Global Gene Coexpression Search tool MEM

Preview:

Citation preview

Global Gene Coexpression Search tool MEM

by Anna Ufliand

Bioinformatics Seminar, 30.09.2016

Global Gene Coexpression Search tool MEM

Global Gene Coexpression Search tool MEM

Gene Expression

Central Dogma of Molecular Biology

Image: Your Genome

Central Dogma of Molecular Biology

Image: Your Genome

Central Dogma of Molecular Biology

Image: Your Genome

Central Dogma of Molecular Biology

Image: Your Genome

Central Dogma of Molecular Biology

Image: Your Genome

Central Dogma of Molecular Biology

http://dharmacon.gelifesciences.com/applications/gene-expression/

Gene Expression

http://dharmacon.gelifesciences.com/applications/gene-expression/

Gene Expression

Sample

Biological magic

https://en.wikipedia.org/wiki/DNA_microarray

Measuring Gene Expression

https://en.wikipedia.org/wiki/DNA_microarray

Sample

Biological magic

?

Measuring Gene Expression

https://en.wikipedia.org/wiki/DNA_microarray

Measuring Gene Expression

Sample

Biological magic

https://en.wikipedia.org/wiki/DNA_microarray

Measuring Gene Expression

Sample

Biological magic

https://en.wikipedia.org/wiki/DNA_microarray

Measuring Gene Expression

Sample

Biological magic

https://en.wikipedia.org/wiki/DNA_microarray

Measuring Gene Expression

Sample

Biological magic

https://en.wikipedia.org/wiki/DNA_microarray

Measuring Gene Expression

Experiment

http://advan.physiology.org

Control Test

Sample 1

Sample 2

Sample 3

Sample 4

Sample 5 … Sample

N

Gene 1 45 36 96 23 20 40

Gene 2 10 27 54 50 43 27

Gene 3 13 11 99 61 49 73

Gene 4 61 29 12 0 21 44

Gene 5 8 0 41 72 14 93

Gene 6 0 5 23 7 48 13

… 85

Gene M 12 36 9 81 38 40

DatasetControl TestTestTest Control Control

Sample 1

Sample 2

Sample 3

Sample 4

Sample 5 … Sample

N

Gene 1 0.1967 -1.8514 -0.0115 -0.0809 0.8563 0.8910

Gene 2 -0.7564 1.1564 -0.5080 -0.6347 1.1011 -0.2130

Gene 3 -1.9670 -1.2569 0.4944 1.2508 0.4379 -0.5839

Gene 4 0.4397 -0.4066 -0.5809 -0.2741 -1.5064 2.2165

Gene 5 0.2872 -2.7630 -0.0171 -0.1221 1.2823 1.3415

Gene 6 -1.3435 0.8683 -2.1044 -0.5460 -0.0450 -1.6893

Gene M 0.3125 0.1237 1.6664 -0.9484 0.3885 2.0640

Normalised dataset

Normalised datasetSample

1Sample

2Sample

3Sample

4Sample

5 … Sample N

Gene 1 0.1967 -1.8514 -0.0115 -0.0809 0.8563 0.8910

Gene 2 -0.7564 1.1564 -0.5080 -0.6347 1.1011 -0.2130

Gene 3 -1.9670 -1.2569 0.4944 1.2508 0.4379 -0.5839

Gene 4 0.4397 -0.4066 -0.5809 -0.2741 -1.5064 2.2165

Gene 5 0.2872 -2.7630 -0.0171 -0.1221 1.2823 1.3415

Gene 6 -1.3435 0.8683 -2.1044 -0.5460 -0.0450 -1.6893

Gene M 0.3125 0.1237 1.6664 -0.9484 0.3885 2.0640

Coexpressed genesco

expr

esse

d

Sample 1

Sample 2

Sample 3

Sample 4

Sample 5 … Sample

N

Gene 1 0.1967 -1.8514 -0.0115 -0.0809 0.8563 0.8910

Gene 5 0.2872 -2.7630 -0.0171 -0.1221 1.2823 1.3415

Gene 1

Gene 5

Biological meaning

Gene 1

Gene 5

Biological meaning

Gene 1

Gene 5

Biological meaning

Gene 1

Gene 5

Biological meaning

Sample 1

Sample 2

Sample 3

Sample 4

