A Method for Analyzing Time Course Multi-factor Expression Data with Applications to A Burn Study...
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A Method for Analyzing Time Course Multi-factor Expression Data with Applications to A Burn Study Baiyu Zhou Department of Statistics Stanford University 12/08/2008
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Transcript of A Method for Analyzing Time Course Multi-factor Expression Data with Applications to A Burn Study...
A Method for Analyzing Time Course Multi-factor Expression Data with
Applications to A Burn Study
Baiyu ZhouDepartment of
StatisticsStanford University
12/08/2008
Outline
• Motivations
• Brief review: methodology
• Tissue data analysis
• Age impact on survival in adult burn patients
• Data: gene expression at different times after burn injury
• Tissue data (blood, skin, muscle and fat): Questions: 1. what tissue is most affected by burn injury? 2. what tissue contributes most to pediatric and adult differences in burn patients? 3. For a given gene, how is its expression affected in different tissues?
• Age impact on survival in burn patients: Reported dramatically increasing death rate in burn patients over 48 years old (Muller MJ, Pegg SP, Rule MR. Determinants of death following burn injury. Br J Surg. 2001 Apr;88(4):583-7. )
The explanation on gene express level?
Data and Questions
These questions can be addressed by our method !
Brief Review: Methodology (1)
• A novel approach to analyze longitudinal multi-factorial data Example: time course measurements of gene expressions from each patients. longitudinal: time course multi-factorial: factor 1: burn/control ; factor 2: gender (male/ female) • Classify genes into different gene sets. Each gene set represents a different ANOVA structure. Example:
1.0
1.5
2.0
2.5
3.0
C1
gene
exp
ress
ion
burn control
malefemale
1.0
1.5
2.0
2.5
3.0
3.5
4.0
C2
gene
exp
ress
ion
burn control
femalemale
1.0
1.5
2.0
2.5
3.0
C3
gene
exp
ress
ion
burn control
femalemale
0.0
0.5
1.0
1.5
2.0
2.5
3.0
C4
gene
exp
ress
ion
burn control
femalemale
C1: interaction. Gender related burn responsive
C2: additive. Burn and gender effects are independent
C3: only have burn effect, no gender differences
C4: only have gender differences, no burn effect
C5: constant genes
Brief Review: Methodology (2)
• Gene classification is based on information pooling from time course measurements.
• Each gene is associated with an ANOVA direction (in time space), which captures gene specific response features.
• Response timing (when to respond): The magnitude of each component of the ANOVA direction reflects the intensity of ANOVA signal at the corresponding time points.
• Response pattern (how to respond): Negative signs in the ANOVA directions indicate the ANOVA signal is embedded into the expression change between time points. Examples (Burn+Age, time course data)
Application beyond time course data : Tissue Data Analysis
• Tissue data : Gene expressions in blood, skin, muscle and fat were measured for burn patients and controls. • Two factors : burn/control and age (children (<=12 yr)/adults (>=22 yr)).
Questions: Which tissue is mostly affected by burn injury? Which tissue is perturbed most differentially in children and adults? For a gene of interest, how is its expression affected in different tissues?
Analysis • longitudinal multi-factorial data • Treat tissue measurements as a vector• Estimate ANOVA directions in ‘tissue space’
Burn Control
Children 7 9
Adults 11 4
Data :
Tissue Data Analysis (1)
• The total of 11027 probe sets are classified into five gene sets (FDR=0.05).
C1 C2 C3 C4
236 919 5205 21
Examples:
A gene’s ANOVA direction reflects the ANOVA signal intensity in different tissues of that gene
Tissue Data Analysis (2)
• Question: Which tissue contributes most to age related differences in burn patients? • Weight matrix
• First eigen-gene (first right singular vector of W) captures weight distribution among tissues for a gene set.
