IntroductiontoBioinformatics

IMBB2017RAB,Kigali- RwandaMay02– 13,2017

JoyceNzioki

PlanfortheWeekIntroductiontoBioinformatics

QualityControl

Denovoassembly

BLASTandBiologicaldatabases

DNABarcoding

NucleotidesequenceAnalysis

MSAandPhylogenetics

Sequencedepositing

Resolvingconflicts

Rawsangersequencedata IntroductiontoCLCBio

WhatisBioinformatics

• Bioinformatics is an interdisciplinary sciencethat develops and improves on methods ofstoring, retrieving, organizing and analyzingbiological data.

• This computational techniques are to solvebiological problems and discover the wealth ofbiological information hidden in biologicaldata.

BioinformaticsThedesign,construction anduse ofsoftwaretoolstogenerate,store,annotate andanalyse dataandinformationrelatingtoMolecularBiology.

BioinformaticsThedesign,construction anduse ofsoftwaretoolstogenerate,store,annotate andanalyse dataandinformationrelatingtoMolecularBiology.

Hereweconsidertheuse ofbioinformaticstoolsratherthantheirdesignandconstruction.

Hereweconsidertheaccess,storage andanalysisofdataandinformationitemsratherthanthegenerationandannotation.

Bioinformatics

Experiment Analysis

SequenceStructureFunctionEvolutionPathwayInteractionMutationexpression

Hypothesis

DATA RESULT

Genomes

DNA & RNA sequence

Protein sequence

Protein families, motifs and domains

Protein structure

Protein interactions

Chemical entities

Pathways

Systems

Gene expression

Literature and ontologies

DNA & RNA structure

Major types of Bioinformatics Data

BioinformaticsResearchareasInclude but not limited to

• Organization, classification, dissemination and analysis ofbiological and biomedical data

• Biological sequence analysis and phylogenetics.• Genome organization and evolution• Regulation of gene expression and epiginetics• Biological pathways and network in healthy and disease states• Protein structure prediction from sequence• Modelling and prediction of the biophysical properties ofbiomolecules for binding prediction and drug design

• Design of biomolecular structure and functionWith applications to Biology, Medicine, Agriculture and Industry

Wheredidbioinformaticscomefrom?

Bioinformaticsaroseasmolecularbiologybeguntobetransformedbytheemergenceofmolecularsequenceandstructuraldata

• Recap:Thekeydogmasofmolecularbiology• DNAsequencedeterminedproteinsequence• Proteinsequencedeterminesproteinstructure• Proteinstructuredeterminesproteinfunction• Regulatorymechanisms(e.g.geneexpression)determinestheamountofaparticularfunctioninspaceandtime

Bioinformaticsisnowessentialforthearchiving,organizationandanalysisofdatarelatedtotheseprocesses

Bioinformaticsinvolvestheapplicationofcomputeralgorithms,computermodelsandcomputerdatabaseswiththebroadgoalofunderstandingtheactionofgenes,transcripts,proteinsandlargecollectionsinthisentities

TheintegrationofinformationlearnedaboutthisthreebiologicalprocessesgivesinsightIntothebiologyoforganisms

Howdoesitlooklikeonacomputer

A cDNA sequence (reading frame)

>gi|14456711|ref|NM_000558.3| Homo sapiens hemoglobin, alpha 1 (HBA1), mRNA

ACTCTTCTGGTCCCCACAGACTCAGAGAGAACCCACCATGGTGCTGTCTCCTGCCGACAAGACCAACGTCAAGGCCGCCTGGGGTAAGGTCGGCGCGCACGCTGGCGAGTATGGTGCGGAGGCCCTGGAGAGGATGTTCCTGTCCTTCCCCACCACCAAGACCTACTTCCCGCACTTCGACCTGAGCCACGGCTCTGCCCAGGTTAAGGGCCACGGCAAGAAGGTGGCCGACGCGCTGACCAACGCCGTGGCGCACGTGGACGACATGCCCAACGCGCTGTCCGCCCTGAGCGACCTGCACGCGCACAAGCTTCGGGTGGACCCGGTCAACTTCAAGCTCCTAAGCCACTGCCTGCTGGTGACCCTGGCCGCCCACCTCCCCGCCGAGTTCACCCCTGCGGTGCACGCCTCCCTGGACAAGTTCCTGGCTTCTGTGAGCACCGTGCTGACCTCCAAATACC

