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INTRODUCTION TO BIOLOGICAL DATABASES

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Page 1: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

INTRODUCTION TO BIOLOGICAL DATABASES

Page 2: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

Basic Genomic Characteristic AIM: to collect as much general

information as possible about your gene:Nucleotide sequence Databases

○ NCBI GenBank○ EMBL Nucleotide Sequence Database○ DDBJ

For Protein sequences○ UniProtKB

NCBI Reference Sequence (RefSeq)

Page 3: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

Nucleotide sequence DB

The 3 databases form an international collaboration. Each of the three groups collects a portion of the total sequence data reported worldwide, and all new and updated database entries are exchanged between the groups on a daily basis.

You do not need to check all of them!

Page 4: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

Nucleotide sequence DB

Page 5: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

Nucleotide sequence DB

Page 6: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

Nucleotide sequence DB

Page 7: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

Nucleotide sequence DB

Page 8: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

Nucleotide sequence DB

Page 9: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

NCBI Entrez

Present all the information available at NCBI for a gene. Entrez is a integrated searching tool across all the databases

Page 10: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

Genome Browsers

NCBI Sequence Viewer

UCSC Genome Browser

ENSEMBL

Page 11: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

NCBI Sequence Viewer

This is an example view of the human beta globin region on chr11

Page 12: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

UCSC Genome Browser

Page 13: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

ENSEMBL

Page 14: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

ENSEMBL – genome view

Page 15: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

ENSEMBL – Gene tree

Page 16: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

NCBI OMIM database

Nucleotide databases and Genome Browser provide information on the gene nucleotide sequence (exon, intron, alternative splicing sites…) but give you very few information on gene function

OMIM database provide a summary of all the literature concerning a gene.

Page 17: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

NCBI OMIM database

Page 18: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

Protein Databases

Protein databases provide useful information about the function of gene: e.g. conserved protein domains,…

UniProt is the reference database Interpro offer automatic protein

annotation based on conserved domains RefSeq

Page 19: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

Protein databases - UniProt

Page 20: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

Protein databases - UniProt

Page 21: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

Protein databases - UniProt

Page 22: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

Protein databases - UniProt

Page 23: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

Similarity search

If your gene has no protein information

Protein sequence availableBLASTP against a non redundant protein

database

Protein sequence unavailableBLASTX against a non redundant protein

database

Page 24: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

Protein 3D structure

Many proteins have the 3D structure determined. Biggest databases are:PDBNCBI Structure GroupDali

They offer tools for the visualization

Page 25: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

PDB database

The visualization tools allows you to see the structure and the ligands (if presents), rotate the image and zoom-in

Page 26: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

3D structure prediction

Structure still available for a limited number of proteins

Effort to predict protein structures based on sequences similarities

Still not very accurate!

SwissModel PSIPRED PredictProtein

Page 27: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

Swiss-Model

Page 28: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

Protein interaction databases AIM: find proteins that interact with your

target

IntAct: EBI resource to find interctors

BioGRID: is a freely available interaction database from model organisms and humans.

Page 29: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

IntAct

Page 30: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

Regulatory and metabolic pathways

the classic “KEGG”:

Page 31: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

miRNA specific resources Databases:

miRNAMap: it present several useful information such as secondary structure, tissue specific expression and predicted target gene

HMDD: is specific for disease-miRNA associationMiRbase: is a searchable database of published

miRNA sequences and annotation. Target Prediction tools:

miRecords: is a good repository that shows confirmed target genes and predictions from several other software

Page 32: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

C. Elegans specific tools

WormBase: is the main resource of information on C. elegans.

Expression pattern databaseHope lab Expression Pattern Database The Nematode Expression Pattern

DataBase Caenorhabditis elegans Genetics and

Genomics: provides links to many useful resources for C. elegans

Page 33: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

Expression databases

Allows exploratory analyses of multiple experiments

Experiments need to be linked Require much information about how

experiments where conducted = sources of variation

Very different to genomic databases MIAME standard

Page 34: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

MIAME

Experimental design Microarray design Extraction, preparation and labelling Hybridisation conditions Measurements: images, quantifications,

parameters Systematic error adjustments and

transformations

Page 35: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

MIAME

Page 36: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

Gene Expression Omnibus NCBI administered ~280,000 samples >100 organisms >1,000,000,000

measurements

Page 37: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

Gene Expression Omnibus

Page 38: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

Gene Expression Omnibus

Page 39: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

Gene Expression Omnibus

Page 40: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

Gene Expression Omnibus

Page 41: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

Gene Expression Omnibus

Page 42: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

ArrayExpress

EBI administered >7000 experiments Provide p-values Bioconductor

package

Page 43: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

ArrayExpress

Page 44: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

ArrayExpress

Page 45: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

ArrayExpress

Page 46: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

ArrayExpress

Page 47: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

ArrayExpress

Page 48: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

GEO and ArrayExpress Databases provide:

The raw data for each hybridization (e.g., CEL or GPR files) The final processed (normalized) data for the set of hybridizations in the

experiment (study) (e.g., the gene expression data matrix used to draw the conclusions from the study)

The essential sample annotation including experimental factors and their values (e.g., compound and dose in a dose response experiment)

The experimental design including sample data relationships (e.g., which raw data file relates to which sample, which hybridizations are technical, which are biological replicates)

Sufficient annotation of the array (e.g., gene identifiers, genomic coordinates, probe oligonucleotide sequences or reference commercial array catalog number)

The essential laboratory and data processing protocols (e.g., what normalization method has been used to obtain the final processed data)

Page 49: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

Problems:

Difficult compare experiments Significant genes not highlighted Poor results visualization

ArrayExpress is trying with its Atlas to solve this problems

Page 50: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

Genevestigator

It is JAVA visualization tool that summarizes results from thousands of high quality transcriptomic experiments

Much easier to compare samples

Open access to only some of the data and 1 probeset/gene

Page 51: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

Genevestigator

Page 52: Basic Genomic Characteristic  AIM: to collect as much general information as possible about your gene: Nucleotide sequence Databases ○ NCBI GenBank ○

ONCOMINE