Muscle
Blo
od
Fat
Skin
2 0 0
1 9 8
2 2 1
5 61 7 1
1 0 6
2 0 3
1 4 8
9 11 8 8
2 3 0
4 6
2 3
1 3 91 8 1
4 2
1 3 2
2 4
6 82 6
1 1 5
1 1 6
1 7 0
2 94 8
9 0
7 5
1 9 6
6 54 0
1 2 9
3 4
5 8
9 2
1 5 19 4
1 0 0
2 3 5
8 7
1 8 22 0 9
6 3
6 4
1 8 3
5 21 5 2
2 0 6
1 6 3
1 8 7
4 57 2
2 2
1 2 6
2 0
1 2 31 5 7
1 2 2
1 1 3
1 2 5
1 4 7
1 81 7 7
2 3 1
1 4 4
1 6 7
6 72 1 4
1 2 0
1 6 2
2 8
1 4 62 0 2
9 8
1 6 6
1
1 78 4
4 4
8 9
1 3 8
6 66 9
4 7
1 6 8
2 2 2
5 71 2 1
1 5 8
7
1 9 3
2 5
1 5 91 1
2 1 5
9 5
1 1 7
1 8 02 2 4
5 9
1 4 3
1 9 2
2 0 74 3
6 0
1 4 1
2 2 6
3 71 1 4
2 0 8
2 3 3
4 1
1 9 08 6
2 2 0
3 0
1 8 6
7 71 7 5
2 0 4
2 7
1 0 1
1 9 1
1 1 22 1 9
1 7 3
6 1
7 3
9 62 2 7
1 3 3
1 9 5
1 9 4
8 39 3
1 5
1 3
7 1
1 3 51 1 8
1 4 5
5 1
2 1 2
1 0 21 4 9
1 0 9
1 6 0
2 2 5
5 0
1 0 43 3
1 3 4
7 6
7 9
2 1 81 1 1
7 4
2 1 0
1 7 9
1 8 52 2 9
1 4
5 3
3 2
1 0 31 0 7
1 8 4
1 5 6
1 6 5
8 05 4
1 2 4
8 8
1 6 9
2 1 31 3 0
1 5 3
8 2
1 2 8
1 6
1 98
3 5
6 2
1 4 0
1 4 22 1
9 9
1 3 7
3 1
1 7 81 1 0
2 3 4
2 1 6
1 6 4
2 2 81 0
1 1 9
1 2 7
1 7 4
4 92 3 2
5 5
1 3 1
9
1 0 81 3 6
3 6
2 2 3
4
1 8 9
63 9
1 9 9
8 5
9 7
1 5 42 3 6
5
1 2
2 1 7
3 81 7 2
7 0
1 5 5
2 1 1
2 0 11 5 0
1 9 7
2 0 5
2
37 8
1 6 1
8 1
1 0 5
1 7 6
Weight Matrix (C1)
-1 0 1Row Z-Score
Color Key
First Eigen Gene (C1)
Blood Skin Muscle Fat
0.2
0.3
0.4
0.5
0.6
0.7
Tissue Data Analysis (3)
• Age differences are strong in muscle, fat and skin after burn injury (C1 and C2 genes) • Gene expressions in blood are perturbed most by burn injury (C3)
First Eigen Gene (C1)
Blood Skin Muscle Fat
0.2
0.3
0.4
0.5
0.6
0.7
First Eigen Gene (C2)
Blood Skin Muscle Fat
0.35
0.40
0.45
0.50
0.55
First Eigen Gene (C3)
Blood Skin Muscle Fat
0.35
0.45
0.55
0.65
First Eigen Gene (C4)
Blood Skin Muscle Fat
0.3
0.4
0.5
0.6
0.7
Mus
cle
Blo
od Fat
Ski
n
2 0 0
1 9 8
2 2 1
5 61 7 1
1 0 6
2 0 3
1 4 8
9 11 8 8
2 3 0
4 6
2 3
1 3 91 8 1
4 2
1 3 2
2 4
6 82 6
1 1 5
1 1 6
1 7 0
2 94 8
9 0
7 5
1 9 6
6 54 0
1 2 9
3 4
5 8
