html

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Human Genome Progress 2/11/2001

Total

sequence

(kb)

Non-redundant

sequence (kb)

Percentage of

genome

Finished 1,140,365 1,040,372 32.50%

Unfinished 3,547,899 1,951,344 61.00%

Total 4,688,264 2,991,716 93.50%

From NCBI
http://www.ncbi.nlm.nih.gov/PMGifs/Genomes/vis.htmlhttp://www.ncbi.nlm.nih.gov/PMGifs/Genomes/vis.htmlhttp://www.ncbi.nlm.nih.gov/PMGifs/Genomes/vis.htmlhttp://www.ncbi.nlm.nih.gov/PMGifs/Genomes/vis.htmlhttp://www.ncbi.nlm.nih.gov/PMGifs/Genomes/vis.htmlhttp://www.ncbi.nlm.nih.gov/PMGifs/Genomes/vis.htmlhttp://www.ncbi.nlm.nih.gov/PMGifs/Genomes/vis.htmlhttp://www.ncbi.nlm.nih.gov/PMGifs/Genomes/vis.htmlhttp://www.ncbi.nlm.nih.gov/PMGifs/Genomes/vis.htmlhttp://www.ncbi.nlm.nih.gov/PMGifs/Genomes/vis.htmlhttp://www.ncbi.nlm.nih.gov/PMGifs/Genomes/vis.htmlhttp://www.ncbi.nlm.nih.gov/PMGifs/Genomes/vis.htmlhttp://www.ncbi.nlm.nih.gov/PMGifs/Genomes/vis.html

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Microbial Genomes

Published complete microbial genomes

Microbial genomes and chromosomes in progr
http://www.ncbi.nlm.nih.gov/PMGifs/Genomes/vis.htmlhttp://www.ncbi.nlm.nih.gov/PMGifs/Genomes/vis.htmlhttp://www.ncbi.nlm.nih.gov/PMGifs/Genomes/vis.htmlhttp://www.tigr.org/tdb/mdb/mdbcomplete.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbcomplete.html

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Genome Informatics

Annotation and Analysis

Data Handling

Metabolic Reconstruction

Comparative Genomics

Functional Genomics
http://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.html

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Genome Project Organization

Cloning

Mapping

Sequencing

Annotation

Analysis
http://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.html

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Cloning and Mapping
http://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.html

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Cloning

Large YACs

1 Mb

BACs 100 - 200 Kb

Intermediate Cosmids Lambda clones

Small Plasmids; M13
http://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.html

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Mapping

Establishment of Guideposts

Aids in Assembly

Error Checking

Useful in mapping of genetic disorders
http://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.html

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Genetic Maps

Cytogenetic markers

Linkage maps Polymorphic loci screened by PCR to

determine inheritence patterns

Produce linkage map with nearby loci
http://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.html

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Physical Maps

Radiation Hybrid/YACs/Cosmids Restriction Sites Sequence Tagged Sites

100 Kb resolution needed 30,000 STSs

Expressed Sequence Tags

Detection PCR Hybridization FISH

Fluoresecent in situ Hybridization
http://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.html

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Human Genome STS Mapping Strategy

STS Content Mapping Screen YACs by PCR

Radiation Hybrid Mapping Screen RH Cell lines by PCR

Genetic Mapping

PCR Screening of polymorphic loci Combine above to produce an integrated

map
http://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.html

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Mapping Resolution

YAC mapping 1 Mb

Radiation hybrid mapping 10 Mb

Genetic map 30 Mb
http://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.html

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GeneMap98

Integrated Human Genetic Map

Over 30,000 unique gene-based markers 100 Kb resolution

http://www.ncbi.nlm.nih.gov/genemap98/
http://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.tigr.org/tdb/mdb/mdbinprogress.htmlhttp://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/

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Map Integration

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Human Chromosome 1 Genetic Map

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Human Chromosome 1 Combination Map

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Sequencing
http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/

