Global Gene Coexpression Search tool MEM

Global Gene Coexpression Search tool MEM

by Anna Ufliand

Bioinformatics Seminar, 30.09.2016

Gene Expression

Central Dogma of Molecular Biology

Image: Your Genome

Central Dogma of Molecular Biology

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

Gene Expression

Sample

Biological magic

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

Measuring Gene Expression


Sample

Biological magic

?


Sample

Biological magic



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

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

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

… …


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

… …


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 did we learn today:





Quiz

What we learnt today:





Global Gene Coexpression Search tool MEM

Documents

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