9 2
1 5 19 4
1 0 0
2 3 5
8 7
1 8 22 0 9
6 3
6 4
1 8 3
5 21 5 2
2 0 6
1 6 3
1 8 7
4 57 2
2 2
1 2 6
2 0
1 2 31 5 7
1 2 2
1 1 3
1 2 5
1 4 7
1 81 7 7
2 3 1
1 4 4
1 6 7
6 72 1 4
1 2 0
1 6 2
2 8
1 4 62 0 2
9 8
1 6 6
1
1 78 4
4 4
8 9
1 3 8
6 66 9
4 7
1 6 8
2 2 2
5 71 2 1
1 5 8
7
1 9 3
2 5
1 5 91 1
2 1 5
9 5
1 1 7
1 8 02 2 4
5 9
1 4 3
1 9 2
2 0 74 3
6 0
1 4 1
2 2 6
3 71 1 4
2 0 8
2 3 3
4 1
1 9 08 6
2 2 0
3 0
1 8 6
7 71 7 5
2 0 4
2 7
1 0 1
1 9 1
1 1 22 1 9
1 7 3
6 1
7 3
9 62 2 7
1 3 3
1 9 5
1 9 4
8 39 3
1 5
1 3
7 1
1 3 51 1 8
1 4 5
5 1
2 1 2
1 0 21 4 9
1 0 9
1 6 0
2 2 5
5 0
1 0 43 3
1 3 4
7 6
7 9
2 1 81 1 1
7 4
2 1 0
1 7 9
1 8 52 2 9
1 4
5 3
3 2
1 0 31 0 7
1 8 4
1 5 6
1 6 5
8 05 4
1 2 4
8 8
1 6 9
2 1 31 3 0
1 5 3
8 2
1 2 8
1 6
1 98
3 5
6 2
1 4 0
1 4 22 1
9 9
1 3 7
3 1
1 7 81 1 0
2 3 4
2 1 6
1 6 4
2 2 81 0
1 1 9
1 2 7
1 7 4
4 92 3 2
5 5
1 3 1
9
1 0 81 3 6
3 6
2 2 3
4
1 8 9
63 9
1 9 9
8 5
9 7
1 5 42 3 6
5
1 2
2 1 7
3 81 7 2
7 0
1 5 5
2 1 1
2 0 11 5 0
1 9 7
2 0 5
2
37 8
1 6 1
8 1
1 0 5
1 7 6
Weight Matrix (C1)
-1 0 1Row Z-Score
Color Key
Bloo
d
Fat
Mus
cle
Skin
2 5 55 08 06 2 52 6 42 8 66 48 0 93 1 43 5 27 7 89 0 56 7 44 1 04 4 64 2 74 95 1 86 1 55 1 25 1 38 8 44 1 14 6 35 5 17 9 36 4 98 3 31 6 52 4 05 8 29 1 56 2 79 0 08 6 71 2 28 7 73 2 08 4 86 3 14 6 88 8 11 3 87 53 5 33 2 34 0 56 7 18 9 73 6 34 5 98 0 14 42 6 33 7 15 4 22 9 16 9 12 85 3 96 7 62 6 82 0 67 1 11 4 02 2 66 5 92 1 73 1 83 2 55 8 82 3 98 9 91 1 25 6 84 8 37 0 76 78 5 92 8 24 1 69 0 77 9 78 9 85 4 64 2 55 5 85 8 18 6 17 7 23 7 49 0 29 97 2 96 8 26 8 16 0 21 1 03 2 74 9 17 6 21 44 86 0 34 9 27 93 8 22 3 75 7 04 8 58 5 28 36 6 73 2 15 4 33 8 91 3 11 3 31 1 75 9 15 8 94 26 32 49 81 6 06 1 92 3 32 7 91 6 37 3 31 5 58 1 13 91 9 44 6 01 0 85 5 62 1 32 9 83 6 53 6 73 9 25 7 33 3 86 7 95 6 43 9 72 5 36 9 63 4 86 2 25 3 18 1 44 5 85 2 87 0 21 0 03 1 62 7 14 5 01 35 5 57 7 76 3 58 9 41 8 14 4 01 1 48 2 88 8 56 1 72 7 66 3 05 1 77 3 97 1 68 4 49 1 