S16_Coexpression
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Transcript S16_Coexpression
A Quantitative Overview to Gene Expression Profiling in Animal Genetics
Co-Expression
Validation of alternative methods of data
normalization in gene co-expression studies
Reverter et al. 2005
Bioinformatics 21:1112
Armidale Animal Breeding Summer Course, UNE, Feb. 2006
A Quantitative Overview to Gene Expression Profiling in Animal Genetics
Co-Expression
Motivation
Statistics are like a bikini,
what they reveal is suggestive,
but what they conceal is vital.
Aaron Levenstein
Armidale Animal Breeding Summer Course, UNE, Feb. 2006
A Quantitative Overview to Gene Expression Profiling in Animal Genetics
Co-Expression
Motivation
Correlations Are Dangerous!
Exp 1
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Gene 1
Gene 2
Gene 2
Exp 2
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Gene 1
1 r2
SE (r )
n2
Armidale Animal Breeding Summer Course, UNE, Feb. 2006
A Quantitative Overview to Gene Expression Profiling in Animal Genetics
Co-Expression
Introduction
Validation of alternative methods of data normalization in
gene co-expression studies. Bioinformatics 2005, 21:1112
A. Reverter, W. Barris, S.M. McWilliam, K.A. Byrne,
Y.H. Wang, S.H. Tan, N. Hudson, and B.P. Dalrymple
Experimenta
Hybs.
1. Two breeds by two diets
Cond.
Signalsb
N
Mean
STD
7
4
193,175
7.61
2.99
2. Three diets
14
3
361,320
8.52
2.84
3. Two diets at three ages
24
6
801,807
11.60
1.89
4. Two breeds at three ages
18
6
459,978
8.34
3.28
5. Two fat treatments at two ages
15
4
418,817
7.04
3.31
Expression of each clone (gene) across 23 conditions
Armidale Animal Breeding Summer Course, UNE, Feb. 2006
A Quantitative Overview to Gene Expression Profiling in Animal Genetics
Co-Expression
Introduction
1
4
2
5
3
Armidale Animal Breeding Summer Course, UNE, Feb. 2006
A Quantitative Overview to Gene Expression Profiling in Animal Genetics
Co-Expression
Methods
Expression of each clone (gene) across 23 conditions
Nine Methods of Data Normalization
1. RMNA
Clone i
2. RMCE
3. RMEC
Experiment 2
(E2, E2)
Experiment 1
(E1, E1)
Cond
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2
3
4
5
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x1
(x1 E1 ) / E1
(x 1 Ci ) / Ci
x2
(x 2 E1 ) / E1
(x 2 Ci ) / Ci
x3
(x 3 E1 ) / E1
(x 3 Ci ) / Ci
x4
(x 4 E 2 ) / E 2
(x 4 Ci ) / Ci
x5
(x 5 E 2 ) / E 2
(x 5 Ci ) / Ci
(Ci, Ci)
Armidale Animal Breeding Summer Course, UNE, Feb. 2006
A Quantitative Overview to Gene Expression Profiling in Animal Genetics
Co-Expression
Methods
Expression of each clone (gene) across 23 conditions
Nine Methods of Data Normalization
Armidale Animal Breeding Summer Course, UNE, Feb. 2006
A Quantitative Overview to Gene Expression Profiling in Animal Genetics
Co-Expression
Methods
Expression of each clone (gene) across 23 conditions
Nine Methods of Data Normalization
Armidale Animal Breeding Summer Course, UNE, Feb. 2006
A Quantitative Overview to Gene Expression Profiling in Animal Genetics
Co-Expression
Methods
Expression of each clone (gene) across 23 conditions
Nine Methods of Data Normalization
8.60 9.42 1.93
10.00 9.80 1.55
Armidale Animal Breeding Summer Course, UNE, Feb. 2006
A Quantitative Overview to Gene Expression Profiling in Animal Genetics
Co-Expression
Methods
Expression of each clone (gene) across 23 conditions
Nine Methods of Data Normalization
8.60 9.32 2.17
10.00 9.45 1.95
Armidale Animal Breeding Summer Course, UNE, Feb. 2006
A Quantitative Overview to Gene Expression Profiling in Animal Genetics
Co-Expression
Methods
Expression of each clone (gene) across 23 conditions
Nine Methods of Data Normalization
Expected to be the equal!
