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Data Representation
in Bioinformatics
S. Sudarshan
Computer Science and Engg. Dept.
I.I.T. Bombay
Data Representation
 Goal: Represent data in an intuitive and convenient manner
 Without unnecessary replication of information
 Making it easy to write queries to find required information
 Supporting efficient retrieval of required information
 Data Models
 Ad-hoc file formats (not really data models!)
 XML (Extensible Markup Language)
 Relational data model
 Entity-relationship (ER) data model
 Object-relational data model
 Object-oriented data model
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S. Sudarshan, IIT Bombay
Data Representation in Genomics
 Most common approach: Text Files
 E.g. GenBank: GenBank Example
 Advantage:
 Easy to export data to others (integrating datasets is not my problem!)
 Drawback:
 Makes it hard to integrate information from different sources
 This is essential for many applications e.g. comparative studies
 Multiplicity of formats makes interoperation difficult
 Reading a particular file format requires a program designed to “parse”
that file format
 No standard query language
 Complex queries needed to integrate data from different sources
 Several efforts to create standard file formats are based on a “tag”
language called XML
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Genbank Example
LOCUS
DEFINITION
ACCESSION
VERSION
KEYWORDS
SOURCE
ORGANISM
REFERENCE
AUTHORS
TITLE
JOURNAL
FEATURES
source
AB020037 300 bp mRNA EST 11-MAY-1999
AB020037 Phaseolus vulgaris library (Watanabe T)
cDNA, mRNA sequence.
AB020037
AB020037.1 GI:4783241
EST.
Phaseolus vulgaris.
Phaseolus vulgaris
Eukaryota; Viridiplantae; Streptophyta; Embryophyta; …
1 (bases 1 to 300)
Watanabe,T., Watanabe,T, ….
Partial cDNA G.max calnexin homologue from P.vulgaris
Unpublished (1999)
Location/Qualifiers
1..300
/organism="Phaseolus vulgaris"
/db_xref="taxon:3885"
/clone_lib="Phaseolus vulgaris library (Watanabe T)"
92 a 50 c 82 g 76 t
BASE COUNT
ORIGIN
1 gacctgcgat cttctacgaa tcattcgatg aggattttca agatcgttgg atcgtgtctc
61 agaaagagga atacagtggt gtctggaaac atgccaagag tgagggacat gatgatcatg
121 gtcttcttgt cagtgagaaa gcaagaaaat atgccatagt gaaggaactt gacaaggcag
181 tgagtctcag ggatggaact gttgttctcc agtttgaaac tcggcttcag aatggacttg
241 aatgtgaagg agcatatata aaatatctcc gaccacaggg atgctggatg ggaactctaa
//
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S. Sudarshan, IIT Bombay
XML: Extensible Markup Language
 Simple XML example
 E.g. <faculty>
<faculty-member facid=12349>
<name> S.Sudarshan </name>
<email> [email protected]</email>
</faculty-member>
<faculty-member facid=12987>
<name> Pramod Wangikar</name>
<email> [email protected]</email>
</faculty-member>
</faculty>
 Each piece of text enclosed by matching tags <xyz> … </xyz> is
called an element
 Elements may have attributes (such as facid in the example above)
 DTD (Document Type Descriptor) specifies allowed element,
attributes of each element, and what elements may appear within
each element (and how many times and in what order).
 Each application defines a standard set of elements (including how
they are nested) and attributes for each element
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S. Sudarshan, IIT Bombay
XML Representation (Cont.)
 Ad-hoc file representations are being replaced by standard XML
representations (see e.g. http://i3c.open-bio.org)
 Examples:
 Gene Expression Markup Language (GEML) (http://www.geml.org)
– (GEML 2.0 white paper: http://www.geml.org/docs/GEML2_0.pdf)
 Bioinformatic Sequence Markup Language (BSML)
(http://www.labbook.com/products/xmlbsml.asp), and many others
– Earlier GenBank example in in XML (BSML)
 Benefits
 Standardization will simplify inter-operation and data sharing
 XML tagged datasets are easy to read and comprehend
 Parsing of datasets is simple with XML
 Problems:
 Standards take time to develop (for human/political reasons)
 More than one standard may evolve
 People may not adopt standards, sticking to old formats
 Support for querying on XML data is still poor (but will improve)
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S. Sudarshan, IIT Bombay
Genbank Example in XML (BSML)
<?xml version="1.0" ?>
<records>
<record>
<locus name="AB020037" bp="300" strands="" molecule="mRNA"
geometry="linear" division="EST" date="11-MAY-1999"/>
<definition>
<![CDATA[ AB020037 Phaseolus vulgaris library (Watanabe T)
Phaseolus vulgaris cDNA, mRNA sequence ]]>
</definition>
<accession name="AB020037"/>
<version accession="AB020037.1" gi="4783241"/>
<keywords> EST </keywords>
……..
…….
