Introduction to biological

databases
Wilson Nandolo
[email protected]
+265993375505
Overview
• Genomic research generates
enormous amounts of raw sequence
data.
• The primary challenge with these
data is storage and handling.
Overview
• We will discuss the following aspects of
biological databases
⚫ Type

⚫ Design

⚫ Architecture
Definition of a database
• A database is a computerized archive used
to store and organize data in such a way
that information can be retrieved easily via
a variety of search criteria.
• The chief objective of the development of
a database is to organize data in a set of
structured records to enable easy retrieval
of information.
Definition of a database
• Each record, also called an entry, should contain a
number of fields that hold the actual data items
• For example: fields for
⚫ Names
⚫ Phone numbers
⚫ Addresses
⚫ Dates
Definition of a database
• To retrieve a particular record from the database,
a user can specify a particular piece of
information, called value, to be found in a
particular field and expect the computer to
retrieve the whole data record.
• This process is called making a query.
Databases
• Although data retrieval is the main purpose of all
databases, biological databases often have a higher level
of requirement, known as knowledge discovery
• knowledge discovery refers to the identification of
connections between pieces of information that were
not known when the information was first entered.
• For example, databases containing raw sequence
information can perform extra computational tasks to
identify sequence homology or conserved motifs.
Databases
• These features facilitate the discovery of new biological
insights from raw data.
• Originally, databases all used a flat file format, which is a
long text file that contains many entries separated by a
delimiter, a special character such as a vertical bar (|).
• Within each entry may be many fields separated by tabs
or commas.
Types of databases
• Relational
• Object-oriented
Relational databases
• A set of tables is used to organize data originally in a flat
file
• The tables are related to each other via some unique
attribute
• To execute a query, the system selects linked data items
from different tables and combines the information into
one report.
• Commonly used language: structured query language
(SQL)
Relational databases
Relational databases
• For example, if one is
to ask the question,
which courses are
students from Texas
taking?
• The database will
first find the field for
“State” in Table A
and look up for
Texas.
• This returns students
1 and 5.
Relational databases
• The student numbers are co-listed in Table B, in which
students 1 and 5 correspond to Biol 689 and Math 172,
respectively.
• The course names listed by course numbers are found in
Table C.
Relational databases

• By going to Table C, exact course names corresponding to

the course numbers can be retrieved.
• A final report is then given showing that the Texans are
taking the courses Bioinformatics and Calculus.
Relational databases-advantage
• Executing the same query through the flat file
requires the computer to
⚫ read through the entire text file word by word

⚫ store the information in a temporary memory

space
⚫ mark up the data records containing the word

“Texas”.
• This can easily be done for a small database.
• To perform queries in a large database using flat
files obviously becomes computationally
intensive.
Relational databases-pitfalls
• Another problem with relational
databases is that the tables do not
describe complex hierarchical
relationships between data items
• To overcome this problem, object-oriented
databases have been developed.
Object-oriented databases
• An object can be considered as a unit that
combines data and mathematical routines
that act on the data.
• The database is structured such that the
objects are linked by a set of pointers
defining predetermined relationships
between the objects.
Object-oriented databases
• Searching the database involves navigating
through the objects with the aid of the
pointers linking different objects.
• Programming languages like C++ are used to
create object-oriented databases.
Object-oriented databases
• Using the previous example, three different
objects can be designed
⚫ student object

⚫ course object

⚫ state object.

• Their interrelations are indicated by lines

with arrows.
Object-oriented databases
Object-oriented databases
• To answer the same
question–which
courses are
students from Texas
taking–one simply
needs to start from
Texas in the state
object, which has
pointers that lead
to students 1 and 5
in the student
object.
Object-oriented databases
• Further pointers in
the student object
point to the course
each of the two
students is taking.
• Therefore, a simple
navigation through
the linked objects
provides a final
report.
Object-oriented databases
• The object-oriented database system is
more flexible; data can be structured based
on hierarchical relationships.
• By doing so, programming tasks can be
simplified for data that are known to have
complex relationships, such as multimedia
data.
Object-oriented databases
• However, this type of database system lacks the
rigorous mathematical foundation of the
relational databases.
• There is also a risk that some of the relationships
between objects may be misrepresented.
• Some current databases have therefore
incorporated features of both types of database
programming, creating the object–relational
database management system.
Biological databases
• Based on their contents, biological
databases can be roughly divided into three
categories
⚫ primary databases