64 1 94 61 97 6 01 5 03 6 05 8 32 0 32 7 37 47 0 59 73 5 65 9 05 85 1 18 5 61 11 5 75 4 98 1 63 7 57 4 35 7 27 3 26 4 55 3 69 1 88 2 08 18 2 35 0 23 7 87 4 81 66 0 68 5 11 1 38 0 86 6 98 7 07 6 88 99 0 87 2 77 25 3 21 4 94 3 58 0 37 68 2 41 3 63 3 986 1 234 3 98 73 9 33 21 9 51 3 73 1 25 4 75 9 22 4 36 7 88 9 05 0 06 7 22 4 22 5 23 3 68 4 26 1 12 5 948 6 22 0 06 0 78 3 11 1 58 0 23 521 8 83 4 47 0 66 9 23 9 96 94 1 54 7 16 3 76 7 57 0 17 6 63 2 98 2 92 0 76 2 09 1 24 0 14 9 03 0 03 7 22 7 88 3 87 5 57 0 47 3 83 82 5 67 3 05 6 93 5 77 8 87 3 77 9 42 15 9 56 5 83 6 97 1 43 8 38 6 81 5 18 1 98 7 83 3 13 5 95 7 86 3 25 7 73 9 87 8 41 3 48 6 54 3 45 3 81 2 88 9 14 6 46 9 91 0 33 7 07 4 08 5 54 3 84 6 24 9 31 6 15 3 31 1 15 4 01 84 15 7 11 6 27 6 55 2 06 4 79 1 12 2 48 7 94 9 48 88 4 34 5 64 6 95 0 43 9 02 1 92 4 72 6 18 4 14 4 95 2 55 0 32 4 17 4 67 5 82 9 26 3 38 8 01 9 62 9 34 7 54 7 44 4 78 6 49 67 1 77 0 37 5 48 51 5 24 01 0 56 2 68 1 54 0 65 9 96 5 63 6 27 5 04 4 55 0 52 2 58 4 74 8 46 4 64 3 03 0 85 26 0 02 6 96 5 09 38 2 61 0 92 0 15 8 07 4 78 6 03 2 26 5 54 0 77 3 43 72 5 73 2 866 3 66 1 08 9 66 1 67 8 22 2 07 9 22 6 78 8 96 17 2 83 6 16 8 48 2 78 3 02 57 1 57 4 46 3 82 1 04 0 83 8 44 5 55 5 27 9 06 03 0 27 5 91 8 38 4 51 6 91 6 66 4 45 9 82 3 17 8 51 3 25 1 92 5 48 0 53 3 59 26 8 51 76 7 05 64 8 67 2 315 5 33 0 36 5 33 5 55 4 46 2 15 6 35 8 53 0 48 7 31 3 91 9 93 4 92 5 81 5 98 6 64 38 1 71 6 74 8 08 1 86 9 07 33 4 15 1 55 6 65 9 34 4 47 1 05 5 96 1 46 5 46 9 37 14 5 26 0 57 6 92 7 22 7 57 7 91 5 49 17 8 33 4 65 5 47 8 77 1 27 1 32 3 22 6 26 6 41 0 76 6 64 2 65 8 62 6 57 6 14 9 55 16 0 85 52 3 02 22 8 55 9 75 71 9 71 5 88 3 71 3 54 9 91 4 64 3 27 83 2 61 2 41 8 75 2 16 5 15 0 78 3 47 2 07 6 31 08 4 03 4 08 5 34 6 19 51 8 65 4 12 0 86 6 02 9 05 92 0 27 0 92 75 1 01 7 02 9 51 7 83 0 63 3 48 7 26 21 4 52 9 97 0 88 8 76 2 84 7 38 1 21 7 36 6 81 0 63 9 51 7 53 0 53 18 9 34 9 83 8 85 0 83 4 