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Bioinformatics • “half a year in the lab can easily save you an afternoon in front of the computer….” (unknown)

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Page 1: Bioinformatics “half a year in the lab can easily save you an afternoon in front of the computer….” (unknown)

Bioinformatics

• “half a year in the lab can easily save you an afternoon in front of the computer….”

(unknown)

Page 2: Bioinformatics “half a year in the lab can easily save you an afternoon in front of the computer….” (unknown)

Genome analysis - Fall 2002

• Home page: www.birc.dk/studies

• Book: “Bioinformatics: Sequence and Genome Analysis” by D. W. Mount

• Teachers: Leif Schauser, Christian Storm and others

• Instructors: Niels Høgslund Jørgensen

http://www.birc.dk/studies
Page 3: Bioinformatics “half a year in the lab can easily save you an afternoon in front of the computer….” (unknown)
Page 4: Bioinformatics “half a year in the lab can easily save you an afternoon in front of the computer….” (unknown)

Genome projectsOrganism Year Size (Mbp) # of Genes

Saccharomyces cerevisiae

1996 12 5.200

Caenorhabditis elegans

1998 100 19.000

Drosophila melanogaster

2000 115 13.000

Arabidopsis thaliana

2000 115 25.000

Human 2001 2700 39.000

Page 5: Bioinformatics “half a year in the lab can easily save you an afternoon in front of the computer….” (unknown)

Genomes

• First genomes were selected in order to reflect biological diversity.

• Database contains 20 10^9 bp

• Doubling time: 15 month– CPU doubling time 18 month

• Effective tools for sequence analysis needed

Page 6: Bioinformatics “half a year in the lab can easily save you an afternoon in front of the computer….” (unknown)

Bioinformatics Master

Masters Thesis

Algorithms in Bioinformatics

Complex systems Protein structure

Algorithms and Datastructure

Molecular Population Genetics and Evolution

Biostatistics

Basics in Programming

Mathematics basic

Molecular biology basics

Intro: Bioinformatics Genome analysis

Page 7: Bioinformatics “half a year in the lab can easily save you an afternoon in front of the computer….” (unknown)

Discuss with your neighbour

• What do you expect to learn during this course?

Page 8: Bioinformatics “half a year in the lab can easily save you an afternoon in front of the computer….” (unknown)

Topics

• Substitution matrices

• Pairwise alignment

• Multiple alignment

• RNA secondary structure prediction

• Phylogenetic analysis

• Database searching

Page 9: Bioinformatics “half a year in the lab can easily save you an afternoon in front of the computer….” (unknown)

Objectives

• Overview: understanding of topics and techniques– Motivation / principles– Mathematical and statistical models– Algorithms

• User-focus– When and how to use applications

Page 10: Bioinformatics “half a year in the lab can easily save you an afternoon in front of the computer….” (unknown)

Non-objectives

• To learn how to write programs

• To construct mathematical and statistical models

• To improve algorithms

Page 11: Bioinformatics “half a year in the lab can easily save you an afternoon in front of the computer….” (unknown)

Alignment: a central problem

• Alignments are basis of many analysis– Predicting RNA secondary structure– Phylogeny reconstruction– Database searches– Genome analysis mm.

Page 12: Bioinformatics “half a year in the lab can easily save you an afternoon in front of the computer….” (unknown)

Why alignment?

• Discuss with your neighbour:– Which principle does an alignment represent

Page 13: Bioinformatics “half a year in the lab can easily save you an afternoon in front of the computer….” (unknown)

Why alignment?

• Biological sequences are related– Common ancestors– Duplication, mutation, speciation, variation– Principle of evolution

Page 14: Bioinformatics “half a year in the lab can easily save you an afternoon in front of the computer….” (unknown)

Why alignment?

Page 15: Bioinformatics “half a year in the lab can easily save you an afternoon in front of the computer….” (unknown)

What is a Sequence What is a Sequence Alignment? (cont.)Alignment? (cont.)