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Sequencing Methods

Random Shotgun

Ordered Shotgun

Directed Primer Walking

Direct genomic sequencing
http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/

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Random Shotgun Sequencing

Randomly shear or cut DNA into small pieces 2-4 Kb

Clone into M13, pUC or some other sequencingvector

Sequence the clones from both ends

Rely on the computer to assemble the

sequences into one (or as few as possible)

contigs
http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/

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Shotgun Sequencing Statistics

Lander and Waterman equation poisson distribution

Po = e-m probability that a base is not sequenced

where m=sequence coverage
http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/

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H. influenza Sequencing

For 1X random sequence coverage = 1.8 Mb P = 0.37 (63% of the bases are sequenced)

To get > 99% of the bases sequenced 5X coverage = 8.74 Mb of sequence

Po = e-5 = 0.0067

This coverage would leave approx. 128 gaps of

about 100 bp in size From Science 269:496-512. 1995
http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/

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Ordered Sequencing

Generate a set of large sequence clones in

lambda phage

May be subcloned from YACs or BACs as necessary End sequence the lambda clones and order the

clones to produce a map of the genome

Choose a minimal tiling path of the genome from

the ordered lambda clones
http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/

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Ordered Sequencing...

Shear and subclone the lambda inserts

that comprise the minimal tiling set into

sequencing vectors Shotgun sequence and assemble each of

these lambda inserts individually

Assemble all sequences into one,contiguous genome
http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/

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Directed Sequencing

Process used for finishing following the

shotgun sequencing phase

Gap closure Use specific sequencing primers to extend

appropriate clones into gap regions

Use specific sequencing primers tosequence directly from genomic DNA
http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/

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Sequence Assembly
http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/

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Assembly of Shotgun Fragments

For H. influenzae (TIGR) 1.8 Mb 24,304 Sequence fragments were generated

for the random assembly phase 11,631,485 bases

Generated 140 contigs

Assembled using the TIGR Assembler 30 hours of cpu time
http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/

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phred/phrap/consed

Widely used programs for sequence: base calling (phred)

assembly (phrap) editing (consed)

Developed at the University ofWashington Phil Green (phrap) Brent Ewing (phred) David Gordon (consed)
http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/

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Genome Annotation and Analysis

Pattern Matching
http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/

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Sequence Annotation

ORF identification

Frameshift resolution

Genome map construction

Functional assignments

Metabolic pathway assignment

Metabolic pathway Reconstruction

Comparative analysis
http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/

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Annotation Tools

Semi-automated

Manual
http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/

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MAGPIE

Multipurpose Automated Genome Project

Investigation Environment

Terry Gaasterland et. al. http://genomes.rockefeller.edu/magpie/magpie.htmlAutomated

Semi-automated analysis tool for microbial

genome projects
http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://www.ncbi.nlm.nih.gov/genemap98/http://genomes.rockefeller.edu/magpie/magpie.htmlhttp://genomes.rockefeller.edu/magpie/magpie.htmlhttp://genomes.rockefeller.edu/magpie/magpie.htmlhttp://genomes.rockefeller.edu/magpie/magpie.htmlhttp://genomes.rockefeller.edu/magpie/magpie.htmlhttp://genomes.rockefeller.edu/magpie/magpie.htmlhttp://genomes.rockefeller.edu/magpie/magpie.html

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MAGPIE Example

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Non-Automated Analysis and Prediction

The Ureaplasma urealyticum genome

database

Run analysis tool Parse results

Dump results into the database

View results

Manually annotate

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Genomic Sequence Database

Data Storage Sequence

Gene MapAnnotation

User Interface

Web browser Customizable

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The Ureaplasma urealyticum Genome Project