74 1 25 2 66 1 81 4 71 0 14 4 84 4 28 4 94 0 49 1 71 6 83 5 12 6 61 7 72 8 46 9 58 0 64 2 04 2 44 8 26 87 5 11 9 04 9 71 5572 5 07 8 95 0 95 4 53 8 66 2 92 2 78 6 31 2 54 7 07 5 32 2 97 7 03 0 75 2 72 9 76 8 84 4 36 9 41 8 44 5 72 8 13 1 71 3 02 1 43 9 66 7 37 5 64 1 88 0 45 3 45 3 77 2 68 8 21 7 95 6 01 6 43 1 14 2 32 4 93 3 75 2 97 2 57 3 54 0 32 9 66 4 82 7 08 3 62 9 43 1 91 4 84 3 61 1 63 6 44 3 31 2 09 0 36 4 37 7 36 8 67 9 52 4 58 7 17 7 48 4 61 7 18 5 84 3 78 7 61 28 0 02 8 86 4 23 62 2 13 5 05 0 18 8 69 0 13 0 98 6 96 8 77 4 53 6 69 1 48 5 04 6 56 3 44 1 36 9 74 2 12 1 64 2 86 0 15 7 63 5 44 0 07 0 08 7 51 4 39 1 93 2 41 7 22 66 0 43 34 76 2 36 3 92 2 34 5 15 9 67 8 18 1 06 0 92 8 34 56 5 75 0 691 4 26 6 28 9 58 8 89 1 04 0 26 6 33 8 17 5 29 0 48 3 28 9 23 1 06 4 02 2 23 9 45 3 02 1 53 8 03 5 87 2 24 8 76 5 22 4 63 0 18 5 46 1 31 5 66 8 91 2 65 4 81 8 25 5 71 4 42 3 85 6 75 39 07 8 68 42 4 87 9 64 3 15 2 42 0 94 5 43 3 01 1 88 62 6 02 1 84 0 97 9 87 05 1 42 1 29 0 96 9 82 02 8 97 3 64 2 25 3 54 1 75 7 49 1 33 8 77 7 18 1 31 9 85 6 16 8 38 3 97 1 81 2 91 9 38 7 41 4 17 1 98 8 32 8 71 2 73 41 0 44 1 41 0 25 8 47 2 49 0 67 6 78 2 52 7 43 1 58 2 15 6 55 7 91 5 33 05 7 51 8 02 32 3 51 9 22 1 12 8 04 7 73 4 34 5 32 97 9 94 6 61 9 13 6 86 8 06 57 7 55 5 08 5 71 7 62 5 13 7 34 8 93 7 75 2 38 3 57 3 13 9 16 4 12 7 78 0 78 2 22 3 63 4 56 2 43 7 97 7 67 72 0 43 3 35 8 77 6 42 3 41 2 11 8 96 6 12 0 55 2 24 8 17 4 22 4 43 1 35 6 24 7 85 1 64 4 11 2 31 8 52 2 87 4 14 9 66 7 76 63 4 28 27 5 75 9 44 6 77 4 99 44 2 91 1 97 8 07 9 17 2 11 7 45 44 7 24 8 83 3 24 7 93 8 56 6 53 7 64 7 6
Weight Matrix (C2)
-1 0 1Row Z-Score
Color Key
Ski
n
Mus
cle Fat
Blo
od