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S. Sudarshan, IIT Bombay
Present vs. Future
 XML databases are coming but not quite here yet
 In alpha versions at best
 Some relational database provide support for storing XML data, but no
support or poor support for quering complex XML data
 XML query language is still being standardized (XQuery)
 Initial XML query implementations likely to be poor compared to
relational query implementations which are mature
 Interesting query execution/optimization problems to be solved, even
ignoring bioinformatics
 Relational data can be viewed as a special case of XML data
 Issues we describe in next few slides also applicable to XML
representation
 XML good for data exchange
 Can easily convert simple XML data to relations
 Perhaps a few years down the road we can use XML for querying
genomics data
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S. Sudarshan, IIT Bombay
What are Relations
Attributes or columns
Name
E-mail
Department
Pramod
Seshadri
Uday
Sudarshan
[email protected]
[email protected]
[email protected]
[email protected]
Chem. Engg.
Mech. Engg.
Elec. Engg.
Comp. Sci.
Tuples or rows
faculty
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S. Sudarshan, IIT Bombay
Relational Representation
 The relational data model is widely used and supported by all the
popular commercial database systems
 Allows
1) information to be broken up into logical units, and then
2) recombined in different ways as required
 Great for queries involving information from multiple original sources
 Can easily gather related information
 e.g. information about a particular gene from multiple
datasets/experiments
 Entity Relationship (E-R) Model:
 Higher level model than the relational model
 Often used for design, and then converted (automatically or
manually) into a relational schema
 Has several diagrammatical representations
 Widely used
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S. Sudarshan, IIT Bombay
Entities and Relationships
 A database can be modeled as:
 a collection of entities,
 relationship among entities.
 An entity is an object that exists and is distinguishable from other
objects.
Example: gene, protein, experiment, organism, person
 Entities have attributes
 An entity set is a set of entities of the same type that share the
same properties.
Example: set of all persons, companies, trees, holidays
 Relationships provide connections between two or more entities
 E.g. Which genes were involved in which experiment
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S. Sudarshan, IIT Bombay
Example ER Diagram for Microarray Data
 Entities represented by boxes, (binary) relationships by lines with names
and optional attributes
 See www.bioinf.man.ac.uk for a more realistic version (the MaxD
database)
Gene
gene-id
sequence
……
Expt-Exptr
Expression-value
value
Expt-Sample
Experiment
Experiment-Id
Date
Image
Notation
*
Many-to-one
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Expt-Array
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Experimenter
Experimenter-Id
Name
E-mail
Dept.
Institution
Sample
Sample-Id
Organism
Cell-type
{Drug-Ids}
Array
Array-Id
Manufacturer
Type
Batch
S. Sudarshan, IIT Bombay
Schema Diagrams for MicroArray Data
 Schema diagrams show multiple relations and their interconnections
 Lines link foreign key with referenced relation
Experimenter
Experimenter-Id
Name
E-mail
Dept.
Institution
Experiment
Experiment-Id
Date
Experimenter-Id
Sample-Id
Array-Id
Image
Expression-Value
Experiment-Id
Gene-Id
value
Sample
Sample-Id
Organism
Cell-type
{Drug-Ids}
Multivalued attribute
Array
Array-Id
Manufacturer
Type
Batch
Gene
Gene-Id
sequence
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S. Sudarshan, IIT Bombay
Modeling Protein Data (from Paton & Goble)
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S. Sudarshan, IIT Bombay
Schema Diagrams vs. ER Notation
 Don’t confuse ER diagrams with schema diagrams
 Differences:
 In ER diagrams:
 lines have names
 There are no explicit foreign key attributes
 In schema diagrams
 Lines don’t have names, but represent foreign key relationships
 Foreign key attributes must be explicitly represented
 Relationships in ER diagrams get converted to separate relations
and/or foreign key relationships (more on this later)
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S. Sudarshan, IIT Bombay
Query Languages
 Language in which user requests information from the database.
 Categories of languages
 Procedural
 E.g. C/C++/Java
 Advantage: Powerful, can specify any query by programming
 Disadvantage: Interfacing directly to database is cumbersome
 non-procedural
 Web forms!
 SQL
 Advantage:
– Can specify query “declaratively” and let database system figure out best
way of finding answers
– Supports queries of medium complexity
 Specialized languages
 More complex queries (e.g. data mining such as classification and clustering)
implemented in procedural language, with SQL acting as interface to
database
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S. Sudarshan, IIT Bombay
Problems of Diversity
 Many different databases
 Multiple databases for each of genome, proteome, transcriptome,
metabolome (and perhaps any other *ome you choose to add!)
 Need to cross-reference between these databases
 Need an ontology to ensure consistent and unique names
 Instability
 Names, data, even models keep changing
 Modeling secondary information
 Annotations, typically text based
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Problems in Querying
 Querying
 What query languages to use? (AceDB (SGD), Icarus (SRS), SQL?)
