# Presentation: 062693

## Tools for Genome Analysis

- Peter FitzGerald, Ph. D.
- Genome Analysis Unit, NCI

- January 17, 2002 NCI/CIT Sponsored Talk

## Tools for Genome Analysis

- Status of Genome Projects
- Human, Mouse, and Others
- Types of Analysis
- Genome Browsers
- SNPs
- Cytogenetics
- Transcripts
- Promoters
- Transcription Factors
- Proteome
- GO Ontologies
- Comparative Genomics
- Additional Tools, Resources, and Information

## Tools for Genome AnalysisGenBank

-  GenBank® is the NIH genetic sequence database, an annotated collection of all publicly available DNA sequences. There are approximately 15,850,000,000 bases in 14,976,000 sequence records as of December 2001

## Tools for Genome AnalysisComplete Genomes

**Milestones** - **Complete Genome**
***First cellular organism****** ***
**Haemophilus influenzae  **	1.83 Mbp		Fleischmann et al., Science 269:496-512 (1995)
***First eukaryote organism***
**Saccharomyces cerevisiae **	13 Mbp		Goffeau et. al., Science 274: 563-567 (1996)
**Escherichia coli **		4.6 Mbp 		Blattner et. al., Science 277:1453-1474 (1997)
***First Multicellular organism***
**Caenorhabditis elegans **	97 Mbp		The C.Elegans Sequencing Consortium, Science
- 					282:2012-	2018 (1998)
**Drosophila melanogaster **	137 Mb 		Science 287:2185-2195 (2000)

## Tools for Genome AnalysisHuman Genome 2.9 Bbp (Feb 2001)

- International Human Genome
- Sequencing Consortium,
- Nature, 409: 860-921 (2001)

- Venter et. al. ,
-  Science 292:1304-1351 (2001)

## Tools for Genome AnalysisMouse 2.6 Bbp (April 2001)

**Celera Genomics**
**Spring/September 2001, unpublished**

## Tools for Genome AnalysisMouse 2.6 Bbp (Dec 2001)

**Mouse Genome Monthly December 2001 **
**The Latest Progress From the Mouse Genome Sequencing Consortium**
- 	>4.4x coverage (now ~6x coverage)
- 	Two assemblies
-  **Phusion**  - Sanger Institute
-  Arachne - Whitehead Institute
- 	November 9 freeze
- 		Both assemblies give over 90% coverage of the
- 		mouse genome at the contig level, and over 95%
- 		coverage at the ordered and oriented supercontig
- 		level.

## Tools for Genome AnalysisMouse 2.6 Bbp (Dec 2001)

- http://www.informatics.jax.org/mgihome/
- 	integrated access to data on the genetics, genomics, and biology of the laboratory mouse http://mouse.ensembl.org/
- 	The primary website of the Mouse Genome Sequencing Consortium
- http://www.ncbi.nlm.nih.gov/genome/guide/M_musculus.html
- 	mouse genome resources at the NCBI
- http://genome.uscc/
- 	 mouse genomic sequence reads aligned against the human draft sequence http://trace.ensembl.org/ and http://www.ncbi.nlm.nih.gov/Traces/trace.cgi?
- 	raw data
- http://www.nih.gov/science/models/
- 	information about NIH programs for analysis of model organisms
- http://mrcseq.har.mrc.ac.uk/
- 	the MRC UK Mouse Sequencing Programme

- http://rgd.mcw.edu/

## Tools for Genome AnalysisStatus of Human Genome Project

## Tools for Genome AnalysisStatus of Major Genome Projects

## Tools for Genome AnalysisStatus of Other Genome Projects

- _[GOLD[TM]: Genomes](http://wit.integratedgenomics.com/GOLD/)__[ OnLine](http://wit.integratedgenomics.com/GOLD/)__[ Database ](http://wit.integratedgenomics.com/GOLD/)__[HomePage](http://wit.integratedgenomics.com/GOLD/)_
- Published Complete Genomes: 	76
- Prokaryotic Ongoing Genomes:	260
- Eukaryotic Ongoing Genomes:	174
- _[NCBI](http://www.ncbi.nl.nih.gov/PMGifs/Genomes/org.html)_
- Completed: 72
- Eukaryota: 5
- Archaea: 11
- Bacteria: 56

## Tools for Genome AnalysisTypes of Analyses

- Genome Browsing
- Gene Finding
- Protein products
- Alternate splicing
- Transcription Control
- Single Nucleotide Polymorphysms (SNPs)
- Comparative Genomics
- Cytogenetics
- Expression Patterns

## Tools for Genome AnalysisGenome Browsers

## Tools for Genome Analysis Genome Browser Tools

-  Browsing
-  Image Maps
-  Java Viewers
-  Text Searching
- Various
-  Sequence Similarity Searching
- BLAST/MegaBLAST  (Basic Local Alignment Search Tool)
- BLAT (95% and greater similarity of length 40 bases or more)
- SSHA (Sequence Search and Alignment by Hashing Algorithm)

