the british columbia cancer agency genome sciences centre
TRANSCRIPT
Microsoft PowerPoint - TUPC_AGM.pptSciences Centre:
The BC Cancer Agency Genome Sciences Centre...
•Mandate: to become a world-class Genome Centre.
•Department of the British Columbia Cancer Agency Research Centre.
•Located on the third floor of the Vancouver Cancer Clinic.
•Moved into current lab space Dec. 13, 1999.
•21,000 sf interim space divided into Structural Genomics and bioinformatics (19,500 sf) and Functional Genomics (1,500 sf). All space is rented.
•Renovation, start-up and some operating funds provided by the BC Cancer Foundation. Major projects are grant funded.
•Focus initially is on large-scale high-throughput mapping, sequencing, gene expression and bioinformatics projects.
Staff
• 120 employees, including: – 6 PIs – 12 trainees – 50 bioinformatics staff
Funding
What is “the Genome?”
The Central Dogma of Molecular Genetics
DNA RNA Protein
From DNA to Protein
Rationale There are a staggering number of cells in the human body.
Most of these cells contain genetic material; all of the cells contain protein and other chemical entities.
The information encoded in the genetic material is somehow “understood” and interpreted by cells.
The correct cellular interpretation is essential for normal development and health of the organism.
Disease can result due to complex interactions between largely unidentified genes and poorly understood environmental factors.
To identify the many unknown genes involved in development and disease, tools capable of “high throughput” and applicable at “large scale” are required.
These are the tools of Genomics.
What is genomics?
According to http://genomics.ucdavis.edu/what.html:
“Genomics is operationally defined as investigations into the structure and function of very large numbers of genes undertaken in a simultaneous fashion.”
Genome BC sponsored technologies
•Bioinformatics (S. Jones & A. Siddiqui, BCCA GSC & F. Ouellette, CMMT)
•DNA sequencing (M. Marra & R. Holt, BCCA GSC; B. Koop, U.Victoria)
•BAC fingerprint mapping (M. Marra & J. Schein, BCCA GSC)
•Model organism genetics (D. Moerman, UBC)
•Genotyping (A. Brooks-Wilson & M. Marra, BCCA GSC)
•cDNA Microarrays (C. Nelson, JBRC & VGH)
•Proteomics (R. Olafson, U.Victoria)
Genome B.C. Research Portfolio*
Environment Microbial Envirogenomics (UBC)
Forestry Forestry Genomics (UBC)
Health Studies of Early Stage Cancer (B.C. Cancer Agency) Bioinformatics of Mammalian Gene Expression (B.C. Cancer Agency) Atlas of Gene Expression in Mouse Development (B.C. Cancer Agency) The Nematode as a Model Organism (UBC) Genomics of the Pathogen Cryptococcus neoformans (UBC) Expression Profiles of Cells & Tissues C. elegans (SFU & UBC)
*Courtesy B. Schmidt, Genome BC
Automation
Bioinformatics
Genome sequence of the SARS Coronavirus (Tor 2)
Chronology February 28: Dr. Carlos Urbani examines patient in Hanoi with
atypical pneumonia
March 27: Decision to proceed
April 6: RNA received from NML / BCCDC
April 11, 9:30 pm: First sequences available
April 11, 9:41 pm: First sequence assembly
April 12, 2:25 am: First whole-genome assembly
April 12, 11:30 pm: Draft whole genome assembly available on web site
April 14, 5:30 pm: Finished sequence; error rate ~1 / 1 billion
Coronavirus Biology
A SARS cDNA Library AAAAA
DNA Sequencing
First reads searched (BLASTX) against genbank ‘nr’
First set of 96 end reads from SARS2 cDNA library finally available
9:30 pm9:30 pm – April 11 (Fri)
What was known about coronavirus genomes: - single stranded RNA - approximately 30 kb - 5’ cap structure - 3’ poly A tract
‘What’s up…’
-- Jeff Stott, Vancouver biologist, walks in and scares Yaron at the computer
1:00 pm1:00 pm
5:00 am5:00 am
On going assembly analysis throughout the day as sequence data accrued…
Build 7.4 genome assembly imported into AceDB for initial biological analysis
8:00 am8:00 am
April 12 (Sat)
11:30 pm11:30 pm
April 12 (Sat)
11:30 pm11:30 pm – April 12 (Sat)
Final biological analysis of Build 11.5 in AceDB conducted and completed draft genome assembly (29,736 bp) deposited online for download.