 OO API (Corba based interfaces proposed by OMG/EMBL)
 Querying and text mining on annotations
 Queries that combine multiple databases and paradigms
 E.g. genome, proteome and annotations (text data)
 Browsing and visualization
 Generate hyperlinks in data automatically for browsing
 Visualization for sequence data, protein structures, to depict
correlations, etc
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S. Sudarshan, IIT Bombay
Problems of Scale and Distribution
 Problems of scale
 Genome: hundreds of gigabytes to terabytes (1012 bytes)
 Transcriptome (Microarray):
 Each chip has 10,000 measurements + image
 Millions of experiments
– on different species/individuals/cells/conditions …
– Total: 1 petabyte/annum (1015 bytes)
 Bottom line: too big to hold everything locally
 Ideally: provide integrated view of all data, and fetch actual data on
demand
 Limited access patterns
 Can usually access data only via predefined Web forms
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S. Sudarshan, IIT Bombay
Problems of Database Representation
 Efficiency and flexibility of use are often at odds
 E.g. the Expression-Value table in our schema can be huge
 Array representation may be better but less convenient for users
 Alternative: use one attribute for each gene
– no database efficiently supports relations with thousands of
attributes
– But this is natural to lay users
 Similarly: user may want one relation for each of millions of
experiments
 Ideal:
 flexible view combined with efficient implementation
underneath, plus
 query languages that offer metadata capabilities
 E.g. “for all relations whose name is in table N”
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S. Sudarshan, IIT Bombay
References
 Online information
 Heaps and heaps of sites, many with actual data
 freely available data may be worth what you paid for it!
 Tutorial on Information Management for Genome Level
Bioinformatics, Paton and Goble, at VLDB 2001:
http://www.dia.uniroma3.it/~vldbproc/#tut
 European Molecular Biology Network http://www.embnet.org/
 Univ. Manchester site (with relational version of Microarray data
representation, and links to other sites)
 http://www.bioinf.man.ac.uk
 Database textbook with absolutely no bioinformatics coverage
(shameless sales pitch ):
 Database System Concepts 4th Ed by Silberschatz, Korth and
Sudarshan (should come out in Indian edition in a few months)
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S. Sudarshan, IIT Bombay
End of Talk
Relational Schema Design Problems
 Many flat file formats have lots of columns:
 E.g.
Drug-effect
Drug1 Drug2 Drug3 … Drug-n
Cancer1
Cancer2
Cancer3
….
Cancer-m
 Beware:
 Such structures are nice for humans to read (are called crosstabs),
BUT
 Most databases cannot support relations with many columns!
 And querying data with such columns is more complicated
 Solution: use a schema
drug-effect(cancer-type, drug, effect)
 Alternative solution: use arrays to represent some such information
(supported by some databases)
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Relational Schema Design Problems (Cont.)
 Another common mistake: having many relations with same
attributes
 E.g. one relation for each cancer type, or one relation for each drug
 Cancer1(…), Cancer2(…), …, Cancer-n(…)
 Most databases can handle only hundreds or a few thousand
relations efficiently
 Querying becomes more complicated when there are many relations
 Solution: Replace many relations with same attributes by a
single relation with the same attributes, plus an extra attribute
storing the name
 Cancer(Type, …)
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S. Sudarshan, IIT Bombay
Alternative E-R Notations
Crow’s feet notation: Total participation (each entity
participates in at least one relationship) is indicated by an
extra bar
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R1
R2
S. Sudarshan, IIT Bombay
E-R Diagram For Our Example
Value
Gene-Id
Expression-Value
Gene
Name
Image
Experiment-Id
E-mail
Experimenter-Id
Date
Dept.
Image
Experiment
Experimenter
Expt-Exptr
Institution
Expt-Sample
Drugs
Expt-Array
Sample-Id
Batch
Array
Sample
Array-Id
Organism
Type
Manufacturer
Cell Type
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S. Sudarshan, IIT Bombay
Relational Schema Design Principles
 Redundancy
 E.g. Array-genes(.., fragment-seq, gene-seq, gene-mutations, …)
 is better represented as
– Array-genes( fragment-seq, gene-id)
– Gene(gene-id, gene-seq, gene-mutations)
 Otherwise data is replicated unnecessarity
– I.e. mutation information is stored multiple times
 Redundancy can be useful for better query performance, but
should be used in a thought-out manner, not by accident
 Inability to express information
 E.g. if a gene is not stored in Array-genes we cannot store its
mutation information
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S. Sudarshan, IIT Bombay
Basic SQL Queries
 Find the image for experiment number 1345
select image
from experiment
where experiment-id = 1345
 Find the experiment-id and image of all experiments involving
e-coli
select experiment-id, image
from experiment, sample
where experiment.sample-id = sample.sample-id and
sample.organism = ‘e-coli’
 All combinations of rows from the relations in the from clause are
considered, and those that satisfy the where conditions are output
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S. Sudarshan, IIT Bombay
Complex Queries and Views
 A view consisting of experiments with number of active genes
create view expt-active-genes as
select experiment-id, count (gene-id) as active-cnt
from experiment, expression-value
where expression-value.experiment-Id =
experiment.experiment-Id
and value > 2
group by branch-name
 Find number of active genes in experiment E-123
select active-cnt
from expt-active-genes
where expirement-Id = ‘E-123’
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S. Sudarshan, IIT Bombay