## Tools for Genome AnalysisBrowser Tools (UCSC)

- Base Position
- Chromosome Band
- STS Markers
- RH, YAC, and FISH maps.
- Mouse Synteny
- GC Percent
- FPC Contigs
- Assembly
- Gap
- Coverage
- Known Genes

-    Genie
-    Full mRNAs
-    Spliced ESTs
-    Human ESTs
-    CpG Islands
-    Exofish ecores.
-    RNA Genes
-    Overlap SNPs
-    Random SNPs
-    RepeatMasker
-    Simple Repeats

## Tools for Genome AnalysisRefSeq |ref|NM_000646.1| 

**What is a Reference Sequence? **The NCBI Reference Sequence project provides sequence data and related information for the community to use as a standard. Whereas GenBank is an archival repository of sequences, the RefSeq database is a non-redundant set of reference sequences, including constructed genomic contigs, mRNAs, proteins, and, in the future, entire chromosomes.
- Homo sapiens RefSeq records are provided by two methods:
- 1.	The Genome Assembly and Annotation process is a computational analysis pipeline that produces genomic contigs, and corresponding model mRNAs and proteins. [more...]
- 2.	The Curated RefSeq project supplies mRNA and protein sequence records for which a significant level of additional curation and review effort is provided. This FAQ is targetted toward the curated RefSeq data set. The curated RefSeq records are used (along with other sequence data) to define the model transcripts and proteins exported by the genome annotation process. [more...]
- 1.	PREDICTED - cDNA sequences of unknown function (automated)
- 2.	PROVISIONAL - annotation that was present on the source GenBank (automated)
- 3.	REVIEWED - manually processed by NCBI staff or collaborating groups
- 4.	GENOME ANNOTATION - automatic processing and include genomic contigs mRNAs, and proteins

## Tools for Genome AnalysisRefSeq vs GenBank 

**Format ****	****	****Molecule Type****	****	****Genome**** **
- NC_######	Complete Genome		Archaea Bacterial Organelle Virus Viroid
- 			Complete Chromosome	Eukaryote
- 			Complete Sequence		Plasmid
- NT_######	Genomic Contig	Homo sapiens
- NM_###### 	mRNA		Limited Vertebrate Homo sapiens Mus musculus
- 					Rattus norvegicus (Curated)
- NP_###### 	Protein 		All of the above (Curated)
- XM_###### 	mRNA 		Homo sapiens model transcripts provided by the Genome
- 					Annotation process; sequence corresponds to the genomic contig.
- XP_###### 	Protein 		Homo sapiens model proteins provided by the Genome
- 					Annotation process; sequence

## Tools for Genome AnalysisLocus Link & Unigene

- Locus Link provides a single query interface to curated sequence and descriptive information about genetic loci. It presents information on official nomenclature, aliases, sequence accessions, phenotypes, EC numbers, MIM numbers, UniGene clusters, homology, map locations, and related web sites.
- Sequence accessions include a subset of GenBank accessions for a locus, as well as a new type, the NCBI Reference Sequence (RefSeq). RefSeq records are built according to the process detailed here. See the About and FAQ pages for more information.
- Unigene UniGene is an experimental system for automatically partitioning GenBank sequences into a non-redundant set of gene-oriented clusters. Each UniGene cluster contains sequences that represent a unique gene, as well as related information such as the tissue types in which the gene has been expressed and map location.

## Tools for Genome AnalysisGenome Browsers

## Tools for Genome AnalysisSNPs

- _[SNP Consortium](http://snp.cshl.org/)_
- http://snp.cshl.org/
- _[SNPper](http://bio.chip.org:8080/bio/snpper-enter/)_
- http://bio.chip.org:8080/bio/snpper-enter/
- _[dbSNP](http://www.ncbi.nlm.nih.gov/SNP/)_
- http://www.ncbi.nlm.nih.gov/SNP/

## Tools for Genome AnalysisCytogenetic - FISH-mapped BACs 

- CGAP is generating a set of cytogenetically FISH-mapped BAC clones at a resolution of 1-2 MB across the human genome and have also been physically mapped to the genome based on STS data. The BAC clones have been linked to a parallel database of cancer-associated chromosome aberrations to provide a wealth of clinical, histopathologic and genetic information and to several relevant NCBI databases.
- _[http://](http://cgap.nci.nih.gov/Chromosomes/CCAP_BAC_Clones/)__[cgap](http://cgap.nci.nih.gov/Chromosomes/CCAP_BAC_Clones/)__[.](http://cgap.nci.nih.gov/Chromosomes/CCAP_BAC_Clones/)__[nci](http://cgap.nci.nih.gov/Chromosomes/CCAP_BAC_Clones/)__[.](http://cgap.nci.nih.gov/Chromosomes/CCAP_BAC_Clones/)__[nih](http://cgap.nci.nih.gov/Chromosomes/CCAP_BAC_Clones/)__[.](http://cgap.nci.nih.gov/Chromosomes/CCAP_BAC_Clones/)__[gov](http://cgap.nci.nih.gov/Chromosomes/CCAP_BAC_Clones/)__[/Chromosomes/CCAP_BAC_Clones/](http://cgap.nci.nih.gov/Chromosomes/CCAP_BAC_Clones/)_