GROUP I
GROUP II
GROUP III
GROUP I
GROUP II
GROUP III
GROUP II GROUP III
Phylogenetic trees of protein sets with three other known coronaviral groups
Transcription Regulatory Sequences
Invited response to comment of Peng Shi et al.
On the quality of the Tor2 SARs-CoV genome sequence.
Marco A. Marra*, Jaswinder Khattra and Yaron S. N. Butterfield Canada’s Michael Smith Genome Sciences Centre
British Columbia Cancer Agency Vancouver, British Columbia
Canada V5Z 4E6 * To whom correspondence should be addressed.
Phone: 604-877-6084 FAX: 604-877-6085 Email: [email protected]
Marra MA, Jones SJM, Astell C, Holt RA, Brooks- Wilson AR, and 53 others. The Genome Sequence of the SARS-Associated Coronavirus. Sciencexpress 2003; 1126/science.1085953. In Press.
This publication describes the rapid generation of the complete and accurate sequence of the SARS- associated coronavirus. The Genome Sciences Centre generated and end-sequenced cDNAs, and then assembled these sequences into the final ~29 kilobase genome sequence. The entire effort took about six days, demonstrating that genome sequencing of a new viral pathogen could be considered a legitimate part of a "rapid response" to an emerging infectious disease.
Significance
• Clones distributed to academics and industry
• Stated purposes include expression of proteins (vaccines, neutralizing antibodies) and development of PCR and other diagnostic tools
What made it possible?
• The realization it should and could be done • The NML / BC CDC connection • Trained staff available • State-of-the-art equipment commissioned
and software installed
The initial and ongoing support from BCCA, GBC / GC, WD, NCI, NHGRI,…..
Special Challenges Development of new technologies continues apace, with the aim of increasing throughputs, decreasing operating costs and more sophisticated approaches and tools.
State of the art robotics and computers have a life span of ~2 years. A minimum requirement for maintenance of a nationally and internationally competitive research community requires an ongoing commitment to access and operate state of the art technologies.
Effective training of young genome researchers relies on the existence of established genomics research programs and platforms.
Retention of established researchers relies on their ability to conduct internationally competitive research.
Government and non-profit funding
CIHRNRCHRDCIndustry CanadaWED
BC BiotechKinexusKinetekXenonQLT
BC Cancer Agency
BC Cancer Agency Genome Sciences Centre
and
The BC Cancer Agency Genome Sciences Centre...
•Mandate: to become a world-class Genome Centre.
•Department of the British Columbia Cancer Agency Research Centre.
•Located on the third floor of the Vancouver Cancer Clinic.
•Moved into current lab space Dec. 13, 1999.
•21,000 sf interim space divided into Structural Genomics and bioinformatics (19,500 sf) and Functional Genomics (1,500 sf). All space is rented.
•Renovation, start-up and some operating funds provided by the BC Cancer Foundation. Major projects are grant funded.
•Focus initially is on large-scale high-throughput mapping, sequencing, gene expression and bioinformatics projects.
Staff
• 120 employees, including: – 6 PIs – 12 trainees – 50 bioinformatics staff
Funding
What is “the Genome?”
The Central Dogma of Molecular Genetics
DNA RNA Protein
From DNA to Protein
Rationale There are a staggering number of cells in the human body.
Most of these cells contain genetic material; all of the cells contain protein and other chemical entities.
The information encoded in the genetic material is somehow “understood” and interpreted by cells.
The correct cellular interpretation is essential for normal development and health of the organism.
Disease can result due to complex interactions between largely unidentified genes and poorly understood environmental factors.
To identify the many unknown genes involved in development and disease, tools capable of “high throughput” and applicable at “large scale” are required.
These are the tools of Genomics.
What is genomics?
According to http://genomics.ucdavis.edu/what.html:
“Genomics is operationally defined as investigations into the structure and function of very large numbers of genes undertaken in a simultaneous fashion.”