7 7 07 9 16 3 29 4 14 3 08 0 05 2 73 0 74 2 07 1 59 0 72 9 18 0 44 9 98 2 08 1 88 9 06 6 77 1 37 7 19 7 08 5 27 8 29 0 66 4 88 8 65 8 47 1 08 3 97 9 89 5 75 8 35 5 19 5 25 8 08 0 74 8 14 9 07 8 39 2 94 2 39 0 98 5 69 6 99 2 79 4 81 3 63 7 58 8 36 7 56 3 47 4 05 9 17 9 61 8 59 3 19 8 47 77 4 86 3 63 0 17 9 06 7 98 4 78 7 63 8 46 6 37 7 49 8 73 1 37 5 83 0 58 1 24 7 95 2 89 1 29 4 47 2 59 4 92 7 55 3 49 8 29 9 19 0 29 4 58 7 14 4 35 2 99 9 69 9 07 4 48 5 17 5 18 3 36 3 36 8 09 8 07 5 28 9 27 3 55 3 67 2 16 9 88 6 46 5 15 5 34 5 39 1 15 5 78 2 45 8 66 6 06 0 08 7 88 9 86 3 77 4 13 8 15 4 72 5 56 9 79 5 42 2 06 2 76 6 89 6 55 8 16 4 43 5 55 2 07 0 87 8 48 1 08 9 95 4 58 5 58 6 69 5 07 2 99 8 58 5 99 1 57 8 78 5 07 0 22 8 55 5 05 1 97 0 97 3 95 0 27 0 07 5 08 4 97 3 08 9 36 8 27 3 16 6 26 4 27 6 48 3 65 1 08 0 94 5 59 0 45 7 54 2 69 6 67 1 16 7 19 9 72 1 81 42 95 9 63 5 78 5 32 8 46 8 87 5 71 6 57 0 187 1 85 79 13 9 66 4 62 5 64 91 2 73 4 49 3 08 55 1 451 1 33 52 2 95 9 48 8 25 54 2 21 4 81 4 34 9 71 0 21 7 21 68 8 83 5 32 49 6 11 5 21 9 78 1 59 9 99 72 5 99 8 14 31 3 714 85 827 24 1 31 2 15 31 22 6 03 6 491 18 42 2 43 7 93 2 82 1 12 031 6 23 9 45 03 0 03 2 11 5 93 9 52 9 04 7 23 72 1 33 6 69 2 01 34 8 93 44 13 2 72 9 45 6 38 12 6 54 5 83 7 34 8 53 0 34 0 03 3 74 1 54 08 0 54 1 27 2 67 4 38 3 78 6 12 12 8 65 5 58 1 38 68 2 15 3 89 6 88 9 46 3 11 0 0 02 3 85 5 87 9 46 5 51 8 12 4 62 6 164 4 54 28 0 11 0 59 0 31 0 76 5 91 1 68 1 76 2 01 7 12 6 71 9 32 7 75 12 5 76 32 9 23 2 31 2 674 71 2 21 3 16 2 15 8 81 7 48 7 92 3 46 3 04 4 25 5 27 1 41 4 49 3 81 7 91 6 05 7 21 1 71 1 82 7 96 1 86 0 66 9 29 7 21 6 89 9 42 4 87 2 41 0 84 8 33 8 59 7 71 3 38 3 43 2 24 3 12 5 22 2 13 32 7 86 3 52 2 77 9 36 8 69 1 42 9 63 64 4 47 6 51 3 94 6 51 3 84 5 22 1 55 2 68 92 3 19 32 7 35 25 44 2 94 9 29 8 91 1 14 66 61 9 61 4 95 8 72 1 95 3 74 0 54 6 31 8 22 4 72 9 39 0 02 4 11 2 95 5 92 4 52 8 82 27 94 0 28 7 05 5 46 1 22 5 34 6 05 2 48 8 92 8 26 1 92 2 67 0 36 2 54 5 46 7 42 52 61 6 76 9 51 8 82 0 98 22 8 33 0 64 8 88 81 94 8 75 7 82 88 0 86 4 53 9 16 85 1 82 2 35 4 13 0 94 3 81 0 41 4 61 6 13 1 15 3 37 5 97 36 53 4 06 4 05 0 91 71 8 61 8 42 0 83 9 24 2 71 9 02 0 