Professional Development Course 1 – Molecular Medicine Genome Biology June 12 , 2012

Professional Development Course 1 –Molecular Medicine

Genome BiologyJune 12, 2012

Ansuman Chattopadhyay, PhDHead, Molecular Biology Information ServicesHealth Sciences Library SystemUniversity of [email protected]

http://www.hsls.pitt.edu/guides/genetics

mailto:[email protected]


Genomic achievements since the Human Genome Project

http://www.hsls.pitt.edu/molbio



Objective

Organism Whole Genome Sequence Databases

Genome Browsers




Topics

Genome Sequencing Projects

NCBI Genome resources Integrated Microbial Genome UCSC Genome Bioinformatics

Genome Browsers

UCSC Genome Browser UCSC Table Browser NCBI Map viewer Generic Genome Browser (Gbrowse)




Genome Biology

Human Genome Project Video




http://www.youtube.com/watch?v=_EK3g6px7Ik

Chromosome Structure




Genome Biology: Karyotype

Adapted from NGHRI

Trisomy 21

Monosomy X




Genome Biology: Karyotype

NHGRI




Genome Biology: Molecular Cloning

p53

CFTRNFkB

8 September, 1989




Genome Biology : Time Line

1976

RNA Bacteriophage MS2

2001

Human Genome Draft Seq

2003

Published Complete Human Ref Genome

2007

Diploid Genome seq ofan Individual Human

2011

Published Complete Genomes: 1863 organisms

1995

HaemophilusInfluenza

2008

Jim Watson Genome

Yeast

1996

1998

C. elegans

2002

Drosophila



DNA Sequencing Cost




Oxford Nanopore

A 20-node installation, using 8,000-nanopore cartridges, is expected

to deliver a complete human genome at 50-fold coverage in 15 minutes, according to the company, or 3 terabases of data per day, based on a sequencing

speed of 300 bases per second. For that setup, the cost per gigabase is expected to be under $10.




Organism Whole Genome Sequences

2001 2012




Organism Whole Genome Sequences

HumanMouse

Rat

Dog

Cow

Chimp

Rabbit

……..




Genomes OnLine Database (GOLD) http://www.genomesonline.org/index.htm

Global comprehensive access to information regarding complete and ongoing genome projects, as well as metagenomes & metadata


http://www.genomesonline.org/index.htm


http://www.genomesonline.org/cgi-bin/GOLD/bin/gold.cgi

Genome Resources



http://www.genomesonline.org/

http://genome.ucsc.edu/

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

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

Search for organism’s whole genome

sequence




Genome Resources

NCBI: Genomes Resources : Link

Genome: http://www.ncbi.nlm.nih.gov/sites/entrez?db=genome

JGI: Integrated Microbial genome Link


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

http://www.ncbi.nlm.nih.gov/sites/entrez?db=genome

http://img.jgi.doe.gov/cgi-bin/pub/main.cgi



NCBI Genome



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

NCBI BioProject Query: Check the status of genome sequencing

for an organism, such as honey bee.

Answer: Enter search term under BioProject

Select the appropriate organism

The BioProject summary page will provide information of available projects and sequencing status

Click on Project Type for more detailed information

Explore Related Resources




Link to the video tutorial:http://media.hsls.pitt.edu/media/clres2705/rabbit.swf

Resources

• NCBI Genome Project: http://www.ncbi.nlm.nih.gov/genomeprj• NCBI Genome: http://www.ncbi.nlm.nih.gov/sites/genome

Find the genomic sequence for an organism, such as rabbit.


http://media.hsls.pitt.edu/media/clres2705/rabbit.swf

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

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

NCBI Genome Project A collection of complete and in-progress large-scale sequencing, assembly,

annotation, and mapping projects for cellular organisms. The database is organized into organism-specific overviews that function as portals for browsing and retrieving projects pertaining to each organism.

CLICKRabbit






NCBI Genome Project : Rabbit Genome




NCBI Genome Project : Rabbit Genome





Link to the video tutorial:http://media.hsls.pitt.edu/media/molbiovideos/img.swf

Resources

Integrated Microbial Genome (IMG):http://img.jgi.doe.gov/cgi-bin/w/main.cgi

Find the genomic sequence for a bacteria, such as Salmonella enterica


http://media.hsls.pitt.edu/media/clres2705/img.swf

http://img.jgi.doe.gov/cgi-bin/w/main.cgi

Human genome sequence




Genomic achievements since the Human Genome Project




http://goo.gl/bsZdN


http://goo.gl/bsZdN



Genome Biology: Structural Variations




Genome Reference Consortium

Link to the PLoS Biology paper on the GRC : http://goo.gl/30Xun


http://goo.gl/30Xun



NCBI Genome Resourceshttp://www.ncbi.nlm.nih.gov/guide/genomes/






What is a Genome Browser?

Genome Browsers enable researchers to visualize & browse entire genomes with annotated data including:

• gene prediction and structure • proteins• expression• regulation• variation• comparative analysis• etc.

Annotated data is usually from multiple diverse sources.