Genome BC sponsored technologies
•Bioinformatics (S. Jones & A. Siddiqui, BCCA GSC & F. Ouellette, CMMT)
•DNA sequencing (M. Marra & R. Holt, BCCA GSC; B. Koop, U.Victoria)
•BAC fingerprint mapping (M. Marra & J. Schein, BCCA GSC)
•Model organism genetics (D. Moerman, UBC)
•Genotyping (A. Brooks-Wilson & M. Marra, BCCA GSC)
•cDNA Microarrays (C. Nelson, JBRC & VGH)
•Proteomics (R. Olafson, U.Victoria)
Genome B.C. Research Portfolio*
Environment Microbial Envirogenomics (UBC)
Forestry Forestry Genomics (UBC)
Health Studies of Early Stage Cancer (B.C. Cancer Agency) Bioinformatics of Mammalian Gene Expression (B.C. Cancer Agency) Atlas of Gene Expression in Mouse Development (B.C. Cancer Agency) The Nematode as a Model Organism (UBC) Genomics of the Pathogen Cryptococcus neoformans (UBC) Expression Profiles of Cells & Tissues C. elegans (SFU & UBC)
*Courtesy B. Schmidt, Genome BC
Automation
Bioinformatics
Genome sequence of the SARS Coronavirus (Tor 2)
Chronology February 28: Dr. Carlos Urbani examines patient in Hanoi with
atypical pneumonia
March 27: Decision to proceed
April 6: RNA received from NML / BCCDC
April 11, 9:30 pm: First sequences available
April 11, 9:41 pm: First sequence assembly
April 12, 2:25 am: First whole-genome assembly
April 12, 11:30 pm: Draft whole genome assembly available on web site
April 14, 5:30 pm: Finished sequence; error rate ~1 / 1 billion
Coronavirus Biology
A SARS cDNA Library AAAAA
DNA Sequencing
First reads searched (BLASTX) against genbank ‘nr’
First set of 96 end reads from SARS2 cDNA library finally available
9:30 pm9:30 pm – April 11 (Fri)
What was known about coronavirus genomes: - single stranded RNA - approximately 30 kb - 5’ cap structure - 3’ poly A tract
‘What’s up…’
-- Jeff Stott, Vancouver biologist, walks in and scares Yaron at the computer
1:00 pm1:00 pm
5:00 am5:00 am
On going assembly analysis throughout the day as sequence data accrued…
Build 7.4 genome assembly imported into AceDB for initial biological analysis
8:00 am8:00 am
April 12 (Sat)
11:30 pm11:30 pm
April 12 (Sat)
11:30 pm11:30 pm – April 12 (Sat)
Final biological analysis of Build 11.5 in AceDB conducted and completed draft genome assembly (29,736 bp) deposited online for download.
GROUP I
GROUP II
GROUP III
GROUP I
GROUP II
GROUP III
GROUP II GROUP III
Phylogenetic trees of protein sets with three other known coronaviral groups
Transcription Regulatory Sequences
Invited response to comment of Peng Shi et al.
On the quality of the Tor2 SARs-CoV genome sequence.
Marco A. Marra*, Jaswinder Khattra and Yaron S. N. Butterfield Canada’s Michael Smith Genome Sciences Centre
British Columbia Cancer Agency Vancouver, British Columbia
Canada V5Z 4E6 * To whom correspondence should be addressed.
Phone: 604-877-6084 FAX: 604-877-6085 Email: [email protected]
Marra MA, Jones SJM, Astell C, Holt RA, Brooks- Wilson AR, and 53 others. The Genome Sequence of the SARS-Associated Coronavirus. Sciencexpress 2003; 1126/science.1085953. In Press.
This publication describes the rapid generation of the complete and accurate sequence of the SARS- associated coronavirus. The Genome Sciences Centre generated and end-sequenced cDNAs, and then assembled these sequences into the final ~29 kilobase genome sequence. The entire effort took about six days, demonstrating that genome sequencing of a new viral pathogen could be considered a legitimate part of a "rapid response" to an emerging infectious disease.
Significance
• Clones distributed to academics and industry
• Stated purposes include expression of proteins (vaccines, neutralizing antibodies) and development of PCR and other diagnostic tools
What made it possible?
• The realization it should and could be done • The NML / BC CDC connection • Trained staff available • State-of-the-art equipment commissioned
and software installed
The initial and ongoing support from BCCA, GBC / GC, WD, NCI, NHGRI,…..
Special Challenges Development of new technologies continues apace, with the aim of increasing throughputs, decreasing operating costs and more sophisticated approaches and tools.
State of the art robotics and computers have a life span of ~2 years. A minimum requirement for maintenance of a nationally and internationally competitive research community requires an ongoing commitment to access and operate state of the art technologies.
Effective training of young genome researchers relies on the existence of established genomics research programs and platforms.
Retention of established researchers relies on their ability to conduct internationally competitive research.
Government and non-profit funding
CIHRNRCHRDCIndustry CanadaWED
BC BiotechKinexusKinetekXenonQLT
BC Cancer Agency
BC Cancer Agency Genome Sciences Centre
and