Bioinformatics for Human Biologists

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Bioinformatics for Human Biologists Rasmus Wernersson, Associate Professor Center for Biological Sequence Analysis, DTU [[email protected] - http://www.cbs.dtu.dk/~raz/]

description

Bioinformatics for Human Biologists. Rasmus Wernersson, Associate Professor Center for Biological Sequence Analysis, DTU [ [email protected] - http://www.cbs.dtu.dk/~raz/ ]. Course outline. DTU survival guide. This is a hands-on course. The major part of the course is computer exercises - PowerPoint PPT Presentation

Transcript of Bioinformatics for Human Biologists

Page 1: Bioinformatics for Human Biologists

Bioinformatics for Human Biologists

Rasmus Wernersson, Associate Professor

Center for Biological Sequence Analysis, DTU

[[email protected] - http://www.cbs.dtu.dk/~raz/]

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Course outline

Monday Tuesday Wednesday Thursday Friday

Introduction

Evolution & biological information

DATA

DNA (GenBank)

Protein (UniProt)

Methods

Pairwise alignment

BLAST

DATA

Protein structure

(PDB)

Methods

PyMOL

PSI-Blast

Methods

Multiple alignment

Phylogenetic trees

DATA

Full genome data

Methods

UCSC Genome browser

Prediction methods.

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DTU survival guide

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This is a hands-on course

• The major part of the course is computer exercises

• We get to use the actual methods• We get to use “live” online database

• Reporting:– Short “log book” on each exercise

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Everything is linked from the course programme

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On evolution and sequences

Background information

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Classification: Linnaeus

Carl LinnaeusCarl Linnaeus1707-17781707-1778

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Classification: Linnaeus

• Hierarchical system

– Kingdom– Phylum– Class– Order– Family– Genus– Species

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Classification depicted as a tree

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No “mixed” animals

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Source: www.dr.dk/oline

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Classification depicted as a tree

SpeciesSpecies GenusGenus FamilyFamily OrderOrder ClassClass

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Comparison of limbs

Image source: http://evolution.berkeley.edu

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Theory of evolution

Charles DarwinCharles Darwin1809-18821809-1882

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Phylogenetic basis of systematics

• Linnaeus: Ordering principle is God.

• Darwin: Ordering principle is shared descent from common ancestors.

• Today, systematics is explicitly based on phylogeny.

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Natural Selection: Darwin’s four postulates

• More young are produced each generation than can survive to reproduce.

• Individuals in a population vary in their characteristics.

• Some differences among individuals are based on genetic differences.

• Individuals with favorable characteristics have higher rates of survival and reproduction.

• Evolution by means of natural selection• Presence of ”design-like” features in organisms:• Quite often features are there “for a reason”

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Evolution at the sequence level

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About DNA

• DNA contains the recipes of how to make protein / enzymes.

• Every time a cells divides it’s DNA is duplicated, and each daughter cell gets a copy.

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The DNA alphabet

• The information in the DNA is written in a four letter code: A, T, G, C.

• The DNA can be “sequenced” and the result stored in a computer file.

• ATGGCCCTGTGGAT

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DNA is always written 5’ 3’

5’ AGCC 3’

3’ TCGG 5’

5’ ATGGCCAGGTAA 3’DNA backbone: http://en.wikipedia.org/wiki/DNA(Deoxy)ribose: http://en.wikipedia.org/

Ribose

1

23

4

5

Deoxyribose

1

23

4

5

5’

3’

5’

3’

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• ATGGCCCTGTGGATGCG

Can DNA be changed?

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• ATGGCCCTGTGGATGCG

• ATGGCCCTATGGATGCG

Can DNA be changed?

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A history of mutations

ATGGCCCTGTGTATGCG

ATGGCAATGTGGATGCA

ATGGCCCTGTGGATGCG

ATGGCCCCGTGGATGCG

ATGTCCCCGTGGATGCGATGGCCCCGTGGAACCG

Time

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• Species1: ATGGCAATGTGGATGCA• Species2: ATGGCCCCGTGGAACCG• Species3: ATGTCCCCGTGGATGCG

“DNA alignment”

3

65

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Real life example: Alignment

• Insulin from 7 different species• Homo: ATGGCCCTGTGGATGCGCCTCCTGCCCCTGCTGGCGCTGCTGGCCCTCTGGGGACCTGACCCAGCCGCAGCCTTTGTGAA• Pan: ATGGCCCTGTGGATGCGCCTCCTGCCCCTGCTGGTGCTGCTGGCCCTCTGGGGACCTGACCCAGCCTCGGCCTTTGTGAA• Sus: ATGGCCCTGTGGACGCGCCTCCTGCCCCTGCTGGCCCTGCTGGCCCTCTGGGCGCCCGCCCCGGCCCAGGCCTTCGTGAA• Ovis: ATGGCCCTGTGGACACGCCTGGTGCCCCTGCTGGCCCTGCTGGCACTCTGGGCCCCCGCCCCGGCCCACGCCTTCGTCAA• Canis: ATGGCCCTCTGGATGCGCCTCCTGCCCCTGCTGGCCCTGCTGGCCCTCTGGGCGCCCGCGCCCACCCGAGCCTTCGTTAA• Mus: ATGGCCCTGTTGGTGCACTTCCTACCCCTGCTGGCCCTGCTTGCCCTCTGGGAGCCCAAACCCACCCAGGCTTTTGTCAA• Gallus: ATGGCTCTCTGGATCCGATCACTGCCTCTTCTGGCTCTCCTTGTCTTTTCTGGCCCTGGAACCAGCTATGCAGCTGCCAA

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Real life example: Tree

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Interpretation of Multiple Alignments

Conserved features assumed to be important for functionality

For instance: conserved pairs of cysteines indicate possible disulphide bridge

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• Darwin: all organisms are related through descent with modification

• Prediction: similar molecules have similar functions in different organisms

Protein synthesis carried out by very similar RNA-containing molecular complexes (ribosomes) that are present in all known organisms

Sequences are related

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Sequences are related, II

Related oxygen-binding proteins in humans