Uu - 751,719 bp http://genome.microbio.uab.edu/uu/uugen.htm

Web-based genome analysis tool
http://genome.microbio.uab.edu/uu/uugen.htmhttp://genome.microbio.uab.edu/uu/uugen.htmhttp://genome.microbio.uab.edu/uu/uugen.htmhttp://genome.microbio.uab.edu/uu/uugen.htmhttp://genome.microbio.uab.edu/uu/uugen.htmhttp://genome.microbio.uab.edu/uu/uugen.htmhttp://genome.microbio.uab.edu/uu/uugen.htmhttp://genome.microbio.uab.edu/uu/uugen.htmhttp://genome.microbio.uab.edu/uu/uugen.htm

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Annotation Problems

Problems with existing sequence databases Incomplete datasets Skewed datasets Incorrectly annotated records

Annotations based on experimental vs. predicteddata

Nomenclature differences Transitive errors in gene function predictions Functional predictions for hypothetical genes

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Metabolic Pathway Reconstruction

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Metabolic Pathway Reconstruction

Role assignment

Extract metabolic pathways from genomes

Navigation and analysis

Pathway editing

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Metabolic Assignments

Amino acid Biosynthesis Biosynthesis of cofactors, prosthetic groups, and carriers Cell envelope Cellular processes Central intermediary metabolism

Energy metabolism Fatty acid and phospholipid metabolism Purines, pyrimidines, nucleosides, and nucleotides Regulatory functions Replication Transcription Translation Transport and binding proteins Other categories, Unassigned Hypothetical

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750,001

700,001

650,001

600,001

550,001

500,001

450,001

400,001

350,001

300,001

250,001

200,001

150,001

100,001

50,001

1

750,000

751,719

700,000

650,000

600,000

550,000

500,000

450,000

400,000

350,000

300,000

250,000

200,000

150,000

100,000

50,000

Cofactor BiosynthesisCell envelopeCellular processesCentral Intermediary Metabolism

Energy MetabolismFatty Acid MetabolismHypothetical

Nucleotide Metabolism

ReplicationTranscriptionTranslationTransport

RNA

tRNA

Other

Ureaplasma urealyticum Gene Map

U G M G

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Amino acid Biosynthesis

Biosynthesis of cofactorsCell envelope

Cellular processes

Central intermediary metabolism

Energy metabolism

Fatty acid - phospholipidsHypothetical

Other categories

Purines, pyrimidines

Regulatory functions

Replication

Transcription

Translation

Transport and binding proteins

Unassigned

Total

1

1019

13

15

23

6293

1

18

4

45

17

100

37

4

606

0.2%

1.7%3.1%

2.1%

2.5%

3.8%

1.0%48.3%

0.2%

3.0%

0.7%

7.4%

2.8%

16.5%

6.1%

0.7%

100.0%

0

726

15

7

30

7169

3

20

4

31

19

99

35

7

479

0.0%

1.5%5.4%

3.1%

1.5%

6.3%

1.5%35.3%

0.6%

4.2%

0.8%

6.5%

4.0%

20.7%

7.3%

1.5%

100.0%

Role

Uu Genes Mg Genes

#Percent

of Total #Percent

of Total

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EcoCyc

Peter D. Karp, PhD

SRI International Menlo Park, CA

http://ecocyc.pangeasystems.com/ecocyc/

ecocyc.html
http://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.html

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Pathway Reconstruction

Genomic

Maps

Genes

Gene Products

Reactions (Compounds)

Pathways

Metabolic Network

Annotated Genome

List of Genes/ORFs

List of Gene Products

DNA Sequence

Cell

Adapted from P. Karp, Pangea Systems
http://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.html

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glyceraldehyde 3-phosphate

dehydrogenase

1.2.1.12

fructose-6-phosphate

glucose-6-phosphate

fructose-1,6-bisphosphate

pyruvate3-phosphoglycerate

3-phospho-D-glyceroyl-phosphate

glyceraldehyde-3-phosphate

phosphoglucose isomerase

6-phosphofructokinase

fructose bisphosphate aldolase

phosphoglycerate kinase

glucose-1-phosphate

phosphoglucomutase

glyceraldehyde-3-phosphate

dehydrogenase

1.2.1.9

Glycolysis in Uu?