HIGHLY RELATED:HBA_HUMAN GSAQVKGHGKKVADALTNAVAHVDDMPNALSALSDLHAHKL

G+ +VK+HGKKV A+++++AH+D++ +++++LS+LH KLHBB_HUMAN GNPKVKAHGKKVLGAFSDGLAHLDNLKGTFATLSELHCDKL

RELATED:HBA_HUMAN GSAQVKGHGKKVADALTNAVAHV---D--DMPNALSALSDLHAHKL

++ ++++H+ KV + +A ++ +L L+++H+ KLGB2_LUPLU NNPELQAHAGKVFKLVYEAAIQLQVTGVVVTDATLKNLGSVHVSKG

SPURIOUS ALIGNMENT:HBA_HUMAN GSAQVKGHGKKVADALTNAVAHVDDMPNALSALSD----LHAHKL

GS+ + G + +D L ++ H+ D+ A +AL D ++AH+F11G11.2 GSGYLVGDSLTFVDLL--VAQHTADLLAANAALLDEFPQFKAHQE

How to filter out the last one & pick up the second?

Page 16: Bioinformatics “half a year in the lab can easily save you an afternoon in front of the computer….” (unknown)

Which species are the closest living relatives of modern humans?

Mitochondrial DNA, most nuclear DNA-encoded genes, and DNA/DNA hybridization all show that bonobos and chimpanzees are related more closely to humans than either are to gorillas.

The pre-molecular view was that the great apes (chimpanzees, gorillas and orangutans) formed a clade separate from humans, and that humans diverged from the apes at least 15-30 MYA.

MYA

Chimpanzees

Orangutans Humans

Bonobos

GorillasHumans

Bonobos

Gorillas Orangutans

Chimpanzees

MYA015-30014

Page 17: Bioinformatics “half a year in the lab can easily save you an afternoon in front of the computer….” (unknown)

Ribosome structure

Page 18: Bioinformatics “half a year in the lab can easily save you an afternoon in front of the computer….” (unknown)

Rimosome rRNA

Page 19: Bioinformatics “half a year in the lab can easily save you an afternoon in front of the computer….” (unknown)

Conclusions

• Bioinformatic methods are motivated by the explosion of sequence data

• This course gives a broad introduction to a number of analysis tools

• Most of these tools rely on the principle of evolution

Page 20: Bioinformatics “half a year in the lab can easily save you an afternoon in front of the computer….” (unknown)

Schedule

• Lectures: Tuesdays 9-11, auditorium D1, Department of Mathematical Sciences and on Fridays 9-10, also auditorium D1

• Computer / theoretical exercises take place on Wednesdays 14-17 (HOLD 1), and Thursday 11-14 (HOLD 2) at the Department of Computer Sciences, building 540, room K.16.

Page 21: Bioinformatics “half a year in the lab can easily save you an afternoon in front of the computer….” (unknown)
Page 22: Bioinformatics “half a year in the lab can easily save you an afternoon in front of the computer….” (unknown)

Daimi: some practical things

• Unix introduction

• Computer exercises

• Username / password

• Sign web & user ‘brugererklaeringer’

• Keys / Copy accounts

Page 23: Bioinformatics “half a year in the lab can easily save you an afternoon in front of the computer….” (unknown)

What is a Sequence Alignment?

• HIGHLY RELATED:HBA_HUMAN GSAQVKGHGKKVADALTNAVAHVDDMPNALSALSDLHAHKL

G+ +VK+HGKKV A+++++AH+D++ +++++LS+LH KLHBB_HUMAN GNPKVKAHGKKVLGAFSDGLAHLDNLKGTFATLSELHCDKL

• RELATED:HBA_HUMAN GSAQVKGHGKKVADALTNAVAHV---D--DMPNALSALSDLHAHKL

++ ++++H+ KV + +A ++ +L L+++H+ K

LGB2_LUPLU NNPELQAHAGKVFKLVYEAAIQLQVTGVVVTDATLKNLGSVHVSKG

• SPURIOUS ALIGNMENT:HBA_HUMAN GSAQVKGHGKKVADALTNAVAHVDDMPNALSALSD----LHAHKL

GS+ + G + +D L ++ H+ D+ A +AL D ++AH+F11G11.2 GSGYLVGDSLTFVDLL--VAQHTADLLAANAALLDEFPQFKAHQE

• How to filter out the last one & pick up the second?


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