Eukaryotic Genome Browsers


Display: Vertical

Display: Horizontal


http://genome.ucsc.edu/cgi-bin/hgGateway

http://useast.ensembl.org/index.html

http://gmod.org/wiki/GBrowse

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

Non-vertebrate Genome Browsers



http://img.jgi.doe.gov/

http://www.ncbi.nlm.nih.gov/genomes/GenomesHome.cgi?taxid=10239

http://cmr.jcvi.org/tigr-scripts/CMR/CmrHomePage.cgi

http://www.vbrc.org/

Genome Browsers

The Big Three

NCBI MapViewer UCSC Genome Browser EBI Ensemble

Generic Genome Browser

(Gbrowse)

Display: Vertical

Display: Horizontal




UCSC Genome Browser




UCSC Genome Browser Default Tracks



UCSC Genome Browser Page


mRNA and EST Tracks

Expression (such as microarray)

Comparative Genomics• As a group• Individual species

Variation and Repeats(including SNPs, copy number variation)

Groups of data (Tracks)

ENCODE Tracks

Phenotype and Disease Tracks

Regulation (including TFBS)


Navigating the Human Genome

Browse the region of human chromosome 7 between 54,318043 to 55,974,438 bp (chr7:54,318,043-55,974,438)





Link to the video tutorial:http://media.hsls.pitt.edu/media/clres2705/ucsc_genes.swf

Resource

UCSC Genome Browser: http://genome.ucsc.edu/

Browse the region of human chromosome 7 between 54,318043 to 55,974,438 bp.

What genes are present in this region ?


http://media.hsls.pitt.edu/media/clres2705/ucsc_genes.swf

http://media.hsls.pitt.edu/media/clres2705/ucsc_genes.swf


UCSC Genome Browser




http://genome.ucsc.edu/cgi-bin/hgGateway

UCSC Genome Browser: Navigating a Genomic Region




What genes are present in this region?



Bioinformatics Institutionshttp://www.ebi.ac.uk/http://www.ncbi.nlm.nih.gov/


http://www.ebi.ac.uk/

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




What is RefSeq ?



NCBI Sequence Databases

GenBank archival database of nucleotide sequences

from >160,000 organisms More info

RefSeq based on GenBank record, non-redundant

expert verified databases of reference sequences More info


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

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


International Nucleotide Sequence Database Collaboration



Primary Vs Derivative databases



RefSeq Scope & Accessions

Genomic DNA NC_123456 - complete genome, complete

chromosome, complete plasmid NG_123456 - genomic region NT_123456 - genomic contig

mRNA - NM_123456 Protein - NP_123456

more about RefSeq scope and accessions...


http://www.ncbi.nlm.nih.gov/RefSeq/key.html




RefSeq Status Codes

Provisional Reviewed Predicted Genome Annotation

more about RefSeq status codes












Display Options


Hide: removes a track from view

Dense: all items collapsed into a single line

Squish: each item = separate line, but 50% height + packed

Pack: each item separate, but efficiently stacked (full height)

Full: each item on separate line





Gene Description



Gene Description


Informative description

other resource links

microarray data

mRNA secondary structure

links to sequences

protein domains/structure

orthologs in other species

Gene Ontology™ descriptions

mRNA descriptions

pathways

genetic association studies

comparative toxicology

gene model



Find SNPs present in this region




Link to the video tutorial:http://media.hsls.pitt.edu/media/clres2705/ucsc_snp.swfFile: UCSC_part2.swf

Resource

UCSC Genome Browser: http://genome.ucsc.edu/

Browse the region of human chromosome 7 between 55,033,691 to 55,282,150 bp.

What genetic variations are present in this region ?Retrieve the DNA sequence of this genomic region showing

SNPs in red and all gene exons in blue


http://media.hsls.pitt.edu/media/clres2705/ucsc_snp.swf














BLAT: Map a protein sequence into the

genome




UCSC Blat: Place a Peptide Seq into the Genome

Peptide Seq:NKSSHFYSNVGLQIQTYELQESNVQLKLTVVET

Nucleotide seq:AAATCCTCACATTTTTACTCAAATGTTGGACTTCAAATTCAGACATATGAACTTCAGGAAAGC AATGTTCA





Link to the video tutorial:http://media.hsls.pitt.edu/media/clres2705/blat.swfFile: Blat.swf

Resource

UCSC BLAT: http://genome.ucsc.edu/cgi-bin/hgBlat?command=start

Place a mRNA or peptide sequence into the human genome


http://media.hsls.pitt.edu/media/clres2705/blat.swf

http://genome.ucsc.edu/cgi-bin/hgBlat?command=start

UCSC Blathttp://genome.ucsc.edu/cgi-bin/hgBlat


http://genome.ucsc.edu/cgi-bin/hgBlat



UCSC Blat




UCSC Blat

Peptide Seq:NKSSHFYSNVGLQIQTYELQESNVQLKLTVVET




Thank you!Any questions?

Carrie Iwema Ansuman [email protected] [email protected] 412-383-6887 412-648-1297






Documents

Professional Development Course 1 – Molecular Medicine Genome Biology June 12 , 2012