Introduction Introduction toto

Bioinformatics Bioinformatics

Dr. Dr. TaysirTaysir HassanHassan A. A. SolimanSolimanLecturer, Information Systems Dept.Lecturer, Information Systems Dept.

Faculty of Computer and Information Sciences Faculty of Computer and Information Sciences AinAin Shams University Shams University

AgendaAgenda

Definition ofDefinition of BioinformaticsBioinformaticsProgress of the Human Genome ProjectProgress of the Human Genome ProjectThe NCBI Data Model The NCBI Data Model Protein Databases Protein Databases Useful texts Useful texts

Progress of the Human Genome Project From June 2000- April 2003

Bioinformatics Bioinformatics

Roughly,Roughly, BioinformaticsBioinformatics describes use of computers to handle describes use of computers to handle biological information.biological information.In practice:In practice: BioinformaticsBioinformatics = =

““Computational Molecular BiologyComputational Molecular Biology””A tight definition (A tight definition (FredjFredj TekaiaTekaia)): :

"The mathematical, statistical and computing methods that "The mathematical, statistical and computing methods that aim to solve biological problems using DNA and amino aim to solve biological problems using DNA and amino acid sequences and related information.acid sequences and related information.““Distinction between Biomedical &Distinction between Biomedical & Bioinformatics Bioinformatics

Bioinformatics Bioinformatics As technologies improve, we are able to extract more and more As technologies improve, we are able to extract more and more information encoded in a genomeinformation encoded in a genome

biological data

proteins

genes

complexes

pathways

whole cell

community

bio-complexity

organs

Bioinformatics Bioinformatics

1. What is Bioinformatics?

Bioinformatics is the application of computational techniques to

Analyze

Info.

Large Macromolecules

Biological Databases

Organize Understand

Why should I care?Why should I care?

SmartMoneySmartMoney ranksranks BioinformaticsBioinformaticsas #1 among next as #1 among next HotJobsHotJobs

Business Week 50 Masters of Business Week 50 Masters of InnovationInnovation

Jobs available, exciting research Jobs available, exciting research potentialpotential

Important information waiting to Important information waiting to be decoded!be decoded!

http://smartmoney.com/consumer/index.cfm?story=working-june02

Why isWhy is bioinformaticsbioinformatics important?important?

Supply/demand: few people Supply/demand: few people adequately trained in both adequately trained in both biology and computer biology and computer sciencescience

Genome sequencing, Genome sequencing, microarraysmicroarrays, etc lead to large , etc lead to large amounts of data to be amounts of data to be analyzedanalyzed

Leads to important Leads to important discoveries discoveries

Saves time and moneySaves time and money

What skills are needed?What skills are needed?

WellWell--grounded in one of the following areas:grounded in one of the following areas:Computer scienceComputer scienceMolecular biologyMolecular biologyStatisticsStatistics

Working knowledge and appreciation in the Working knowledge and appreciation in the others!others!

In other words,In other words,BioinformaticsBioinformatics integratesintegrates

Biology is a data rich science

From chromosomes to sequence data

Large scale DNA sequencing

CGCCAGCTGGACGGGCACACCATGAGGCTGCTGACCCTCCTGGGCCTTCTGTGTGGCTCGGTGGCCACCCCCTTAGGCCCGAAGTGGCCTGAACCTGTGTTCGGGCGCCTGGCATCCCCCGGCTTTCCAGGGGAGTATGCCAATGACCAGGAGCGGCGCTGGACCCTGACTGCACCCCCCGGCTACCGCCTGCGCCTCTACTTCACCCACTTCGACCTGGAGCTCTCCCACCTCTGCGAGTACGACTTCGTCAAG

Eukaryotic GenomesEukaryotic Genomes

Yeast Yeast : : //genome//genome--www.www.stanfordstanford..eduedu//SaccharomycesSaccharomyces

FlyFly : : //flybase.bio.indiana.edu:7081//flybase.bio.indiana.edu:7081

WormWorm : : //www.//www.sangersanger.ac..ac.ukuk/Projects/C_/Projects/C_eleganselegans

MouseMouse : : //www.//www.ensemblensembl.org/.org/MusMus__musculusmusculus

Puffer FishPuffer Fish : : //www.//www.ensemblensembl.org/.org/FuguFugu__rubripesrubripes

MosquitoMosquito : : //www.//www.ensemblensembl.org/Anopheles_.org/Anopheles_gambiaegambiae

So, what Computer Scientists doSo, what Computer Scientists doforfor BioinformaticsBioinformatics? ?

