Bioinformatic Databases

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Bioinformatic Databases

• Norie de la Cruz, PhD

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Take home

• The internet is a powerful resource containing a
  large volume of data and tools to manipulate
  them unfortunately, connecting data between them
  can sometimes be tricky.

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Overview

• Whirlwind tour of Web databases
• The Rat Genome Database data, tools, and
  operations

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Bioinformatic databases on the WWW

• Loose definition of database here
• Vary widely in terms of offerings, data, tools
  and specialization
• Vary widely in terms of data collection
  methodologies

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Some classifications per NAR

• Major sequence repositories
• Gene Expression
• Comparative genomics
• Gene Identification and Structure
• Genetic and physical maps
• Genomic Databases
• Intermolecular interactions
• Metabolic Pathways and Cellular Regulation
• Mutation Databases
• Pathology

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Some classifications per NAR

• Protein Databases
• Protein sequence Motifs
• Proteome Resources
• Retrieval systems
• RNA Sequences
• Structure
• Transgenics
• Varied Biomedical Content

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Major Sequence Repositories

• GenBank
• RefSeq
• DDBJ
• Ensemble
• Unigene

• Collection of sequence data
• Genomic
• Markers
• Genes
• Proteins
• Some provide tools to expedite access
• Blast Search
• Alignment tools
• Translation tools etc.
• Varying degrees of quality control
• Machine data upload
• Human curation and QC

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Major Sequence Repositories Genbank

• All know nucleotide and protein sequences
• Provides submission system for various authors
• Little QC

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Major Sequence Repositories RefSeq

• Non redundant collection of naturally occurring
  biological molecules
• Human QC
• Comprehensive, integrated set of sequences for
  major research organisms
• Provides a stable reference for further
  characterization of sequences including
  comparative analyses, mutations, expression, etc.

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Major Sequence Repositories Unigene

• Attempts to cluster GenBank sequences into
  gene-oriented clusters
• Each cluster contains sequences that represent
  one gene
• Provides a stable reference for further
  characterization of sequences including
  comparative analyses, mutations, expression, etc.

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Major Sequence Repositories DDBJ (DNA Data Bank
of Japan)

• Japanese equivalent to NCBI efforts
• Attempting to gather all known nucleotide and
  protein sequences
• Part of the International Nucleotide Sequence
  Collaboration

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Major Sequence Repositories EMBL Nucleotide
Sequence Database

• European equivalent to NCBI efforts
• Attempting to gather all known nucleotide and
  protein sequences
• Part of the International Nucleotide Sequence
  Collaboration

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Major Sequence Repositories UCSC Genome Browser

• Visual representation of genome and sequence data
• Run by University of California at Santa Cruz

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Comparative Genomics

• Examines the similarities and difference in
  Genome organization
• Clustering of like data across multiple genomes
  protein motifs
• Cross referencing of genome data across genomes

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Comparative Genomics Microbial Genome Database
for Comparative Analysis

• MBGD is a database for comparative analysis of
  completely sequenced microbial genomes
• MBGD aims to facilitate comparative genomics from
  various points of view such as ortholog
  identification, paralog clustering, motif
  analysis and gene order comparison

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Comparative Genomics Some specialized sites

• Homophila human diseases and Drosophila gene
  relationships
• CORG conserved non coding sequence blocks
• ParaDB paralog mapping in human genomes

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Comparative Genomics Clusters of Orthologous
Groups

• Phylogenetic classification of the proteins
  encoded in complete genomes
• Proteins grouped according to sequence by a
  program called COGNITOR
• Must be represented in at least three species in
  a group of 43 species representing phylogenetic
  lineages
• Each COG consists of individual proteins or
  groups of paralogs from at least 3 lineages and
  thus corresponds to an ancient conserved domain.

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Gene Expression

• Analysis of gene expression patterns
• Repositories of microarray data
• Analysis of tissue specificities of gene
  expression
• Analysis of expression patterns for genes linked
  to specific diseases
• Analysis of gene expression regulatory networks

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Gene Expression Array Express

• ArrayExpress is a new public database of
  microarray gene expression data at the EBI
• The ArrayExpress infrastructure consists of
• the database itself,
• data submissions in MAGE-ML format or via an
  online submission tool MIAMExpress,
• online database query interface, and the
• Expression Profiler online analysis tool.

