introduction to biological database

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Advanced Bioinformatics and Systems Biology 2008

Introduction to biological databaseIntroduction to biological database

Lecturer: Dr. Chih-Wen SunDept. of Life Sciences, NTNU

References:Molecular cell biology, 6th ed., Lodish et al. (2007)Various web resources

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Bioinformatics•Use or development of techniques (mathematics, informatics,

statistics, computer science, chemistry, biochemistry) to solvebiological problems

•Core principle: using computing tools and approaches toacquire, store, organize archive, analyze or visualizesequence/structure

•Major research efforts- Sequence alignment- Gene finding- Genome assembly- Protein structure alignment and prediction- Prediction of gene expression- Prediction of protein-protein interaction- Modeling of evolution

http://en.wikipedia.org/wiki/Bioinformatics

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Systems biology

•Quantitative and systematic study of complexinteraction in biological processes

•Biological systematics:- Study the diversity and relationship of lives on the

planet earth

http://en.wikipedia.org/wiki/systems_biology

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Strategies to determine the function,location, and structure of gene products

Molecular cell biology, 6th ed.Protein-protein interaction

Gene expression pattern

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Genomics: genome wide analysis ofgene structure and expression

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DNA sequencing by dideoxy method

Molecular cell biology, 6th ed.

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T C C A T G G A C CT C C A T G G A C

T C C A T G G A

T C C A T G G

T C C A T G

T C C A T

T C C A

T C C

T C

T

Electrophoresis gel

one of the manyfragments of DNAmigrating through the gel

CGCTTGACATCA

Detection of fluorescent signals


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•GenBank: National Center for Biotechnology Information(NCBI) server, National Institute of Health (NIH), Bethesda,Maryland, USA

•EMBL: European Bioinformatics Institute (EBI) server,European Molecular Biology laboratory, Heidelberg,Germany

•DDBJ: DNA Database of Japan, Mishima, Japan.

Three primary data banks

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Sequence comparison•BLAST program: basic local alignment search tool

- http://www.ncbi.nlm.nih.gov/BLAST/- BLAST algorithm divides the query sequence into shortersegments and then searches the database for significantmatches to any of the stored sequences

Paste or import the query sequence thatyou want to compare

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Motifs and domains•Motif: Short sequence segment on a protein that is functionally important•Domain: Region of a protein with a distinct tertiary structure and

characteristic activity•If a protein with no significant similarity to other proteins with the BLAST

algorithm, search for motif similarity might give clues


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Evolutionary relationship b/w genes•Protein family: related protein sequences•Gene family: corresponding genes of protein family•Gene homologs

- Orthologs- Paralogs

Phylogenic treeMolecular cell biology, 6th ed.

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Gene expression comparison•To monitoring the expression of few genes for organisms

during specific physiological responses or developmentalprocesses

•To monitoring the expression of thousands of genessimultaneously for organisms during specific physiologicalresponses or developmental processes

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DNA microarray•Probe sources:

•Fix ssDNA to glass slides or membranes

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DNA chip•Probe sources:

•Fix ssDNA to glass slides

www.carleton.ca/catalyst/2006s/hms7.html

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Microarray examples

Laser excitation

Cy5: ~650 nmCy3: ~550 nm

Image overlay

No changes

Flower genes

Leaves genesMolecular cell biology, 6th ed.

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Cluster analysis•Cluster analysis groups sets of genes which exhibit similar

expression changes or are co-regulated in a specific cellularprocess or pathway.

•This is very useful in analyzing microarray data

•Softwares:

Gene expression profile at time intervals over a 24h period after starved fibroblasts were providedwith serum: A) cholesterol biosynthesis, B) the cell cycle, C) the immediate-early response, D)signaling and angiogenesis, E) would healing and tissue remodeling


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Strategies to determine the function,location, and structure of gene products

Molecular cell biology, 6th ed.Protein-protein interaction

Gene expression pattern

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Proteomics: large-scale study ofprotein structures and functions

19NTNU-SUN Molecular cell biology, 6th ed.

