Presentation is loading. Please wait.

Presentation is loading. Please wait.

Computational Molecular Biology Biochem 218 – BioMedical Informatics 231 Doug Brutlag Professor.

Published byEverett Gibson Modified over 8 years ago

Similar presentations

Presentation on theme: "Computational Molecular Biology Biochem 218 – BioMedical Informatics 231 Doug Brutlag Professor."— Presentation transcript:

1 Computational Molecular Biology Biochem 218 – BioMedical Informatics 231 http://biochem218.stanford.edu/ http://biochem218.stanford.edu/ Doug Brutlag Professor Emeritus Biochemistry & Medicine (by courtesy) The Human Genome Project

2 Maeve’s Office Hours Monday and Friday 3:30 to 5:00 PM Beckman Center B403A Please Email Maeve to set up an appointment if you want to meet with her. –maeveo@stanford.edumaeveo@stanford.edu Take the elevator to the fourth floor of Beckman and turn left. The hallway leads directly to the lab B403 and my office is inside the lab at B403A.

3 Current Topics in Genome Analysis 2010 http://www.genome.gov/12514288 http://www.genome.gov/12514288

4 Hierarchical Sequencing vs. Whole Genome Shotgun Sequencing © Gibson & Muse A Primer of Genome Science from Gibson & Muse, A Primer of Genome Science http://www.sinauer.com/genomics/

5 The Human Genome Project: How should we do it? Weber, J. L., & Myers, E. W. (1997). Human whole-genome shotgun sequencing. Genome Res, 7(5), 401-409.Weber, J. L., & Myers, E. W. (1997). Human whole-genome shotgun sequencing. Genome Res, 7(5), 401-409. –http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation& list_uids= 9149936http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation& list_uids= 9149936 –Use multiple length clones 2 kb, 10 kb and 50 kb –Use clone end sequencing generating mate-pairs –Able to use long clones to leap over repeated regions –Clone length permits one to measure length of repeated regions. –Will find more polymorphisms (SNPs) –Costs less –BAC clone artifacts Differential amplification BACs not stable in bacteria will be lost. Repeated regions will recombine and be lost Green, P. (1997). Against a whole-genome shotgun. Genome Res, 7(5), 410-417.Green, P. (1997). Against a whole-genome shotgun. Genome Res, 7(5), 410-417. –http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation& list_uids=9149937http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation& list_uids=9149937 –Preferred clone-by-clone BAC sequencing –Distributed versus monolithic organization –BACs linked to genetic maps –Costs less (sequence 4x human genome) –Finishing simplified and fewer gaps –Haplotyping automatic –Longer repeat regions lengths measured

6 Gene Myers Let’s sequence the human genome with the shotgun strategy That is impossible, and a bad idea anyway Phil Green 1997 History of Whole Genome Assembly Thanks to Serafim Batzoglou

7 Public Human Genome Project Strategy http://www.genome.gov/ http://www.genome.gov/

8 Contig Formation as Mapping Progresses Lander & Waterman 1988 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=3294162 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=3294162

9 Public Genome Assembly Process

10 BAC and PAC Libraries in Public Human Genome Project http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_ uids=11237011 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_ uids=11237011

11 Total Genome Sequence Information 2001 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11237011 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11237011

12 Comparing Chromosome 2 Sequence Versus Genetic Maps http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11237011 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11237011

13 Synteny Between Human and Mouse http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=11237011 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db =PubMed&dopt=Citation&list_uids=11237011

14 Celera Sequencing http://www.celera.com/ http://www.celera.com/

15 Celera Scaffolds http://www.sciencemag.org/cgi/content/full/291/5507/1304 http://www.sciencemag.org/cgi/content/full/291/5507/1304

16 Celera Assembler

17 Chromosome 21: Public vs Celera Assemblies http://www.sciencemag.org/cgi/content/full/291/5507/1304 http://www.sciencemag.org/cgi/content/full/291/5507/1304

18 Chromosome 8: Public vs. Celera http://www.sciencemag.org/cgi/content/full/291/5507/1304 http://www.sciencemag.org/cgi/content/full/291/5507/1304

19 Finishing Strategy for the Public Genome Project http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&d opt=Citation&list_uids=15496913

20 Finished Sequence in 2004 (Build 35) http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15496913 http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15496913