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Gene Expression Edinburgh Mouse Atlas Project

• database to be a resource for spatially mapped
  data such as in situ gene expression and cell
  lineage
• The gene expression database (emage) is being
  developed as part of the Mouse Gene Expression
  Information Resource (MGEIR) in collaboration
  with the Jackson Laboratory, USA

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Gene Expression HugeIndex (Human Gene Expression
Index)

• aims to provide a comprehensive database to
  understand the expression of human genes in
  normal human tissues
• mRNA expression levels of thousands of genes are
  obtained using high-density oligonucleotide array
  technology and used to create a public
  database.

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Gene Expression Other specialized sites

• Kidney development database
• TRIPLES Transposon-insertion phenotypes,
  localization and expression in Saccharomyces
• Tooth Development database
• MethDB DNA methylation data, patterns and
  profile

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Gene Identification and Structure

• Focuses on the analysis of sequences to determine
  gene structures
• Analysis of gene expression control signals
• Analysis of coding signals
• Analysis of variations in the exons alleles
• Analysis of codon usage

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Gene Identification and StructureSNP Consortium
database

• collaboration that has to date discovered and
  characterized nearly 1.8 million SNPs
• Now that the SNP discovery phase of the TSC
  project is essentially complete, the emphasis has
  shifted to studying SNPs in populations

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Gene Identification and StructureAlternative
Splicing Annotation Project (ASAP)

• for biologists to access and mine the enormous
  wealth of alternative splicing information coming
  from genomics and proteomics
• use the UniGene clusters of human Expressed
  Sequence Tags (ESTs) to identify splices

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Gene Identification and StructurePromEC

• Database of promoters of characterized genes in
  E. coli

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Gene Identification and StructureSome other
specialized sites

• Place Plant cis acting regulatory elements
• Sputnik Functional annotation of clustered
  plant ESTs
• VIDA Virus Open reading frames
• HS3D Human exon, intron, splice regions

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Genetic and physical maps

• Repository for marker information
• Data on gene locations within the genome
• Map of cloned sequences
• Tools to integrate information across genomes

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Genetic and Physical MapsHuGeMap

• Collections of human genetic maps from Genethon
  and the Coorperative Human Linkage Center
• Collections of physical maps from Genethon and
  the Whitehead Institute

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Genetic and Physical MapsGeneMap99

• A map of 30,181 human gene-based markers was
  assembled and integrated with the current genetic
  map by radiation hybrid mapping.
• constitutes an important infrastructure and tool
  for the study of complex genetic traits, the
  positional cloning of disease genes, the
  cross-referencing of mammalian genomes, and
  validated human transcribed sequences for
  large-scale studies of gene expression

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Genomic Databases

• Data repositories for research results on various
  model organisms
• Rat
• Human
• Fruit fly
• Worm
• Arabidopsis
• Some other rodent
• Linking information across databases
• Tools to organize and integrate information

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Genomic DatabasesThe Rat Genome Database

• Consolidates and integrates Rat research data
• Presents data on genes, qtls, sslps,ests etc.
• Fields a series of tools to help analysis and
  integration with data within and without.

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Genomic DatabasesFlyBase

• Focuses on Drophila genome data
• Presents data on genes, stocks, ests,
  transposons, sequences.
• Not a lot of tools

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Genomic DatabasesEcoGene

• EcoGene is a collection of information about the
  genes, proteins, and intergenic regions of the E.
  coli K-12 genome and proteome
• Collaborative effort between many laboratories

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Genomic DatabasesSome other examples

• wormbase C. elegans
• oryzabase rice
• TAIR Arabidopsis
• IRIS Rice germplasm
• MitoDat Mitochondrial proteins
• MGI Medicago
• CropNet crop plants
• MGD another rodent

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Mutation Databases

• Allele distributions in populations
• Inherited genetics diseases
• Mutations in proteins implicated in disease
  development

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Mutation Databases ALFRED

• designed to make allele frequency data on
  anthropologically defined human population
  samples readily available to the scientific
  community
• link these polymorphism data to the molecular
  genetics-human genome databases

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Mutation Databases Human Gene Mutation Database

• an attempt to collate known (published) gene
  lesions responsible for human inherited disease
• provides information of practical diagnostic
  importance to
• researchers and diagnosticians in human molecular
  genetics
• physicians interested in a particular inherited
  condition in a given patient or family
• genetic counsellors.