## Tools for Genome Analysis Full Length Transcripts

- http://elmo.ims.u-tokyo.ac.jp/dbtss/

-  http://mgc.nci.nih.gov/index_html/

- http://www.allgenes.org/

## Tools for Genome AnalysisPromoters

- _[WWW Promoter Scan](http://bimas.cit.nih.gov/molbio/proscan/)_
- http://bimas.cit.nih.gov/molbio/proscan/

- http://genomatix.gsf.de/cgi-bin/promoterinspector/promoterinspector.pl

- http://www.epd.isb-sib.ch/

- http://www.cbs.dtu.dk/services/promoter/

## Tools for Genome AnalysisTranscription Factors

- http://www.ifti.org/

- _[TESS](http://www.cbil.upenn.edu/tess/)_

- http://www.cbil.upenn.edu/tess/

- http://transfac.gbf.de/TRANSFAC/

## Tools for Genome AnalysisProteins

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

## Tools for Genome AnalysisGene Ontology (GO) http://www.geneontology.org/

- _[The Gene Ontology](http://www.geneonotology.org/)_ (GO) Consortium is developing a dynamic controlled vocabulary that can be used to annotate all eukaryotic genes.
- 	The GO vocabulary has a hierarchical structure that permits a range of detail from high-level, broadly descriptive terms to very low-level, highly specific terms. The complete vocabulary is structured into three broad categories, reflecting the biological roles of genes:
- Molecular Function - tasks performed by individual gene products
- Biological Process - broad biological goals accomplished by ordered assemblies of molecular functions
- Cellular Component - subcellular structures, locations, and macromolecular complexes
- GOBrowser http://cgap.nci.nih.gov/Genes/GOBrowser
- TIGR Gene Index http://www.tigr.org/tdb/tgi.shtml

## Tools for Genome AnalysisComparative Genomics

- http://www-gsd.lbl.gov/vista/

- http://pipeline.lbl.gov/

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

## Tools for Genome AnalysisComparative Genomics

## Tools for Genome AnalysisAdditional Tools

**Sequence Analysis (Web Based)**
- _[ NCBI](http://www.ncbi.nlm.nih.gov/)_
- _[ Computational Molecular Biology at NIH](http://molbio.info.nih.gov/)_
- _[ SeqWeb](http://seqweb.nih.gov/)_
- _[ GCG-](http://molbio.info.nih.gov/gcglite/)__[Lite](http://molbio.info.nih.gov/gcglite/)_
- _[ ABCC (Frederick)](http://www22.ncifcrf.gov/app/html/SeqAnaly/)__ _
-  _[Helix Systems](http://helix.nih.gov/)_
-  GCG
-  EMBOSS

**High Volume Sequence Analysis**
** ****NIH**_[ ](http://www.biowulf.nih.gov/)__[Biowulf ](http://www.biowulf.nih.gov/)_
-  Blast
-  NCBI Sequence databases
-  NCBI Human Genome Assembly
-  BLAT
-  _UCSC April 2001 build_
- _ __UCSC Aug 2001_
- _ __Dec 2001 build _

*GRAIL PipeLine*
*http://compbio.ornl.gov/GP3/*

*FuzzyFinder*
*http://genome.nci.nih.gov/tools/fuzzyFind.html*

## Tools for Genome AnalysisAdditional Resources

- Nucleic Acid Research  **Volume 30, Number 1**   January 1 2002
- _[http://](http://nar.oupjourlans.org/contents/vol30/issue1/index.shtml)__[nar](http://nar.oupjourlans.org/contents/vol30/issue1/index.shtml)__[.](http://nar.oupjourlans.org/contents/vol30/issue1/index.shtml)__[oupjournals](http://nar.oupjourlans.org/contents/vol30/issue1/index.shtml)__[.org/content/vol30/issue1/index.](http://nar.oupjourlans.org/contents/vol30/issue1/index.shtml)__[shtml](http://nar.oupjourlans.org/contents/vol30/issue1/index.shtml)_
- _[http://www3.](http://www3.oup.co.uk/nar/database/)__[oup](http://www3.oup.co.uk/nar/database/)__[.co.](http://www3.oup.co.uk/nar/database/)__[uk](http://www3.oup.co.uk/nar/database/)__[/](http://www3.oup.co.uk/nar/database/)__[nar](http://www3.oup.co.uk/nar/database/)__[/database/](http://www3.oup.co.uk/nar/database/)_

- http://restools.sdsc.edu/

## Tools for Genome AnalysisAdditional Classes

- http://www.nhgri.nih.gov/COURSE2002/

- http://training.cit.nih.gov/

- High Volume High Speed Sequence Analysis on the Biowulf Supercluster

## Tools for Genome AnalysisAdditional Info

- http://genome.nci.nih.gov/

- http://genome.nci.nih.gov/talks/genome_tools/