?
http://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.html

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Uu Energy Metabolism

Glycolysis Missing several components

Pentose-phosphate pathway Only 2/8 enzyme complexes present

Proton motive force - ATP synthasecomplex

Urease Gene Complex Biologically relevant
http://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.html

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Comparative Genomics

What makes one organism different from

all other organisms?

Molecular Biology Physiology

Pathogenesis

Epidemiology

Genetics
http://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.html

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Ortholog Comparisons

Uu to Mg genes: 324 53% of Uu; 67% of Mg 71 hypothetical

Mh to Mg genes: 314 41% of Mh; 57% of Mg 55 hypothetical (2 unique hypothetical)

Mh to Uu genes: 330 47% of Uu; 43% of Mh 82 hypothetical (19 unique hypothetical)
http://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.html

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M. genitalium - M. pneumoniae Gene Order

0

100,000

200,000

300,000

400,000

500,000

0 100,000 200,000 300,000 400,000 500,000 600,000 700,000 800,000

M. pneumoniae Gene PositionM. pneumoniae Gene Position

M. g

enitaliu

mGene

Po

sition

M. g

enita

liu

mGe

ne

Positi o

n
http://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.html

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M. genitalium - U. urealyticum Gene Order

0

100,000

200,000

300,000

400,000

500,000

0 100,000 200,000 300,000 400,000 500,000 600,000 700,000

U. urealyticum Gene Position

M. g

enitaliu

mGe

ne

Positi o

n
http://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.html

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Paralog Analysis

Identification of conserved, paralogousgroups

All against All comparison Genes within one organism

Identifies groups of related genes Primary sequence Structure Function

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Uu Paralogous Clusters >3

4 tRNA synthetase 4 Translation factors 4 Hypothetical membrane lipoprotein 5 ATP synthase alpha, beta chains 6 MBA 7 Hypothetical membrane lipoprotein

8 Hypothetical 10 Iron transporters 13 Transporters
http://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.html

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Functional Genomics

Gene Expression

Gene Regulation

Genome-wide Mutagenesis
http://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.html

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Expression Arrays

Cell growth in different environments

Isolate cDNAs

Measure expression using array technology Create database of expression information

Display information in an easy-to-use format Show ratio of expression under different conditions
http://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.html

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Putting it all together
http://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.html

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From F. Blattner, U. Wisc.
http://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.html

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Chromosome Views

Ensembl view

UC Santa Cruz view

NCBI View
http://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.html

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A Final Caveat

The difficulty of identifying genes in

anonymous vertebrate sequences

Claverie JM, Poirot O, Lopez F

Comput Chem 1997;21(4):203-14

The identification of genes in newly determined vertebrate genomic

f t i i l t i ibl t k I
http://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.htmlhttp://ecocyc.pangeasystems.com/ecocyc/ecocyc.html

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sequences can range from a trivial to an impossible task. In a

statistical preamble, we show how "insignificant" are the individual

features on which gene identification can be rigorously based:

promoter signals, splice sites, open reading frames, etc. The practicalidentification of genes is thus ultimately a tributary of their

resemblance to those already present in sequence databases, or

incorporated into training sets. The inherent conservatism of the

currently popular methods (database similarity search, GRAIL) willgreatly limit our capacity for making unexpected biological

discoveries from increasingly abundant genomic data. Beyond a very

limited subset of trivial cases, the automated interpretation (i.e.

without experimental validation) of genomic data, is still a myth. On

the other hand, characterizing the 60,000 to 100,000 genes thought to

be hidden in the human genome by the mean of individual

experiments is not feasible. Thus, it appears that our only hope of

turning genome data into genome information must rely on drastic

progresses in the way we identify and analyze genes in silico.

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Only One Final Word of Wisdom...

...although the computer is a wonderful

helpmate for the sequence searcher and

comparer, biochemists and molecularbiologists must guard against the blind

acceptance of any algorithmic output;

given the choice, think like a biologist and

not a statistician. - Russell F. Doolittle, 1990
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