01-05/12/2014 Computational Metagenomics Workshop University of Mauritius

Fundamentals of Bioinformatics:computation, biology,computational biology

Fundamentals of Bioinformatics:computation, biology,computational biology

Vasilis J. PromponasBioinformatics Research LaboratoryDepartment of Biological Sciences

University of Cyprus

Vasilis J. PromponasBioinformatics Research LaboratoryDepartment of Biological Sciences

University of Cyprus

01-05/12/2014 Computational Metagenomics Workshop University of Mauritius

A short self-introductionA short self-introduction● Vasilis, pronounced: “Vass`ilis”● A Frog Physicist turned into a Biologist

– Coincidence: it all happened around 1995-96

– Computational approach

● PhD in Biology (2004, ComputationalBiology/Bioinformatics), University of Athens,Greece

● 2005 – Moved to Cyprus

01-05/12/2014 Computational Metagenomics Workshop University of Mauritius

Cyprus?Cyprus?Source: http://maps.google.com

01-05/12/2014 Computational Metagenomics Workshop University of Mauritius

Cyprus?Cyprus?

Source: http://maps.google.com

01-05/12/2014 Computational Metagenomics Workshop University of Mauritius

Cyprus?Cyprus?

Source: http://maps.google.com

01-05/12/2014 Computational Metagenomics Workshop University of Mauritius

Cyprus?Cyprus?

01-05/12/2014 Computational Metagenomics Workshop University of Mauritius

University of CyprusUniversity of Cyprus

01-05/12/2014 Computational Metagenomics Workshop University of Mauritius

01-05/12/2014 Computational Metagenomics Workshop University of Mauritius

01-05/12/2014 Computational Metagenomics Workshop University of Mauritius

01-05/12/2014 Computational Metagenomics Workshop University of Mauritius

OverviewOverview● Introduction

– Some definitions and concepts from (Molecular)Biology

– The rapid growth of Biological Data

● The advent of the Genome Era (a paradigmshift in Biology?)

● Bioinformatics and Computational Biology:Fundamental Problems – Concepts –Applications

● Discussion

01-05/12/2014 Computational Metagenomics Workshop University of Mauritius

IntroductionIntroduction

01-05/12/2014 Computational Metagenomics Workshop University of Mauritius

IntroductionBio::revenge

IntroductionBio::revenge

● Biology IS the science of the 21st century

– Used to be a QUALITATIVE scientific domain● Exceptions have been the Rule

– Turning into QUANTITATIVE

– An Information Rich field● Impact in every aspect of (human) lives

– Food production and Quality Control

– Environment (e.g. Ecology, Monitoring,Management)

– Human activities/welfare (e.g. sports, cosmetics,health)

– ...

01-05/12/2014 Computational Metagenomics Workshop University of Mauritius

IntroductionKey actors

IntroductionKey actors

● Genome(s)● Chromosome(s)● Gene(s)● Protein(s)

01-05/12/2014 Computational Metagenomics Workshop University of Mauritius

IntroductionKey actors

IntroductionKey actors

● Genome(s)● Chromosome(s)● Gene(s)● Protein(s)

Source: http://www.google.com

01-05/12/2014 Computational Metagenomics Workshop University of Mauritius

IntroductionKey actors

IntroductionKey actors

● Genome(s)● Chromosome(s)● Gene(s)● Protein(s)

Source: http://www.google.com

But what about some viral genomes?

01-05/12/2014 Computational Metagenomics Workshop University of Mauritius

IntroductionKey actors

IntroductionKey actors

● Genome(s)● Chromosome(s)● Gene(s)● Protein(s)

Source: http://www.google.com

Contains heritable(?) information

01-05/12/2014 Computational Metagenomics Workshop University of Mauritius

IntroductionKey actors

IntroductionKey actors

● Genome(s)● Chromosome(s)● Gene(s)● Protein(s)

✔ Tighly packaged (DNA/RNA/proteins)

✔ 3D-structural organization✔ Contains “functional” regions (a.k.a. genes) and regions of (yet) unknown function

01-05/12/2014 Computational Metagenomics Workshop University of Mauritius

IntroductionKey actors

IntroductionKey actors

● Genome(s)● Chromosome(s)● Gene(s)● Protein(s)

✔ A chromosomal region encoding mRNAs, tRNAs, etc.

