Bioinformatics Databases: Fundamental Concepts of Database Technology

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Bioinformatics DatabasesFundamental Concepts of
Database Technology Data Organization

• Kristen Anton
• Director of BioInformatics
• Dartmouth Medical School

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How can data be organized?

• Paper (i.e. in notebooks)
• Flat files
• Collection of data records
• Minimal structure, no metadata
• Application program must contain relationship
  information
• Database
• Hierarchical
• Network
• Relational

BioInformatics _at_ Dartmouth Medical School
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BioInformatics _at_ Dartmouth Medical School
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How can data be organized?

• Paper (i.e. in notebooks)
• Flat files
• Collection of data records
• Minimal structure, no metadata
• Application program must contain relationship
  information
• Database
• Hierarchical
• Network
• Relational

BioInformatics _at_ Dartmouth Medical School
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What is a relational database?
A database composed of relations and
conforming to a set of principles governing how
such relations are supposed to behave (Codds 12
Rules). There are many database systems that use
tables but dont conform to all of the
principles. These are often called
semirelational systems.
from Understanding SQL,
Martin Gruber

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Practically speaking...

• A database is a body of information stored in two
  dimensions (rows and columns)
• Rows are records
• Columns are attributes of those record entities
  (usually!)
• The groups of rows and columns, or tables, are
  largely independent of each other
• The power of the database lies in the
  relationships that you construct among the tables
• A database is self-describing it contains
  metadata, which is a description of its own
  structure

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What is a Database Management System (DBMS)?

• A set of programs which define, administer and
  process databases and their associated
  applications
• A scalable DBMS can run on multiple platforms
  (varying sizes)
• A DBMS that supports interoperability uses
  industry-standard language and standard ways of
  exchanging data

Examples Oracle, Sybase, 4D, MS Access
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Features of a Relational Database

• Rows (records) are in no particular order
• Columns (fields) are ordered, numbered and named
  names should indicate content of the field
• Primary key uniquely identifies each row -
  ensures that no row is empty, and that every row
  is different from every other row
• Two-step commit process

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Features of a Relational Database

• A view is a subset of the database that an
  application (or user) can process
• The database schema is the structure of the
  entire database
• A constraint is a condition you apply to an
  attribute of a table

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Relationships between tables

• One-to-One, Many-to-One, Many-to-Many
• A join is an operation that combines data from
  multiple tables into a singe result table
• E-R (entity-relationship) diagram is the basic
  graphic to describe the structure of a database

SELECT Sequence.sname, KnownGenes.gname,
KnownGenes.length FROM Sequence,
KnownGenes WHERE KnownGenes.length
Sequence.length
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E-R Diagram
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The tool for communicating withrelational
databases SQL

• Standard Query Language (SQL)
• A query is a question you ask the database, and
  SQL retrieves the appropriate answer set
• Interactive SQL (command line) vs. RAD tool/GUI
• Standardization issue ANSI (American National
  Standards Institute)

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Data Types

• Types of data indicate functions that are
  possible between related fields
• Each field is assigned one data type (imposes
  structure on data)
• Examples text (CHAR, VARCHAR), number (INT,
  DEC) date, time, money binary
• Standardization issue ANSI (American National
  Standards Institute)

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A word about database design

• Designing a database is not trivial
• The value is not in the data, but in the
  structure
• Design to facilitate the retrieval and
  interpretation of the data

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Design database for data extraction think it
through

• Relationships ease extraction and/or reporting of
  data from the system
• Redundancy
• Concept of attributes in rows instead of columns

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Design database for data extraction think it
through
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Design database for data extraction think it
through
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Example BioInformatics Core Technology

• Reusable core modules, with customizable
  components
• Standard business logic framework controls
  transactions (middle layer)
• Metadata-based back-end data storage (facilitates
  data sharing)

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BioInformatics Core Technology
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Data Security High Priority
HIPAA, FIPS 140-2 (VA), IRB requirements
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Life science has become a field which generates
an enormous amount of un-integrated data.
How can methods for data organization help to
solve this problem?
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What is Data Integration?

• Creating a system which allows the extraction of
  a piece or set of information (query result)
  across multiple domains (possibly disparate data
  sources - flat files, databases, spreadsheets,
  URLs...)

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Sample integration problemCancer Biomarker
Discovery

• Clinical center collects blood samples from 1000
  individuals with colon cancer
• Expression analysis reveals that protein x is
  over-expressed in these samples, relative to
  controls
• Could this be a colon cancer biomarker?

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Understanding transcription factors for protein
x production
Show me all genes in the public literature that
are putatively related to protein x, have more
than 4-fold expression differential between
affected and normal tissue and are homologous to
known transcription factors.
Q1 Find homologs
Q2 Find genes with4-fold differential
Q3 Show me genesin public literature
SEQUENCE
EXPRESSION
LITERATURE
(Q1 ? Q2 ? Q3)
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Key components to integration

• Accessing without modifying original data sources
• Handling redundant, conflicting, missing,
  changing (versions) data
• Normalizing analytical data from different data
  sources
• Conforming terminology to industry standards
• Accessing the integrated data as a single
  repository
• Including metadata in repository

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Approaches to Integrationwhere are the key
issues addressed?

• Federated database (poses constraints on original
  data sources fragility in reliance on source
  systems)
• Data warehousing (ETL layer, original data
  sources untouched, required understanding of
  domain, sophisticated update/archive processes)
• Integrating data source profiles
• Indexed Flat Files
• Others.

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Data Warehousing
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Metadataone key to success

• Describes data types, relationships, histories,
  etc.
• Back-end (supports developers), front-end
  (supports users and application)

Data value 55
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Metadataone key to success

• Describes data types, relationships, histories,
  etc.
• Back-end (supports developers), front-end
  (supports users and application)

Data value 55Metadata values Data element
name vehicle speed
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Metadataone key to success

• Describes data types, relationships, histories,
  etc.
• Back-end (supports developers), front-end
  (supports users and application)

Data value 55Metadata values Data element
name vehicle speed Unit miles per hour
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Metadataone key to success

• Describes data types, relationships, histories,
  etc.
• Back-end (supports developers), front-end
  (supports users and application)

Data value 55Metadata values Data element
name vehicle speed Unit miles per
hour Description the average velocity of a
vehicle
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Standardsthe final frontier

• Naming conventions
• Standard coordinate systems
• Unify interpretations of single object types
• Unify software solutions to the same problem
  (also data formats)
• Standards for metadata (incompatible or missing
  metadata)

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Developing Standardsfor Life Sciences Research

• Discovery science does not lend well to
  constraints (especially system constraints)
• Decentralized data management infrastructure,
  competition
• Wildly varying skill levels for data and
  information management

Several groups (Bio-Ontologies, HGNC, OMG, etc.)
and national research initiatives (EDRN, caBIG,
etc.) are taking the lead in the effort to create
workable standards.
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New approach to integrationCancer Biomarker
Discovery

• Network of distributed data silos (does not
  perturb data sources)
• Centralized query and business logic servers,
  accessed through web interface
• CORBA framework manages XML profile definitions
  across the web
• A profile is a set of resource definitions
  implemented in XML for data sources residing in
  one or more distributed systems

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