Computer scientists are responsible for Computer scientists are responsible for INTEGRATING INTEGRATING and and ANALYZINGANALYZING all literature from both patents and all literature from both patents and publications in publications in PubMEDPubMED (MEDLINE) in NCBI(MEDLINE) in NCBI

12 million records

What else?What else?

Computer scientists are responsible for developing tools for Computer scientists are responsible for developing tools for performing various operations, such as BLAST at NCBI performing various operations, such as BLAST at NCBI

Sequence Submission

Area

Statistical Parameters

BLAST Against the Human Genome

Example FASTA sequenceExample FASTA sequence

>JC2395>JC2395

NVSDVNLNKNVSDVNLNK------YIWRTAEKMKYIWRTAEKMK------ICDAKKFARQHKIPESKIDEIEHNSPQDAAEICDAKKFARQHKIPESKIDEIEHNSPQDAAE--------

--------------------------------------------------QKIQLLQCWYQSHGKTQKIQLLQCWYQSHGKT——GACQALIQGLRKANRCDIGACQALIQGLRKANRCDI

AEEIQAMAEEIQAM

>KPEL_DROME>KPEL_DROME

MAIRLLPLPVRAQLCAHLDALMAIRLLPLPVRAQLCAHLDAL----------DVWQQLATAVKLYPDQVEQISSQKQRGRSDVWQQLATAVKLYPDQVEQISSQKQRGRS----------

--------------------------------------------------ASNEFLNIWGGQYNASNEFLNIWGGQYN--------HTVQTLFALFKKLKLHNHTVQTLFALFKKLKLHN

AMRLIKDYAMRLIKDY

>FASA_MOUSE>FASA_MOUSE

NASNLSLSKNASNLSLSK------YIPRIAEDMTYIPRIAEDMT------IQEAKKFARENNIKEGKIDEIMHDSIQDTAEIQEAKKFARENNIKEGKIDEIMHDSIQDTAE--------

--------------------------------------------------QKVQLLLCWYQSHGKSQKVQLLLCWYQSHGKS----DAYQDLIKGLKKAECRRDAYQDLIKGLKKAECRR

TLDKFQDMTLDKFQDM

GenBankGenBank FilesFiles

OneOne--line descriptionsline descriptions

Resources Available through the Resources Available through the OnlineOnline MendelianMendelian Inheritance in Inheritance in

Man (OMIM) Web SiteMan (OMIM) Web Site

Resources Available through the Resources Available through the Cancer Genome Anatomy Project Cancer Genome Anatomy Project

(CGAP) Web Site(CGAP) Web Site

Resources Available through the Resources Available through the Cancer Genome Anatomy Project Cancer Genome Anatomy Project

(CGAP) Web Site(CGAP) Web Site

Some Online Animal Genome Some Online Animal Genome Sources (Part 1)Sources (Part 1)

Some Online Animal Genome Some Online Animal Genome Sources (Part 2)Sources (Part 2)

DrosophilaDrosophila Gene AnnotationGene Annotation

Annotation of Genes on the Annotation of Genes on the SaccharomycesSaccharomyces Genome DatabaseGenome Database

Other Computer Scientists JobsOther Computer Scientists Jobs

Prediction of: Prediction of: EvolutionEvolutionProtein foldingProtein foldingProtein functionProtein function

Computer Computer scienctistsscienctists build mathematical build mathematical models of these processes models of these processes --to infer relationships between components of to infer relationships between components of complex biological systemscomplex biological systems

Protein Databases Protein Databases

BINDINTERACTQuery secondary

databases over the Internet

Computational sequence analysis

Proteins: Prediction of biochemical function

•Relationships between

DNA or amino acidsequence 3D structure protein functions

•Use of this knowledge for prediction of function, molecular modelling, and design (e.g., new therapies)