⚫ secondary databases, and

⚫ specialized databases
Primary databases
• Contain original biological data.
• Archive raw sequence or structural data
submitted by the scientific community.
Primary databases
• The main primary databases
⚫ GenBank (within NCBI,

https://www.ncbi.nlm.nih.go
v/refseq/)
⚫ DNA Data Bank of Japan (DDBJ,

https://www.ddbj.nig.ac.jp/in
dex-e.html)
⚫ European Molecular Biology

Laboratory database (EMBL,

https://www.ebi.ac.uk/ena/b
rowser/home)
Primary databases
• The three constitute the International
Nucleotide Sequence Database Collaboration.
• Sequence submission to either GenBank,
EMBL, or DDBJ is a precondition for publication
in most scientific journals to ensure the
fundamental molecular data to be made freely
available.
Primary databases
• For the three-dimensional
structures of biological
macromolecules, there is
only one centralized
database, the PDB
(https://www.rcsb.org/).
• This database archives
atomic coordinates of
macromolecules (both
proteins and nucleic acids)
determined by x-ray
crystallography and NMR.
Primary databases
• It uses a flat file format to represent protein
name, authors, experimental details,
secondary structure, cofactors, and atomic
coordinates.
• The web interface of PDB also provides
viewing tools for simple image manipulation.
Secondary databases
• Contain computationally processed or
manually curated information, based on
original information from primary
databases.
• Translated protein sequence databases
⚫ SWISS-Prot
(https://www.expasy.org/resources/unip
rotkb-swiss-prot)
⚫ Protein Information Resources (PIR,
https://proteininformationresource.org/)
Secondary databases
•Some are simple archives of translated
sequence data from identified open
reading frames in DNA.
⚫ TrEMBL (UniProt)
Secondary databases-SWISS-PROT
• This provides detailed sequence annotation that includes
structure, function, and protein family assignment.
• The protein annotation includes
⚫ Function

⚫ domain structure

⚫ catalytic sites

⚫ cofactor binding

⚫ posttranslational modification

⚫ metabolic pathway information

⚫ disease association

⚫ similarity with other sequences.

Secondary databases-SWISS-PROT

• Much of this information is

obtained from scientific
literature and entered by
database curators.
• The data record also
provides cross-referencing
links to other online
resources of interest.
Secondary databases-SWISS-PROT

• Very low redundancy

and high level of
integration with other
primary and
secondary databases
make SWISS-PROT
very popular among
biologists. cs/swiss-
prot_guideline.html
Secondary databases
• A recent effort to combine SWISS-PROT,
TrEMBL, and PIR led to the creation of the
UniProt database, which has larger coverage
than any one of the three databases while at
the same time maintaining the original
SWISS-PROT feature of low redundancy,
cross-references, and a high quality of
annotation.ttps://www.uniprot.org/
• There are also secondary databases that
relate to protein family classification
according to functions or structures.
Specialized databases
• These cater to a particular research interest.
⚫ FlyBase (https://flybase.org/)

⚫ HIV sequence database

(https://www.hsls.pitt.edu/obrc/index.php
?page=URL1101837165)
Specialized databases
• Specialized databases normally serve a
specific research community or focus on
a particular organism.
• The content of these databases may be
sequences or other types of information.
Specialized databases
• The sequences in these databases may overlap with a
primary database but may also have new data
submitted directly by authors.
• Because they are often curated by experts in the
field, they may have unique organizations and
additional annotations associated with the
sequences.
• Many genome databases that are taxonomic specific
fall within this category.
Interconnection between
biological databases
• As mentioned, primary databases are central repositories
and distributors of raw sequence and structure
information.
• They support nearly all other types of biological databases
in a way akin to the MANA providing news feeds to local
news media, which then tailor the news to suit their own
particular needs.
• Therefore, in the biological community, there is a frequent
need for the secondary and specialized databases to
connect to the primary databases and to keep uploading
sequence information.
Interconnection between biological
databases
• In addition, a user often needs to get information from
both primary and secondary databases to complete a task
because the information in a single database is often
insufficient.
• Instead of letting users visiting multiple databases, it is
convenient for entries in a database to be cross-referenced
and linked to related entries in other databases that
contain additional information.
• All these create a demand for linking different databases.
Interconnection between
Biological databases
• The main barrier to linking different biological
databases is format incompatibility
⚫ flat files

⚫ relational

⚫ object oriented.