Protein localization

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Determination of protein location•Wet experiments

•Dry experiments- ExPASy (Expert Protein Analysis System) server: Swiss

institute of Bioinformatics (SIB)

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ExPASy server

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24NTNU-SUN http://psort.ims.u-tokyo.ac.jp/

PSORT server

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Determination of protein function•Wet experiments

•Dry experiments- ExPASy (or InterPro)

- BLAST- Pfam (protein family)

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ExPASy server

27NTNU-SUNhttp://au.expasy.org/sprot/www.uniprot.org

Swiss-Prot server

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Prosite server


BLAST at ExPASy

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BLAST at NCBI

Paste or import the query sequence thatyou want to compare

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

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Pfam server

•Pfam is a large collection of multiple sequence alignmentsand hidden Markov models covering many common proteindomains and families. For each family in Pfam you can:- Look at multiple alignments- View protein domain architectures- Examine species distribution- Follow links to other databases- View known protein structures

http://pfam.sanger.ac.uk/

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Determination of protein structure•Wet experiments

•Dry experiments- ExPASy

- PDB (protein data bank) server

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PDB server

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Protein-protein interaction•Wet experiments

•Dry experiments- APID (Agile Protein Interaction DataAnalyzer) and APID2NET

(unified interactome graphic analyzer)- cons-PPISP (consensus neural-network Protein-Protein Interaction

Site Predictor)- InterPreTS (Interaction Prediction through Tertiary Structure)- InterProSurf (Prediction of functional sites in monomeric

protein surface)- PIP (Potential Interactions of Proteins)- PRISM (Protein interaction by structure matching)- SCOPPI (Structural Classification of Protein-Protein Interfaces)

http://en.wikipedia.org/wiki/Protein-protein_interaction_prediction

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Genome projects of variouseukaryotic organisms

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Assembled genome database at NCBI

http://blast.ncbi.nlm.nih.gov/Blast.cgi

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Example of animal genome projects

2006(2001)

Human Genome ProjectConsortium and Celera Genomics

250003.2 GbHuman

Homosapiens

2003Washington Univ., Sanger Inst.and Cold Spring Harbor Lab.

19500104 MbNematode

Caenorhabditisbriggsae]

2006Honeybee Genome SequencingConsortium

101571.8 GbHoneybee

Apismellifera

2002]International Fugu GenomeConsortium

22000-29000

390 MbPufferfish

Takifugurubripes]

2002International Collaboration for theMouse Genome Sequencing

241742.5 GbMouse]Musmusculus

2000Celera, UC Berkeley, EuropeanDGP, Baylor College of Medicine

13600165 MbFruitfly

Drosophilamelanogaster

Complete year

OrganizationGenes#

Genomesize

TypeOrganism

http://en.wikipedia.org/wiki/List_of_sequenced_eukaryotic_genomes

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Examples of plant genome projects

2008US Dept. of Energy Office ofScience Joint Genome Inst.

39458500 MbBryophyte

Physcomitrellapatens

2007The French-Italian PublicConsortium for GrapevineGenome Characterization

30434490 MbGrapevine

Vitis vinifera

2006The International PoplarGenome Consortium

45555550 MbPoplarPopulustrichocarpa

2004Univ. of Tokyo, Rikkyo Univ.,Saitama Univ., KumamotoUniv.

533116.5 MbRedalga

Cyanidioschyzon merolae

2002Syngenta and MyriadGenetics

46022-55615

466 MbRiceOryza sativassp japonica

2000Arabidopsis Genome Initiative27235125 MbCressArabidopsisthaliana

Completeyear

OrganizationGenes#

Genomesize

TypeOrganism

http://en.wikipedia.org/wiki/List_of_sequenced_eukaryotic_genomes

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Organism-specific genomeresources

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

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Organism-specific genomeresources

http://www.ncbi.nlm.nih.gov/projects/genome/guide/cat/http://www.ncbi.nlm.nih.gov/projects/genome/guide/dog/http://www.ncbi.nlm.nih.gov/projects/genome/guide/pig/

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http://www.ncbi.nlm.nih.gov/mapview/map_search.cgi?taxid=7227

Fly databases

http://flybase.bio.indiana.edu/

http://www.fruitfly.org/

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Examples of unigene identifier

•Am for honey bee•Bt for cow•Dm for fruitfly•Dr for zebrafish•Hs for human•Mm for mouse•Rn for mouse•Xl for frog

•At for Arabidopsis•Hv for barley•Os for rice•Ta for wheat•Zm for maize

Plants Animals

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General terms in GenBank•Accession number

- 1 letter + 5 digits (e.g., M12345)- 2 letters + 6 digits (e.g., AC123456)

•GenInfo identifier (GI)- 1 or more digits

•Protein ID- 3 letters + 5 digits (e.g., AAA35650)

•Version- M12345.1- M12345.2

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Refseq accession numbers

•NT_123456 constructed genomic contigs•NM_123456 mRNA•NP_123456 proteins•NC_123456 chromosomes•XM_123456 predicted mRNA•XP_123456 Predicted protein

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Exercises of biological databases

introduction to biological database

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