✔ Useful keyword: Transcription✔ mRNAs: non-terminal

01-05/12/2014 Computational Metagenomics Workshop University of Mauritius

IntroductionKey actors

IntroductionKey actors

● Genome(s)● Chromosome(s)● Gene(s)● Protein(s)

✔ Main components of the (cellular) toolkit

✔ Linear polymers ✔ Interact with other biological molecules

✔ Useful keyword: Translation

01-05/12/2014 Computational Metagenomics Workshop University of Mauritius

Information Flow in BiologicalSystems

The “Central Dogma”

Information Flow in BiologicalSystems

The “Central Dogma”

PROTEINPROTEIN

RNARNA

DNADNA

Replication

Transcription

Translation

01-05/12/2014 Computational Metagenomics Workshop University of Mauritius

Coupled with a “Universal”genetic code

Coupled with a “Universal”genetic code

The Genetic Code is Degenerate!

01-05/12/2014 Computational Metagenomics Workshop University of Mauritius

… some more complexity ...… some more complexity ...

ORF1 ORF2 ORF3 ORF4

Genome

Chromosomes

DNASequence

Gene (fine)Structure

Amino AcidSequence

E1 E2 E3

01-05/12/2014 Computational Metagenomics Workshop University of Mauritius

...ACTGTCTGACCGGCAGCA...

...TGACAGACTGGCCGTCGT...

DNA stores information ...

01-05/12/2014 Computational Metagenomics Workshop University of Mauritius

Proteins get the dirty job done …

01-05/12/2014 Computational Metagenomics Workshop University of Mauritius

ProteinsProteins● Assembled from one or more polypeptide

chains (homo-/hetero-polymers)● The functional “toolkit”

● Enzymes● Transport-Storage● Motion● Binding● Molecular Recognition● Signal Transduction

● Structural Proteins● Energy Production● Cell Regulation and

Differentiation● ... (...)

01-05/12/2014 Computational Metagenomics Workshop University of Mauritius

F V N Q H L C G S H L V E A L V C G E R G F F Y T P K AY L

G I V E Q C C T S I C S L Y Q L E N Y C Q

SS SS

SS

SS

SS

SS

Chain AChain A

Chain BChain B

Pig Insulin Dimer(PDB_ID:4INS)

MALWTRLLPLLALLALWAPAPAQAFVNQHLCGSHLVEALYLVCGERGFFYTPKARREAENPQAGAVELGGGLGGLQALALEGPPQKRGIVEQCCTSICSLYQLENYCN

Pig Insulin Precursor

Yet, some more complexity(PTMs)

Yet, some more complexity(PTMs)

01-05/12/2014 Computational Metagenomics Workshop University of Mauritius

Back to the “Central doma”Back to the “Central doma”

For (almost) all proteins

FunctionFunction

3D-structure3D-structure

SequenceSequence Determines

Determines • Glucose Uptake PathwayGlucose Uptake Pathway• Glycogen SynthesisGlycogen SynthesisPathwayPathway• Formation ofFormation oftriglyceridestriglycerides

..VEQCCTSICSLYQL..

Again, this “genetic code”is redundant

01-05/12/2014 Computational Metagenomics Workshop University of Mauritius

But, where is the computation inbiology??

But, where is the computation inbiology??

01-05/12/2014 Computational Metagenomics Workshop University of Mauritius

BioinformaticsBioinformatics

Biology

Statistics,Mathematics

Physics,ChemistryEngineeringLinguistics,

...