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Mutation DatabasesOnline Mendelian Inheritance
in Man (OMIM)

• catalog of human genes and genetic disorders
• contains textual information, pictures, and
  reference information

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Mutation Databases Other examples

• Atlas of Genetics and Cytogenetics in Oncology
  and Haematology
• Database of Germline p53 Mutations
• SV40 Large T-Antigen Mutant Database
• KinMutBase Disease causing kinase mutations

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Protein Databases

• Protein sequences collection
• Clustering of protein data into families
• Specialized protein sites
• Organism
• Function
• Large variety of enzymes

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Protein Databases InterPro

• a database of protein families, domains and
  functional sites in which identifiable features
  found in known proteins can be applied to unknown
  protein sequences
• amalgamating the major protein signature
  databases, data have been manually integrated and
  curated and are available in InterPro
• PROSITE
• Pfam
• PRINTS
• ProDom
• SMART
• TIGRFAMs

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Protein DatabasesProtoNet

• provides global classification of the proteins,
  from the SWISS-PROT database into hierarchical
  clusters
• clustering is based on an all-against-all BLAST
  similarity search

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Protein DatabasesiProClass

• an integrated resource that provides
  comprehensive family relationships and
  structural/functional features of proteins
• currently consists of non-redundant PIR and
  SwissProt/TrEMBL proteins
• 36,200 PIR superfamilies
• 145,300 families
• 5720 domains
• 1300 motifs
• 280 post-translational modification sites
• links to over 50 biological databases.

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Protein Databases Other Examples

• Nuclear Protein Database Proteins localized in
  the nucleus
• PLANT-Pls Plant protease inhibitors
• SWISS-PROT/TrEMBL Curated protein sequences
• SENTRA Sensory signal transduction proteins
• Ribonuclease P Database

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Protein Sequence Motifs

• Alignment of protein sequences
• Organization of proteins into families

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Protein Sequence MotifsBLOCKS

• multiply aligned ungapped segments corresponding
  to the most highly conserved regions of proteins
• Tools
• Block Searcher -- compare a protein or DNA
  sequence to a database of protein blocks
• Get Blocks -- retrieve blocks
• Block Maker -- create new blocks

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Protein Sequence MotifsPfam

• a large collection of multiple sequence
  alignments and hidden Markov models covering many
  common protein domains 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

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Protein Sequence MotifsPROSITE

• database of protein families and domains. It
  consists of biologically characterized sites,
  patterns and profiles that help to reliably
  identify to which known protein family (if any) a
  new sequence belongs
• currently contains patterns and profiles specific
  for more than a thousand protein families or
  domains.
• each of these signatures comes with documentation
  providing background information on the structure
  and function of these proteins

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Protein Sequence Motifs Other Examples

• ASC Active Sequence Collection Biologically
  active oligopeptides
• ClusTr Automatic classification of SWISS-PROT
  and TrEMBL proteins
• TMPDB Experimentally-characterized
  transmembrane topology
• O-GLYCBASE O- and C- linked glycosylation sites
  in proteins

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RNA Sequences

• Repository of RNA sequences
• RNA structure data
• RNA metabolism information
• Specialized site by organism, function, etc

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RNA SequencesHyPaLib

• contains annotated structural elements
  characteristic for certain classes of structural
  and/or functional RNAs
• developing software tools that allow a user to
  search sequence databases for any pattern in
  HyPaLib

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RNA SequencesRfam

• a collection of multiple sequence alignments and
  covariance models representing non-coding RNA
  families
• allow the user to search a query sequence against
  a library of covariance models, and view multiple
  sequence alignments and family annotation