Sample 5 … Sample

N

Gene 1 0.1967 -1.8514 -0.0115 -0.0809 0.8563 0.8910

Gene 2 -0.7564 1.1564 -0.5080 -0.6347 1.1011 -0.2130

Gene 3 -1.9670 -1.2569 0.4944 1.2508 0.4379 -0.5839

Gene 4 0.4397 -0.4066 -0.5809 -0.2741 -1.5064 2.2165

Gene 5 0.2872 -2.7630 -0.0171 -0.1221 1.2823 1.3415

Gene 6 -1.3435 0.8683 -2.1044 -0.5460 -0.0450 -1.6893

Gene M 0.3125 0.1237 1.6664 -0.9484 0.3885 2.0640

We have a dataset

Sample 1

Sample 2

Sample 3

Sample 4

Sample 5 … Sample

N

Gene 1 0.1967 -1.8514 -0.0115 -0.0809 0.8563 0.8910

Gene 2 -0.7564 1.1564 -0.5080 -0.6347 1.1011 -0.2130

Gene 3 -1.9670 -1.2569 0.4944 1.2508 0.4379 -0.5839

Gene 4 0.4397 -0.4066 -0.5809 -0.2741 -1.5064 2.2165

Gene 5 0.2872 -2.7630 -0.0171 -0.1221 1.2823 1.3415

Gene 6 -1.3435 0.8683 -2.1044 -0.5460 -0.0450 -1.6893

Gene M 0.3125 0.1237 1.6664 -0.9484 0.3885 2.0640

Select query gene

Sample 1

Sample 2

Sample 3

Sample 4

Sample 5 … Sample

N

Gene 1 0.1967 -1.8514 -0.0115 -0.0809 0.8563 0.8910

Gene 5 0.2872 -2.7630 -0.0171 -0.1221 1.2823 1.3415

Gene 6 -1.3435 0.8683 -2.1044 -0.5460 -0.0450 -1.6893

Gene 4 0.4397 -0.4066 -0.5809 -0.2741 -1.5064 2.2165

Gene 3 -1.9670 -1.2569 0.4944 1.2508 0.4379 -0.5839

Gene 2 -0.7564 1.1564 -0.5080 -0.6347 1.1011 -0.2130

Gene M 0.3125 0.1237 1.6664 -0.9484 0.3885 2.0640

Order by coexpression

1 2 3 4 5 … N11 0.4

15.3 0.8

1-2.3 1.9 5.1

2 10.6

27 54 50 42 203 0.1

311 2 87 41 81

4 1.61

52 13 4 18 395 -0.7 0 41 69 14 936 1.1 4 12 6 48 13… 85M1 -0.9 25 98 81 38 40

1 2 3 4 5 … N21 4.1 0.3

69.3 -0.2

32.3 -4.1

2 -2.7 27 54 50 43 273 7.3 11 99 61 49 734 -1.1 29 12 0 21 445 0.7 0 41 72 14 936 -1.1 5 23 7 48 13… 85M2 2.4 36 9 81 38 40

1 2 3 4 5 … N31 4.5 3.6 0.9

6-2.3 2.1

0-4.2

2 -0.1 27 54 50 43 273 1.3 11 99 61 49 734 0.6

129 12 0 21 44

5 -0.8 0 41 72 14 936 0.1 5 23 7 48 13… 85M3 -1.2 36 9 81 38 40

1 2 3 4 5 … N41 0.6 3.6 96 23 20 402 0.1 -2.7 39 50 43 273 -1.1 1.1 99 61 49 734 0.5 4.8 12 0 18 445 -0.8 -2.1

141 72 14 93

6 0.1 1.1 23 7 48 13… 85M4 0.8 0.3 9 81 38 40

1 2 3 4 5 … Nk1 4.5 0.6 0.96 -2.3 20 0.42 -0.1 2.4 543 5.1 43 2.73 1.3 -1.3 1.9 -0.6

149 -7.3

4 -1.1 2.9 0.12 0.12 21 0.445 0.8 0.1 -4.1 0.72 14 0.936 -2.1 -2.7 -0.2

3-0.3 48 1.3

…Mk 1.2 3.6 1.9 8.1 -3.8 -0.4

http://www.ebi.ac.uk/arrayexpress/browse.html

1 2 3 4 5 … N11 0.4

15.3 0.8

1-2.3 1.9 5.1

2 10.6

27 54 50 42 203 0.1

311 2 87 41 81

4 1.61

52 13 4 18 395 -0.7 0 41 69 14 936 1.1 4 12 6 48 13… 85M1 -0.9 25 98 81 38 40

1 2 3 4 5 … N21 4.1 0.3

69.3 -0.2

32.3 -4.1

2 -2.7 27 54 50 43 273 7.3 11 99 61 49 734 -1.1 29 12 0 21 445 0.7 0 41 72 14 936 -1.1 5 23 7 48 13… 85M2 2.4 36 9 81 38 40

1 2 3 4 5 … N31 4.5 3.6 0.9

6-2.3 2.1

0-4.2

2 -0.1 27 54 50 43 273 1.3 11 99 61 49 734 0.6

129 12 0 21 44

5 -0.8 0 41 72 14 936 0.1 5 23 7 48 13… 85M3 -1.2 36 9 81 38 40

1 2 3 4 5 … N41 0.6 3.6 96 23 20 402 0.1 -2.7 39 50 43 273 -1.1 1.1 99 61 49 734 0.5 4.8 12 0 18 445 -0.8 -2.1

141 72 14 93

6 0.1 1.1 23 7 48 13… 85M4 0.8 0.3 9 81 38 40

1 2 3 4 5 … Nk1 4.5 0.6 0.96 -2.3 20 0.42 -0.1 2.4 543 5.1 43 2.73 1.3 -1.3 1.9 -0.6