21 Chromosome 7: Draft versus Finished Sequence http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&dopt=Citation&list_ui ds=15496913 http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&dopt=Citation&list_ui ds=15496913

22 Substitutions in BAC Overlaps with BACs from Same or Different Libraries

23 Gaps in BAC Overlaps with BACs from Same or Different Libraries

24 Duplications and Deletions in the Human Genome

25 Percentage of Chromosomes Duplicated http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&dopt=Citatio n&list_uids=15496913 http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&dopt=Citatio n&list_uids=15496913

26 Available Next Generation Sequencing Technologies Illumina – Solexa –http://www.illumina.com/http://www.illumina.com/ Illumina Technology –http://www.illumina.com/technology/sequencing_technology.ilmnhttp://www.illumina.com/technology/sequencing_technology.ilmn 454 Life Sciences –http://www.454.com/http://www.454.com/ 454 Life Sciences Technology –http://www.454.com/products-solutions/how-it-works/index.asphttp://www.454.com/products-solutions/how-it-works/index.asp Applied Biosystems Inc. (ABI) SOLID Sequencing –http://solid.appliedbiosystems.com/http://solid.appliedbiosystems.com ABI SOLID Sequencing Technology –http://www3.appliedbiosystems.com/AB_Home/applicationstechnologies/ SOLiDSystemSequencing/OverviewofSOLiDSequencingChemistry/index. htmhttp://www3.appliedbiosystems.com/AB_Home/applicationstechnologies/ SOLiDSystemSequencing/OverviewofSOLiDSequencingChemistry/index. htm

27 Next Generation Sequencing Technologies in Development Pacific BioSciences –http://www.pacificbiosciences.com/http://www.pacificbiosciences.com/ Pacific BioSciences Technology –http://www.pacificbiosciences.com/index.php?q=technology-introductionhttp://www.pacificbiosciences.com/index.php?q=technology-introduction Helicos –http://www.helicosbio.com/http://www.helicosbio.com/ Helicos Technology –http://www.helicosbio.com/Technology/TrueSingleMoleculeSequencing/ta bid/64/Default.aspxhttp://www.helicosbio.com/Technology/TrueSingleMoleculeSequencing/ta bid/64/Default.aspx Complete Genomics –http://www.completegenomics.com/http://www.completegenomics.com Complete Genomics Technology –http://www.completegenomics.com/technology /technicalDetails.aspxhttp://www.completegenomics.com/technology /technicalDetails.aspx

Download ppt "Computational Molecular Biology Biochem 218 – BioMedical Informatics 231 Doug Brutlag Professor."

Similar presentations

The Human Genome Project Main reference: Nature (2001) 409, 860-921

The Human Genome Project Main reference: Nature (2001) 409,
Celera Assembler Arthur L. Delcher Senior Research Scientist CBCB University of Maryland.

Celera Assembler Arthur L. Delcher Senior Research Scientist CBCB University of Maryland.
Sequencing a genome. Definition Determining the identity and order of nucleotides in the genetic material – usually DNA, sometimes RNA, of an organism.

Sequencing a genome. Definition Determining the identity and order of nucleotides in the genetic material – usually DNA, sometimes RNA, of an organism.
Doug Brutlag 2011 Sequencing the Human Genome Doug Brutlag Professor Emeritus of Biochemistry.

Doug Brutlag 2011 Sequencing the Human Genome Doug Brutlag Professor Emeritus of Biochemistry.
The IWGSC: Building the sequence-based foundation for accelerated wheat breeding Kellye A. Eversole IWGSC Executive Director & The IWGSC Cereals for Food,

The IWGSC: Building the sequence-based foundation for accelerated wheat breeding Kellye A. Eversole IWGSC Executive Director & The IWGSC Cereals for Food,
SEQUENCING-related topics 1. chain-termination sequencing 2. the polymerase chain reaction (PCR) 3. cycle sequencing 4. large scale sequencing stefanie.hartmann.

