bioinformatics: cool stuff you can do with computers and biology oded magger tel aviv university /...

Bioinformatics:Cool stuff you can do with Computers

and Biology

Oded MaggerTel Aviv University / Autodesk inc.

GIP course 2010

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When two fields come together• Computer science has applications in many

fields (economics, physics, history, you name it.)

• The field of biology is being transformed:• Tons of biological data.

• “Human genome project”• “Large scale experiments”

• Complex computations and algorithms.• Biologists who know how to send an Email.

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Genetics 101

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Genetics 101

DNA

mRNA

Protein

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Challenge examples• Find a drug for a disease.

– Infer its side effects.– Understand how it influences the body.

• Find out what causes genetic disease.• Figure out what a gene actually does.• Decipher the secrets of evolution!!!11

– How similar are two genes?– Construct the tree of life.

• Medical image analysis ( = “sir, I’m afraid you have cancer”).

Case study #1PRINCE:

Associating genes and protein complexes with

hereditary disease

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Background• Objective: to correctly predict the molecular

causing factors of hereditary disease.• Causal genes

• How are causal genes identified today?• Association studies.• Prioritizing genes in an interval.

Done computationally using sequence similarity, functional similarity, network data and more.

• Important insight: proteins causing diseases with similar phenotype tend to lie close in PPI network.

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PPI – “Protein facebook”

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From a problem to an algorithm• Important insight: proteins causing similar

diseases tend to lie close in PPI network.• If many of your friends or friends of friends in

Facebook study computer science, chances are that so are you.

• Similar diseases – Natural Language Processing (the computer reads the diseases encyclopedia).

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From a problem to an algorithm• If related parts of some car break down, the

‘symptoms’ will be similar.

q

d1

d2

d3

d4

d5

0.7

0.9

0.1

0.1

0.3

p2 p3

p4

p10

p5

p7

p6

p8

p9

p1

p11

How does PRINCE work?Interval 10P

p5

p7

p9

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Strengths of PRINCE• A network based method.• Fast, propagation-based method converged to

accurate matrix-based solution.• Global inference:

• Inference not limited to the direct vicinity of genes for which prior knowledge exists.

• Smooth function over the network.• Smart normalizations:

• Logistic transformation of disease similarity metric.

• Edges between two high-degree nodes have lowered weight.

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PRINCE beats the competition!

Case study #2 Metabolic models:

Simulation of life!

(Parts stolen from Tomer Shlomi and Eytan Ruppin)

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Metabolism• The body is a huge factory for

assembling and disassembling molecules ( = stuff).

• Factory workers: special proteins called enzymes.

• A single transformation ofone set of material to another is called “reaction”.A reaction has a rate.(“One worker can turn 2 cows to 50 steaks in one hour.”)

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Metabolic network

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Metabolic simulation!• Start with a set of molecules and their amounts, a

set of enzymes and their amount – and press “play”…

• If you want details – wait until your third year…• Relies on material from the Linear Algebra and

Algorithms courses.

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What is it good for?• Medicine:

• Diagnosis.• Metabolic diseases (any diabetics in the crowd?)• New cures for cancer.

• Biotechnology• Genetically engineered bacteria and yeast

manufacture products of interest with high efficiency (Insulin, bio-fuels, beer).

• Easier to run experiments on a computer than in the lab (1 computer = 1000 lazy biochemists).

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Questions?

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Thank you for listening!