149 -7.3

4 -1.1 2.9 0.12 0.12 21 0.445 0.8 0.1 -4.1 0.72 14 0.936 -2.1 -2.7 -0.2

3-0.3 48 1.3

…Mk 1.2 3.6 1.9 8.1 -3.8 -0.4

Global coexpression

Measuring global coexpression

Measuring global coexpression

Measuring global coexpression

RRA (Robust Rank Aggregation)

http://genomebiology.biomedcentral.com/articles/10.1186/gb-2009-10-12-r139

gene rank

1 862

2 26

3 1016

4 643

5 504

… …

gene rank

1 320

2 1425

3 370

4 829

5 1250

… …

gene rank

1 976

2 472

3 1013

4 1271

5 1687

… …

gene rank

1 15

2 1026

3 353

4 1356

5 510

… …

Query gene: NANOGds 1 ds 2 ds 3 ds K

RRA

RRA

gene rank

1 862

2 26

3 1016

4 643

5 504

… …

gene rank

1 320

2 1425

3 370

4 829

5 1250

… …

gene rank

1 1076

2 472

3 1013

4 1271

5 1687

… …

gene rank

1 15

2 1026

3 353

4 1356

5 510

… …

Query gene: NANOGds 1 ds 2 ds 3 ds K

RRA

gene rank

1 862

2 26

3 1016

4 643

5 21

… …

gene rank

1 320

2 1425

3 370

4 829

5 9

… …

gene rank

1 1076

2 472

3 1013

4 1271

5 4

… …

gene rank

1 15

2 1026

3 353

4 1356

5 2

… …

Query gene: NANOGds 1 ds 2 ds 3 ds K

RRA

Null hypothesis: uniform distribution of ranks

Significant coexpression: distribution is skewed to lower ranks

1 2 3 4 5 … N11 0.4

15.3 0.8

1-2.3 1.9 5.1

2 10.6

27 54 50 42 203 0.1

311 2 87 41 81

4 1.61

52 13 4 18 395 -0.7 0 41 69 14 936 1.1 4 12 6 48 13… 85M1 -0.9 25 98 81 38 40

1 2 3 4 5 … N21 4.1 0.3

69.3 -0.2

32.3 -4.1

2 -2.7 27 54 50 43 273 7.3 11 99 61 49 734 -1.1 29 12 0 21 445 0.7 0 41 72 14 936 -1.1 5 23 7 48 13… 85M2 2.4 36 9 81 38 40

1 2 3 4 5 … N31 4.5 3.6 0.9

6-2.3 2.1

0-4.2

2 -0.1 27 54 50 43 273 1.3 11 99 61 49 734 0.6

129 12 0 21 44

5 -0.8 0 41 72 14 936 0.1 5 23 7 48 13… 85M3 -1.2 36 9 81 38 40

1 2 3 4 5 … N41 0.6 3.6 96 23 20 402 0.1 -2.7 39 50 43 273 -1.1 1.1 99 61 49 734 0.5 4.8 12 0 18 445 -0.8 -2.1

141 72 14 93

6 0.1 1.1 23 7 48 13… 85M4 0.8 0.3 9 81 38 40

1 2 3 4 5 … Nk1 4.5 0.6 0.96 -2.3 20 0.42 -0.1 2.4 543 5.1 43 2.73 1.3 -1.3 1.9 -0.6

149 -7.3

4 -1.1 2.9 0.12 0.12 21 0.445 0.8 0.1 -4.1 0.72 14 0.936 -2.1 -2.7 -0.2

3-0.3 48 1.3

…Mk 1.2 3.6 1.9 8.1 -3.8 -0.4

Global coexpression

MEM tool (Multi Experiment Matrix)

http://biit.cs.ut.ee/beta_mem/

Quiz

What we learnt today:

• What is gene expression and how to measure it

• What is coexpression and how to measure it

• What is Global coexpression and how to measure it

• What is MEM and how to use it

Quiz

What we learnt today:

• What is gene expression and how to measure it

• What is coexpression and how to measure it

• What is Global coexpression and how to measure it

• What is MEM and how to use it

Quiz

What did we learn today:

• What is gene expression and how to measure it

• What is coexpression and how to measure it

• What is Global coexpression and how to measure it

• What is MEM and how to use it

Quiz

What we learnt today:

• What is gene expression and how to measure it

• What is coexpression and how to measure it

• What is Global coexpression and how to measure it

• What is MEM and how to use it

Quiz

What we learnt today:

• What is gene expression and how to measure it

• What is coexpression and how to measure it

• What is Global coexpression and how to measure it

• What is MEM and how to use it

Recommended