A Quantitative Overview to Gene Expression Profiling in Animal Genetics

1
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 211112
Armidale Animal Breeding Summer Course, UNE, Feb.
2006
2
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
3
A Quantitative Overview to Gene Expression
Profiling in Animal Genetics
Co-Expression
Motivation
Correlations Are Dangerous!









Gene 2






















Gene 1
Armidale Animal Breeding Summer Course, UNE, Feb.
2006
4
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, 211112 A. Reverter, W.
Barris, S.M. McWilliam, K.A. Byrne, Y.H. Wang,
S.H. Tan, N. Hudson, and B.P. Dalrymple
Expression of each clone (gene) across 23
conditions
Armidale Animal Breeding Summer Course, UNE, Feb.
2006
5
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
6
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
2. RMCE
3. RMEC
Clone i
Cond

1
Experiment 1 (?E1, ?E1)
2
3
4
Experiment 2 (?E2, ?E2)
5
(?Ci, ?Ci)
Armidale Animal Breeding Summer Course, UNE, Feb.
2006
7
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
8
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
9
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
10
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
11
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
12
A Quantitative Overview to Gene Expression
Profiling in Animal Genetics
Co-Expression
Methods
Nine Methods of Data Normalization
Log2 Intensities
Mixed-Model Equations
Residual (RANDOM)
Gene x Dye (RANDOM)
Gene x Variety (RANDOM)
Comparison Group ArrayBlockDye (FIXED)
Main Gene Effect (RANDOM)
Gene x ArrayBlock (RANDOM)
DE Genes
Armidale Animal Breeding Summer Course, UNE, Feb.
2006
13
A Quantitative Overview to Gene Expression
Profiling in Animal Genetics
Co-Expression
Methods
Nine Methods of Data Normalization
4. MM1NA
5. MM1CE
6. MM1EC
Based on Uni-variate Mixed-Models
7. MM5NA
8. MM5CE
9. MM5EC
Based on Penta-variate Mixed-Models
Armidale Animal Breeding Summer Course, UNE, Feb.
2006
14
A Quantitative Overview to Gene Expression
Profiling in Animal Genetics
Co-Expression
Methods
Nine Methods of Data Normalization
4. MM1NA
5. MM1CE
6. MM1EC
Based on Uni-variate Mixed-Models
Vector of BLUP Clone x Condition Interaction
7. MM5NA
8. MM5CE
9. MM5EC
Based on Penta-variate Mixed-Models
Armidale Animal Breeding Summer Course, UNE, Feb.
2006
15
A Quantitative Overview to Gene Expression
Profiling in Animal Genetics
Co-Expression
Results
Observed (RED) vs Expected (BLUE)
Armidale Animal Breeding Summer Course, UNE, Feb.
2006
16
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)
Armidale Animal Breeding Summer Course, UNE, Feb.
2006
17
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
18
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
19
A Quantitative Overview to Gene Expression
Profiling in Animal Genetics
Co-Expression
Results
624 Gene Co-Expression (Alphabetical order)
Robisomal Proteins
Armidale Animal Breeding Summer Course, UNE, Feb.
2006
20
A Quantitative Overview to Gene Expression
Profiling in Animal Genetics
Co-Expression
Applications
Sigrid
Brian
Keren
Siok Kwee
Armidale Animal Breeding Summer Course, UNE, Feb.
2006
21
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
22
A Quantitative Overview to Gene Expression
Profiling in Animal Genetics
Co-Expression
Applications
Callipyge Mutation
COL3A1
0.545
GNAI2
UBA52
-0.697
0.584
0.602
-0.658
DLK1
LUM
KARS
0.611
-0.639
CIDEC
TNFRSF21
0. 611
DCAL1
Armidale Animal Breeding Summer Course, UNE, Feb.
2006
23
A Quantitative Overview to Gene Expression
Profiling in Animal Genetics
Co-Expression
Applications
Callipyge Mutation
0.754
CAV1
-0.822
DES
0.747
0.853
COL3A1
ACTA1
CTSF
0.545
0.767
GNAI2
UBA52
-0.738
-0.697
FN1
0. 799
0.584
0.602
-0.658
-0.741
DLK1
LUM
KARS
SPARC
0. 736
0.611
-0.639
CIDEC
TNFRSF21
0.743
TM4SF2
0. 611
DCAL1
0.880
Armidale Animal Breeding Summer Course, UNE, Feb.
2006
24
A Quantitative Overview to Gene Expression
Profiling in Animal Genetics
Co-Expression
Applications
Callipyge Mutation
MYBPC2
0.754
0.883
CAV1
LDHA
-0.822
DES
0.889
0.747
0.889
0.853
COL3A1
ACTA1
MYL1
CTSF
0.545
0.767
0.892
GNAI2
UBA52
PGK1
-0.738
-0.697
FN1
0. 799
0.584
0.893
0.602
-0.658
-0.741
DLK1
LUM
KARS
CASQ1
SPARC
0. 736
0.611
-0.639
CIDEC
TNFRSF21
0.743
TM4SF2
0. 611
DCAL1
0.880
Armidale Animal Breeding Summer Course, UNE, Feb.
2006
25
A Quantitative Overview to Gene Expression
Profiling in Animal Genetics
Co-Expression
ITM2B
PYGM
Applications
0.916
-0.899
Callipyge Mutation
0.972
MYBPC2
ENO3
0.754
0.883
0.897
CAV1
LDHA
GPI
-0.822
DES
0.889
0.747
0.889
0.853
0.910
COL3A1
ACTA1
MYL1
CKM
CTSF
0.911
0.545
0.767
0.892
GNAI2
UBA52
PGK1
-0.738
-0.697
FN1
0. 799
0.584
0.893
0.602
-0.658
-0.741
DLK1
LUM
KARS
CASQ1
SPARC
0. 736
0.611
-0.639
CIDEC
TNFRSF21
0.743
TM4SF2
0. 611
DCAL1
0.880
Armidale Animal Breeding Summer Course, UNE, Feb.
2006