Informatics,Comput

erScience

Bioinformatics

01-05/12/2014 Computational Metagenomics Workshop University of Mauritius

Bio – related fieldsBio – related fields

● Computational Molecular Biology● Bioinformatics● Theoretical Biology● Biomedical Informatics● ...

● Where are the limits?

01-05/12/2014 Computational Metagenomics Workshop University of Mauritius

A (fuzzy?) definition ofBioinformatics

A (fuzzy?) definition ofBioinformatics

● Bioinformatics is the “computational handling and processing of genetic information”

Ouzounis & Valencia, 2003

01-05/12/2014 Computational Metagenomics Workshop University of Mauritius

Handling Genetic InformationHandling Genetic Information

● Apply existing (or develop custom) efficientmethods for

– Describing and Visualizing

– Storing

– Retrieving

– Integrating

● Large volumes of complex andinhomogeneous data*

*some still call it “Designing and Building Biological Databases”

01-05/12/2014 Computational Metagenomics Workshop University of Mauritius

Handling Genetic Information(part II)

Handling Genetic Information(part II)

● Particular attention:– Origin and Quality of Biological Data

– Data Annotation [Expert-based,(semi-)automatic)

– Interconnectivity

– Friendly to the end-user

01-05/12/2014 Computational Metagenomics Workshop University of Mauritius

Processing Genetic InformationProcessing Genetic Information

● Analysing biological data– AIM I: ADRESSING BIOLOGICAL questions.

● What makes Frodo Baggins (the Hobbit) differfrom Spiderman? (consider that Spiderman'skitsch costume is not a valid answer)

● Does molecule A interact with molecule B?● What is the 3D structure adopted by X?● How does the 3D structure of a molecule

specify its function?– AIM II: ADRESSING other SCIENTIFIC or

TECHNICAL questions

01-05/12/2014 Computational Metagenomics Workshop University of Mauritius

Processing Genetic Information(part II)

Processing Genetic Information(part II)

● Other questions???– Which is the optimal way to store genome data in

a database?

– How can I represent sequences belonging in afamily with a statistical model?

– How can I obtain the optimal pairwiseDNA/RNA/Protein sequence alignment?

– Is their any statistical measure for indicating thesignificance of a sequence comparison score?

01-05/12/2014 Computational Metagenomics Workshop University of Mauritius

A parenthesis (...) for solving acommon misunderstanding

A parenthesis (...) for solving acommon misunderstanding

● Traditional biologists often see Bioinformaticsas a “Black box”

– i.e., predict, then go back in the lab to confirmwith experiment …

● However,

– the computational approach to addressingbiological problems is an experimentalfield on its own

– a single difference: experiments areperformed in silico.

01-05/12/2014 Computational Metagenomics Workshop University of Mauritius

And finally ... what do you meanby “Genetic Information”?

And finally ... what do you meanby “Genetic Information”?

● It can be quite generic– Nucleotide and amino acid sequences

– Three dimensional molecular structuresstructures (proteins, DNA, RNA, sugars,drugs, ...)

– Gene expression data

– Molecular interaction networks

– Complex biological systems (cells, tissues,organisms, ...)

– ... even text in the biomedical literature ...

01-05/12/2014 Computational Metagenomics Workshop University of Mauritius

OMICSOMICS● GenOMICS● TranscriptOMICS● ProteOMICS● MetabolOMICS● KinOMICS● PhylogenOMICS● EpitOMICS

even more ...– BibliOMICS

– DegradOMICS

??? cOMICS ???

Also be aware:

A comprehensive list may be found at the URLhttp://www.genomicglossaries.com/content/omes.asp

01-05/12/2014 Computational Metagenomics Workshop University of Mauritius

Importatnly ...Importatnly ...

●Freely available data

●Accessible software[free/open software]

01-05/12/2014 Computational Metagenomics Workshop University of Mauritius

ر ك شthanksઆ ભ ારmerciशुि क या

ευχαριστώ

ر ك شthanksઆ ભ ારmerciशुि क या

ευχαριστώ