SEQUENCING-related topics 1. chain-termination sequencing 2. the polymerase chain reaction (PCR) 3. cycle sequencing 4. large scale sequencing stefanie.hartmann.
CS273a Lecture 5, Win07, Batzoglou Quality of assemblies—mouse N50 contig length Terminology: N50 contig length If we sort contigs from largest to smallest,

CS273a Lecture 5, Win07, Batzoglou Quality of assemblies—mouse N50 contig length Terminology: N50 contig length If we sort contigs from largest to smallest,
CS273a Lecture 4, Autumn 08, Batzoglou Some Terminology insert a fragment that was incorporated in a circular genome, and can be copied (cloned) vector.

CS273a Lecture 4, Autumn 08, Batzoglou Some Terminology insert a fragment that was incorporated in a circular genome, and can be copied (cloned) vector.
DNA Sequencing Lecture 9, Tuesday April 29, 2003.

DNA Sequencing Lecture 9, Tuesday April 29, 2003.
DNA Sequencing. The Walking Method 1.Build a very redundant library of BACs with sequenced clone- ends (cheap to build) 2.Sequence some “seed” clones.

DNA Sequencing. The Walking Method 1.Build a very redundant library of BACs with sequenced clone- ends (cheap to build) 2.Sequence some “seed” clones.
Mining SNPs from EST Databases Picoult-Newberg et al. (1999)

Mining SNPs from EST Databases Picoult-Newberg et al. (1999)
DNA Sequencing. CS273a Lecture 3, Spring 07, Batzoglou DNA sequencing How we obtain the sequence of nucleotides of a species …ACGTGACTGAGGACCGTG CGACTGAGACTGACTGGGT.

DNA Sequencing. CS273a Lecture 3, Spring 07, Batzoglou DNA sequencing How we obtain the sequence of nucleotides of a species …ACGTGACTGAGGACCGTG CGACTGAGACTGACTGGGT.
Stuff to Do. Midterm I questions due 1/31 Email me your question (with answers), –if you have the capability, mail complete questions, figures, etc. and.

Stuff to Do. Midterm I questions due 1/31 me your question (with answers), –if you have the capability, mail complete questions, figures, etc. and.
CS273a Lecture 9, Aut08, Batzoglou CS273a Lecture 9, Fall 2008 Quality of assemblies—mouse N50 contig length Terminology: N50 contig length If we sort.

CS273a Lecture 9, Aut08, Batzoglou CS273a Lecture 9, Fall 2008 Quality of assemblies—mouse N50 contig length Terminology: N50 contig length If we sort.
Sequencing Informatics Gabor T. Marth Department of Biology, Boston College BI420 – Introduction to Bioinformatics.

Sequencing Informatics Gabor T. Marth Department of Biology, Boston College BI420 – Introduction to Bioinformatics.
Sequencing and Assembly Cont’d. CS273a Lecture 5, Win07, Batzoglou Steps to Assemble a Genome 1. Find overlapping reads 4. Derive consensus sequence..ACGATTACAATAGGTT..

Sequencing and Assembly Cont’d. CS273a Lecture 5, Win07, Batzoglou Steps to Assemble a Genome 1. Find overlapping reads 4. Derive consensus sequence..ACGATTACAATAGGTT..
Sequencing and Assembly Cont’d. CS273a Lecture 5, Aut08, Batzoglou Steps to Assemble a Genome 1. Find overlapping reads 4. Derive consensus sequence..ACGATTACAATAGGTT..

Sequencing and Assembly Cont’d. CS273a Lecture 5, Aut08, Batzoglou Steps to Assemble a Genome 1. Find overlapping reads 4. Derive consensus sequence..ACGATTACAATAGGTT..
Sequencing Informatics Gabor T. Marth Department of Biology, Boston College BI420 – Introduction to Bioinformatics.

Sequencing Informatics Gabor T. Marth Department of Biology, Boston College BI420 – Introduction to Bioinformatics.
CS273a Lecture 4, Autumn 08, Batzoglou Hierarchical Sequencing.

CS273a Lecture 4, Autumn 08, Batzoglou Hierarchical Sequencing.
DNA Sequencing and Assembly. DNA sequencing How we obtain the sequence of nucleotides of a species …ACGTGACTGAGGACCGTG CGACTGAGACTGACTGGGT CTAGCTAGACTACGTTTTA.

DNA Sequencing and Assembly. DNA sequencing How we obtain the sequence of nucleotides of a species …ACGTGACTGAGGACCGTG CGACTGAGACTGACTGGGT CTAGCTAGACTACGTTTTA.

Similar presentations

Ads by Google