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RNA SequencestRNA sequences

• compilation of tRNA Sequences and Sequences of
  tRNA genes

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RNA SequencesOther Examples

• 16S and 23S Ribosomal RNA Mutation Database
• ACTIVITY functional DNA/RNA site activity
• PLANTncRNAs Plant non-coding RNAs
• RNA Modification Database Naturally modified
  nucleosides in RNA

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Structure

• Information on protein structure derived from
  physical data crystallography, NMR
• Classification of proteins according to tertiary
  structures
• Specialized site for specific proteins

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StructureASTRAL

• provides databases and tools useful for analyzing
  protein structures and their sequences
• Partially derived from the SCOP database
  (Structural Classification of Proteins)

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StructureSCOP

• Comprehensive ordering of proteins to know
  structures based on their evolutionary and
  structural relationships
• Protein domains are grouped into species and
  hierarchically classified in families
  superfamilies, folds, and classes

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StructurePDB

• Structure data determined by X-ray
  crystallography and NMR

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Structure Other Examples

• CADB conformation angles of protein structures,
  with associated crystallographic data
• Database of Macromolecular Movements
• DSDBase Disulfide Bonds in proteins
• PSSH alignment between sequences and tertiary
  structures
• SUPERFAMILY Assignments of proteins to
  structural superfamilies

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Other Databases

• Intermolecular Interactions
• Metabolic Pathways and Cellular Regulation
• Pathology
• Proteome Resources
• Retrieval Systems and Database Structure
• Transgenics
• Varied Medical Content

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Other Databases Intermolecular Interactions

• BIND Molecular interactions, complexes and
  pathways
• DIP (Database of Interacting Proteins)
  Experimentally determined protein-protein
  interactions
• KDBI Kinetic data on biomolecular interactions

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Other Databases Metabolic Pathways and Cellular
Regulation

• KEGG Kyoto Encyclopedia of Genes and Genomes
• MetaCyc Metabolic Pathways and Enzymes from
  Various organisms
• PathDB
• EcoCyc E. coli K-12 genome and pathway data
• PRODORIC gene regulation and regulatory
  networks in prokaryotes

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Other DatabasesPathology

• BayGenomics cardiovascular and pulmonary
  disease
• INFEVERS hereditary inflammatory disorder
• GOLD.db lipid-associated disorders
• Mouse Tumor Biology Database

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Other Databases Proteome Resources

• GELBANK 2D gel data repository
• REBASE Restriction enzymes and associated
  methylases
• SWISS-2DPAGE Annotated two-dimensional gel
  electrophoresis database

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Other Databases Retrieval Systems and Database
Structure

• TESS Transcription Element search system
• Virgil Database interconnectivity

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Other DatabasesTransgenics

• Cre Transgenic database Cre transgenic
  mouslines
• Transgenic/targeted mutation database
  information on transgenic animals and targeted
  mutations

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Other Databases Varied Medical Content

• Tree of Life phylogeny and biodiversity
• PubMed biomedical literature
• NCBI Taxonomy Browser organisms with at least
  one sequence deposited in the database
• Pharmgkb Pharmacogenomics and variations in
  drug response based on human variation

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The Rat Genome Database

• Data
• Tools
• Operations

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The Rat Genome Database data

• Genes
• Maps and Markers
• QTLs
• Strains
• Homologs

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The Rat Genome Database tools

• VCMap
• Mapserver
• Meta Gene
• Genome Scanner
• Ontology Browser

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The Rat Genome Database operations

• Curation
• Data QC and Loading
• Data development
• Tool development

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The Rat Genome Database Operations Curation

• Information gathering from peer-reviewed work
• Coordination with other model organism data bases
• Data quality policy development and assessment

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The Rat Genome Database Operations data
development

• Development of data integration strategies
• Development of ontology annotation protocols
• Some development of curation policies
• Outreach
• Ontology development

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The Rat Genome Database Operations tool
development

• Ontology system development
• Systems analysis
• Tool integration
• Tool building
• Software system migration