GTTAAGCTGGAGCCTCGGTGGCCATGCTTCTTGCCCCTTGGGCCTCCCCCCAGCCCCTCCTCCCCTTCCTGCACCCGTACCCCCGTGGTCTTTGAATAAAGTCTGAGTGGGCGGC

A protein sequence

>gi|4504347|ref|NP_000549.1| alpha 1 globin [Homo sapiens]

MVLSPADKTNVKAAWGKVGAHAGEYGAEALERMFLSFPTTKTYFPHFDLSHGSAQVKGHGKKVADALTNAVAHVDDMPNALSALSDLHAHKLRVDPVNFKLLSHCLLVTLAAHLPAEFTPAVHASLDKFLASVSTVLTSKYR

HowdoweactuallydoBioinformatics?

PrepackagetoolsanddatabasesvManyonlineandopensourcevSomearecommercial

TooldevelopmentvMostlyonUNIXenvironmentvKnowledgeofprogrammingrequires(Python,Perl,R,C,Java)vMayrequirespecializedorhighperformancecomputingresources

HistoryofBioinformatics

HistoryofBioinformatics

Sequencing

DNAsequencingisaprocessofdeterminingtheorderofnucleotideswithinaDNAmolecule.

HistoryofDNAsequencing

• 1976:Maxam – Gilbertsequencing• 1977:Sangersequencing(dideoxy chaintermination)

• 1986:Flourescently labelled ddNTPs• 1987:AppliedBiosystems (ABI370)• 1988:Capillarygell electrophoresis• 1999:AppliedBiosystems ABI3700DNAAnalyzer• 2005>:Nextgenerationsequencing

NextGenerationSequencing

14CTLGH Introduction to Bioinformatics, 13-17 Feb 2017, Nairobi Bert OverduinIntro to NGS Sequencing Technologies

Illumina HiSeqIllumina NextSeqIllumina MiSeqIllumina MiniSeq Illumina NovaSeq

Ion ProtonIon PGM Ion S5

PacBio RS II PacBio Sequel ONT MinION ONT PromethION ONT SmidgION

ApplicationsofBioinformatics• Microbialgenome

applications• Molecularmedicine• Personalizedmedicine• Preventivemedicine• Genetherapy• Drugdevelopment• Antibioticresistance• Evolutionarystudies• Biotechnology• Climatechangestudies• Cropimprovement

• Forensicanalysis• Insectresistance• Improvenutritionalquality• Developmentofdrought

resistantvarieties• Veterinaryscience• Bioengineering• Agriculturebiotechnology.

LimitationsofBioinformatics• Bioinformaticsisascienceofinferencehence:

• Qualityofbioinformaticspredictionsdependsonthequalityofdataandsophisticationofalgorithms.

• Sequencedatamayhaveerrorswhichsubsequentlyleadstoerrorsindownstreamanalysis.

• Manyexhaustivealgorithmscannotbeusedduetocomputationallimitations.

• Trade-offbetweenspecificityandsensitivity

Whybioinformaticsthen•Inmostcasesbiologics/wetlabisneededtovalidatebioinformaticpredictions

•Bioinformaticscan:–Reducedatatoasmallsetoftestablepredictions–Assignadegreeofconfidencetoeachprediction

•Thebiologistwilloftenhavetochoosetheappropriatedegreeofconfidence,dependingon:

–Costofvalidatingpredictions.–Benefitexpectedfromtherightpredictions.

•Datamining- theprocessbywhichtestablehypothesisaregeneratedregardingthefunctionorstructureofageneorproteinofinterestbyidentifyinghomologsinbettercharacterizedorganisms.

•Bioinformaticsasinsillico biology:–Allowsforexplorationofdomainsthatcannotbeaddressedmanuallye.gstudyofpastevolutionaryevents/patterns.

The EndAcknowledgingBertOverduin UniversityorEdinburgh

andEBIonlinecoursesforsomeslides

Thankyou

JoyceNziokij.n.njuguna@cgiar.org

IMBB2017RAB,Kigali- RwandaMay02– 13,2017