global gene coexpression search tool mem
TRANSCRIPT
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