CGCCAGCTGGACGGGCACACCATGAGGCTGCTGACCCTCCTGGGCCTTCTG…

TDQAAFDTNIVTLTRFVMEQGRKARGTGEMTQLLNSLCTAVKAISTAVRKAGIAHLYGIAGSTNVTGDQVKKLDVLSNDLVINVLKSSFATCVLVTEEDKNAIIVEPEKRGKYVVCFDPLDGSSNIDCLVSIGTIFGIYRKNSTDEPSEKDALQPGRNLVAA

GYALYGSATML

Case Study Case Study Protein DatabasesProtein Databases

Associating Gene Ontology Associating Gene Ontology Molecular Function Molecular Function

Interpro

Signature Databases

PRINTS

Gene Ontology Gene Ontology

AiCR2BRCA1

AssociatedWith OneOr

More

Acid phosohataseAconitate hydratase Basal protein localization

G-Protein coupled receptor

Has one or more

A Gene Product

GO:0003673Is located at

Is involved

in

MolecularFunction

(GO:0003674)

UsedIn

OneOr

More

CellularComponent

(GO:0005575)

BiologicalProcess

(GO:0008150)

Actin filamentMembrane

fraction

INTERPRO

Quick GO PRINTS

BLOCKS: BL00237Database Links

Integral to membrane (GO:0016021)Component

Rhodopsin-like receptor activity (GO:0005164)Function

G-Protein coupled receptor protein signaling pathway (GO:0007186)

Process

IPR000025; Melatonin ReceptorIPR000174; Interleukin-8 Receptor

Children

FamilyType

PF00001: 7tm_1PR00237: GPCRRHODOPSNPS00237: G_Protein_Recep_F1_1PS50262: G_Protein_Recep_F1_2

Signatures

Rhodopsin-like GPCR SuperfamilyName

Matches: 6914 proteinsIPR000276Access. Number

SignaturesOf

ProteinFamilies

Parts of the Children Tree

of GPCRSuperfamily

Gene Ontology Products

5H1A_HUMAN: 5-HYDROXYTRYPTAMINE 1A RECEPTOR (5-HT-1A) (SEROTONIN RECEPTOR) (5- HT1A) (G-21) - HOMO SAPIENS (HUMAN).

5H1A_MOUSE: 5-HYDROXYTRYPTAMINE 1A RECEPTOR (5-HT-1A) (SEROTONIN RECEPTOR) (5- HT1A) - MUS MUSCULUS (MOUSE).

Sequence Titles

5H1A_HUMAN, 5H1A_MOUSE, 5H1A_RAT.True Positives

G protein-coupled receptors (GPCRs) constitute a vast protein family that encompasses a wide range of functions.

Documentation

1. ATTWOOD, T.K. AND FINDLAY, J.B.C. Fingerprinting G protein-coupled receptors.

PROTEIN ENG. 7(2) 195-203 (1994).

Literature References

Interpro: IPR000276, BLOCKS: BL00237, Pfam: PF00001Database References

Rhodopsin-like superfamily signature (GPCR)Title

12-JUL-1992Creation Date

7No. of Motifs

PR00237Accession

GPCRRHODOPSN [View relations][View alignment][View Structure]Identifier

No. of Motifs Included in the Fingerprint

LiteratureReferences

WhereDiscussion

About MotifsAppears

Part of IDs of Protein

Matches for Fingerprints

Part of the Search Result of IPR000276 Fingerprint

- Opsin- Chemokine Receptor- G-Protein, Gamma Subunit

InterproMappings

- Signal Transduction During Conjugation with Cellular Fusion

- Signal Transduction During Conjugation without Cellular Fusion

Child Terms

Gene Ontology (GO:0003673)(P) Biological Process (GO:0008150)

(I) Cellular Process(I) Cell Communication

(I) Signal Transduction

Tree

G-protein coupled receptor protein signaling pathway

Name

GO:0007186Term ID

- Opsin- Histamine H4 Receptor- Peropsin

InterproMappings

- Nucleotide Receptor Activity- Viral Receptor Activity- Amine Receptor Activity

Child Terms

Gene Ontology (GO:0003673)(P) Molecular Function (GO:0008150)