Armidale Animal Breeding Summer Course, UNE, Feb. 2006
A Quantitative Overview to Gene Expression Profiling in Animal Genetics
Co-Expression
Methods
Nine Methods of Data Normalization
Log2
Intensities
Mixed-Model Equations
Y ~ MVN X , G g G Aa A Da D VvV e
T
T
Gene x Dye
(RANDOM)
Comparison Group
Array|Block|Dye
(FIXED)
Main Gene
Effect
(RANDOM)
Gene x
Array|Block
(RANDOM)
T
T
Gene x
Variety
(RANDOM)
Residual
(RANDOM)
DE Genes
Armidale Animal Breeding Summer Course, UNE, Feb. 2006
A Quantitative Overview to Gene Expression Profiling in Animal Genetics
Co-Expression
Methods
Nine Methods of Data Normalization
4. MM1NA
5. MM1CE
6. MM1EC
7. MM5NA
8. MM5CE
9. MM5EC
Armidale Animal Breeding Summer Course, UNE, Feb. 2006
A Quantitative Overview to Gene Expression Profiling in Animal Genetics
Co-Expression
Methods
Nine Methods of Data Normalization
4. MM1NA
t̂ c
Vector of BLUP
Clone x Condition
Interaction
7. MM5NA
t̂ E c
5. MM1CE
6. MM1EC
tˆ c c / E
tˆ c E / c
E
8. MM5CE
c
9. MM5EC
tˆ E c c / E
tˆ E c E / c
E
c
Armidale Animal Breeding Summer Course, UNE, Feb. 2006
A Quantitative Overview to Gene Expression Profiling in Animal Genetics
Results
Co-Expression
Observed (RED) vs Expected (BLUE)
Armidale Animal Breeding Summer Course, UNE, Feb. 2006
A Quantitative Overview to Gene Expression Profiling in Animal Genetics
Co-Expression
Results
Average across all pair-wise gene correlations (bold, italics and on
the diagonal); Correlation of correlations (above diagonal); and
maximum absolute discrepancy between methods (below diagonal)
1
2
3
4
5
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7
8
9
1. RMNA
0.53
0.20
0.98
0.11
0.12
0.11
0.06
0.07
0.06
2. RMCE
1.84
0.15
0.21
0.14
0.14
0.14
0.09
0.10
0.09
3. RMEC
0.76
1.79
0.51
0.12
0.12
0.12
0.07
0.07
0.07
4. MM1NA
1.78
1.72
1.74
0.02
0.94
0.99
0.57
0.60
0.56
5. MM1CE
1.75
1.75
1.74
0.51
0.01
0.94
0.61
0.69
0.61
6. MM1EC
1.79
1.71
1.74
0.50
0.55
0.02
0.57
0.61
0.58
7. MM5NA
1.80
1.75
1.79
1.25
1.14
1.21
0.01
0.91
0.99
8. MM5CE
1.78
1.74
1.77
1.19
1.09
1.19
0.59
0.01
0.90
9. MM5EC
1.80
1.75
1.79
1.25
1.13
1.20
0.55
0.66
0.01
Armidale Animal Breeding Summer Course, UNE, Feb. 2006
A Quantitative Overview to Gene Expression Profiling in Animal Genetics
Co-Expression
Results
Redundant genes (ie. those with many
probes on the array) allow for Validation
Armidale Animal Breeding Summer Course, UNE, Feb. 2006
A Quantitative Overview to Gene Expression Profiling in Animal Genetics
Co-Expression
Results
Redundant genes allow for Validation
Armidale Animal Breeding Summer Course, UNE, Feb. 2006
A Quantitative Overview to Gene Expression Profiling in Animal Genetics
Co-Expression
624 Gene Co-Expression
(Alphabetical order)
Results
Robisomal Proteins
Armidale Animal Breeding Summer Course, UNE, Feb. 2006
A Quantitative Overview to Gene Expression Profiling in Animal Genetics
Co-Expression
Brian
Siok Kwee
Applications
Sigrid
Keren
Armidale Animal Breeding Summer Course, UNE, Feb. 2006
A Quantitative Overview to Gene Expression Profiling in Animal Genetics
Co-Expression
Applications
False Discovery Rate as a Function of Correlation
Armidale Animal Breeding Summer Course, UNE, Feb. 2006
A Quantitative Overview to Gene Expression Profiling in Animal Genetics
Co-Expression
Applications
Callipyge Mutation
COL3A1
0.545
UBA52
GNAI2
-0.697
KARS
-0.658
-0.639
TNFRSF21
DLK1
0.584
0.602
LUM
0.611
CIDEC
0. 611
DCAL1
Armidale Animal Breeding Summer Course, UNE, Feb. 2006
A Quantitative Overview to Gene Expression Profiling in Animal Genetics
Co-Expression
Applications
Callipyge Mutation
0.754
-0.822
CAV1
DES
0.747
COL3A1
0.767
CTSF
-0.738
FN1
UBA52
KARS
GNAI2
-0.697
-0.658
SPARC
-0.639
0.743
ACTA1
0.545
0. 799
-0.741
0.853
DLK1
0.584
0.602
LUM
0.611
0. 736
CIDEC
TNFRSF21
TM4SF2
0. 611
DCAL1
0.880
Armidale Animal Breeding Summer Course, UNE, Feb. 2006
A Quantitative Overview to Gene Expression Profiling in Animal Genetics
Co-Expression
Applications
Callipyge Mutation
MYBPC2
0.754
0.883
-0.822
CAV1
LDHA
0.889
DES
0.747
COL3A1
0.767
CTSF
0.853
ACTA1
0.889
MYL1
0.545
0.892
-0.738
FN1
UBA52
0. 799
-0.741
KARS
GNAI2
-0.697
-0.658
SPARC
-0.639
0.743
PGK1
DLK1
0.584
0.602
0.893
LUM
0.611
CASQ1
0. 736
CIDEC
TNFRSF21
TM4SF2
0. 611
DCAL1
0.880
Armidale Animal Breeding Summer Course, UNE, Feb. 2006
A Quantitative Overview to Gene Expression Profiling in Animal Genetics
Co-Expression
Applications
ITM2B
Callipyge Mutation
PYGM
0.916
-0.899
0.972
MYBPC2
0.754
ENO3
0.883
-0.822
CAV1
LDHA
0.897
GPI
0.889
DES
0.747
COL3A1
0.767
CTSF
0.853
ACTA1
0.889
MYL1
0.910
CKM
0.911
0.545
0.892
-0.738
FN1
UBA52
0. 799
-0.741
KARS
GNAI2
-0.697
-0.658
SPARC
-0.639
0.743
PGK1
DLK1
0.584
0.602
0.893
LUM
0.611
CASQ1
0. 736
CIDEC
TNFRSF21
TM4SF2
0. 611
DCAL1
0.880
Armidale Animal Breeding Summer Course, UNE, Feb. 2006