• The heterogeneous database structures limit

communication between databases.
Interconnection between Biological
databases
• One solution to networking the databases is to use a
specification language called Common Object Request
Broker Architecture (COBRA)
⚫ this allows database programs at different locations to

communicate in a network through an “interface

broker” without having to understand each other’s
database structure.
⚫ It works in a way similar to HyperText Markup Language

(HTML) for web pages, labeling database entries using a

set of common tags.
Interconnection between Biological
databases
• A similar protocol called eXtensible Markup Language
(XML) also helps in bridging databases.
⚫ In this format, each biological record is broken down

into small, basic components that are labeled with a

hierarchical nesting of tags.
⚫ This database structure significantly improves the

distribution and exchange of complex sequence

annotations between databases.
Interconnection between Biological
databases
• Recently, a specialized protocol for bioinformatics data
exchange has been developed.
• It is the distributed annotation system, which allows one
computer to contact multiple servers and retrieve
dispersed sequence annotation information related to a
particular sequence and integrate the results into a single
combined report.
• Example
⚫ The Database for Annotation, Visualization and Integrated

Discovery (DAVID)-https://david.ncifcrf.gov/home.jsp
Pitfalls of biological databases
• One of the problems associated with biological databases is
over-reliance on sequence information and related
annotations, without understanding the reliability of the
information.
• Redundancy is another major problem affecting primary
databases.
⚫ The National Center for Biotechnology Information (NCBI) has
now created a non redundant database, called RefSeq, in
which identical sequences from the same organism and
associated sequence fragments are merged into a single entry.
Pitfalls of biological databases
• The other common problem is erroneous annotations.
• Often, the same gene sequence is found under different names
resulting in multiple entries and confusion about the data.
• Or conversely, unrelated genes bearing the same name are
found in the databases.
• A prominent example of such systems is Gene Ontology.
• Functional annotation databases such as DAVID have the
capacity to deal with these problems.
Pitfalls of biological databases

• Some of the inconsistencies in annotation could be

caused by genuine disagreement between
researchers in the field
⚫ others may result from imprudent assignment of
protein functions by sequence submitters.
 Major biological databases
available on the world-wide web
System Brief Summary of Content URL
AceDB Genome database for www.acedb.org
Caenorhabditis elegans
DDBJ Primary nucleotide sequence www.ddbj.nig.ac.jp
database in Japan
EMBL Primary nucleotide sequence www.ebi.ac.uk/embl/in
database in Europe dex.html

Entrez NCBI portal for a variety www.ncbi.nlm.nih.gov/

of biological databases gquery/gquery.fcgi
ExPASY Proteomics database http://us.expasy.org/
 Major biological databases
available on the world-wide web
System Brief Summary of Content URL
FlyBase A database of the Drosophila http://flybase.bio.indiana.edu/
genome
FSSP Protein secondary structures www.bioinfo.biocenter.helsink
i.fi:8080/dali/index.html
GenBank Primary nucleotide sequence www.ncbi.nlm.nih.gov/Genba
database in NCBI nk

HIV databases HIV sequence data and related www.hiv.lanl.gov/content/inde

immunologic information x

Microarray gene DNA microarray data and www.ebi.ac.uk/microarray

expression database analysis tools
 Major biological databases
available on the world-wide web
System Brief Summary of Content URL
OMIM Genetic information of human diseases www.ncbi.nlm.nih.gov/entrez/q
uery.fcgi?db=OMIM
PIR Annotated protein sequences http://www/pir.georgetown.edu/
pirpirhome3.shtml
PubMed Biomedical literature information www.ncbi.nlm.nih.gov/PubMed
Ribosomal Ribosomal RNA sequences and http://rdp.cme.msu.edu/html
database project phylogenetic trees derived from the
sequences
SRS General sequence retrieval system http://srs6.ebi.ac.uk
SWISS-Prot Curated protein sequence database www.ebi.ac.uk/swissprot/acces
s.html
TAIR Arabidopsis information database www.arabidopsis.org
End of presentation