(I) Signal Transducer Activity(I) Receptor Activity (I) Transmembrane Receptor

Activity (I) G-Protein Coupled Receptor

Activity(I) Rhodopsin-like Receptor

Activity

Tree

Rhodopsin-like receptor activityName

GO:0001584Term ID

Part of Quick GO Reference for Biological Process of IPR000276 (GO:0007186)

Part of Quick GO Reference for Molecular Function of IPR000276 (GO:0001584)

-Orexin Receptor-Gastrin Receptor-Galanin Receptor

Interpro Mappings

- Integral to Nuclear Inner Membrane- Integral to Plasma Membrane- Integral to Golgi Membrane

Child Terms

Gene Ontology (GO:0003673)(P) Cellular Component (GO:0005575)

(I) Cell (P) Membrane

(I) Integral to Membrane

Tree

Integral to MembraneName

GO:0016021Term ID

Part of Quick GO Reference for Cellular Component of IPR000276 (GO:0005575)

3. Dump your flat files into a 3. Dump your flat files into a database database

Java Parser

Program

INTERPROXML FLAT

FILES

PRINTSXML FLAT

FILESDBLoader

Quick GOXML FLATFILES

Local Database (BioDB)

Examples of Tables Examples of Tables

Example of Attributes of INTERPRO_GO Table

Part of the Motif Table

Examples of DataExamples of Data

Glycoprotein Hormones Aplha Chain Family, Growth Factor Domain

GLHA_RABIT

Copper Iron Binding Family, Heavy Metal Transport/Detoxification

Protein Domain

COPP_HELFEE

G-Protein Receptor Family3, Extracellular Ligand-Binding

Receptor

MGR4_RAT

G-Protein Receptor Family3, Extracellular Ligand-Binding

Receptor

MGR4_HUMAN

ItemsProtein_id

3’5’Cyclic Nucleotide PhosphodiesteroseDomain, Signal Transduction

CN4D_RAT

3’5’Cyclic Nucleotide PhosphodiesteroseDomain, Signal Transduction

CN4B_HUMAN

Homeobox Protein Antennapedia Type Domain, Nucleus, Regulation of Transcription DNA-Dependent

O42504

Homeobox Protein Antennapedia Type Domain, Nucleus, Regulation of Transcription DNA-Dependent

HXA7_HUMAN

Items Protein name

Examples of Generated Rules Examples of Generated Rules

100%15A protein, which belongs to Family: Mevalonate kinase it most likely contains Domain: GHMP kinases putative ATP-binding domain

R300

100%32A protein, which belongs to Family: G-protein coupled receptors family 3 (Metabotropic glutamate receptor-like) it most likely also contains Domain: Receptor Family ligand binding region

R200

100%32A protein, which belongs to Family: Xeroderma pigmentosum group G/yeast RAD Superfamily it most likely also contains Domain: 5`3`-Exonuclease N- and I- domains

R100

CSDescriptionRid

100%15If a protein is associated with Cellular component: extracellular it most likely contains Domain: Complement C3a, C4a and C5a anaphylatoxin

R600

100%97If a protein is associated with Biological process: potassium transport it most likely contains Domain: Potassium channel

R500

100%24If a protein is associated with Biological Process: defense response it most likely contains Domain: Selectin (CD62E/L/P antigens)

R400

CSDescriptionRid

How about Hardware: How about Hardware: The IBM Blue Gene SupercomputerThe IBM Blue Gene Supercomputer

•Will take on problem of protein folding.

•Protein folding is governed by basic rules of how atoms attract and repel each other, but size of proteins (thousands of atoms) makes it a very difficult problem.

•Will be able to fold a protein of up to 300 amino acids, but this will take a whole year of supercomputing time!

•One quadrillion calculations per second, ~1,000 times faster than Deep Blue that beat world chess champion Garry Kasparov in 1997.

•New architecture of more than one million CPUs. 32 CPUs per chip, bundled with computer memory.

Useful TextbooksUseful Textbooks

Other Useful TextbooksOther Useful Textbooks

Other reference booksOther reference books