26 0 86 2 41 2 43 2 46 98 7 33 1 47 3 36 21 2 39 0 82 0 48 4 63 6 31 8 35 9 06 6 95 6 74 9 47 8 18 2 37 6 85 7 95 3 95 7 18 2 98 9 59 9 88 4 85 3 15 6 55 6 97 2 39 1 07 9 23 0 43 4 14 4 16 7 23 6 73 9 86 1 76 2 26 8 74 9 56 4 38 06 5 45 1 29 62 9 54 6 13 8 76 2 34 5 69 1 87 9 94 2 59 3 63 3 43 4 29 4 39 46 0 74 5 99 6 39 5 91 4 12 5 82 3 79 1 68 7 52 4 05 4 23 8 38 4 32 4 96 4 14 2 82 8 03 8 64 3 93 3 94 1 97 6 68 6 82 5 41 5 44 4 07 6 74 1 05 69 7 39 4 25 7 47 0 65 9 38 3 02 7 65 6 44 2 47 8 68 6 76 1 34 7 09 8 37 7 96 9 47 1 74 1 75 2 38 2 64 9 19 2 44 6 92 3 97 6 22 6 29 3 98 1 48 4 45 9 26 0 95 3 23 9 07 4 98 6 31 4 23 8 98 3 25 0 49 5 85 4 36 9 15 92 7 44 8 23 8 09 7 66 42 6 96 7 61 7 78 9 63 6 19 9 27 6 35 1 31 5 14 7 69 1 37 8 92 6 45 7 04 8 67 7 38 3 18 8 01 0 69 4 04 0 95 3 04 7 46 5 85 0 59 4 78 2 59 2 55 4 83 3 05 2 59 6 03 3 38 4 17 8 08 8 74 6 43 6 56 8 46 2 96 7 07 4 63 5 48 2 74 5 18 8 54 3 58 0 27 9 72 7 24 6 89 0 59 8 83 4 95 0 16 9 36 9 92 0 73 8 23 4 68 4 21 7 53 1 76 6 41 1 23 9 37 0 56 8 57 5 41 6 49 3 45 0 39 6 49 2 61 9 29 9 34 6 78 8 41 8 95 7 34 7 53 7 63 7 82 3 38 3 53 1 67 01 8 71 0 35 7 69 2 37 14 0 71 9 96 8 35 0 68 0 36 2 64 43 5 97 7 84 5 77 7 58 5 43 9 73 3 62 6 65 0 72 3 66 0 13 4 53 1 98 1 99 1 98 4 02 0 32 8 17 6 97 4 55 4 95 8 99 8 65 8 59 5 11 3 23 0 85 4 68 7 74 3 48 9 12 1 73 7 03 2 08 6 93 99 2 24 5 02 2 84 1 43 4 31 1 92 4 22 7 03 8 89 01 7 82 3 52 6 81 5 56 0 57 2 78 9 79 0 12 0 19 2 82 32 1 01 6 65 0 08 5 76 4 75 8 26 5 39 54 9 32 6 35 9 51 3 41 0 94 0 64 1 16 7 33 2 65 1 51 1 01 7 07 0 76 1 64 8 44 9 81 4 73 2 94 7 12 9 93 21 01 5 03 1 06 3 91 2 89 92 7 15 4 47 2 83 2 53 1 51 0 141 4 56 06 1 57 43 13 6 01 7 67 8 86 5 02 2 26 4 98 72 8 99 3 59 7 93 5 16 1 19 3 39 4 68 1 66 6 57 5 37 1 67 3 77 8 52 9 75 5 61 1 41 9 58 1 14 0 16 15 3 53 87 9 59 9 53 3 54 6 25 6 85 1 61 6 36 8 18 7 48 6 05 4 07 7 67 5 65 6 27 4 79 5 51 6 94 7 37 53 0 21 5 74 6 66 6 19 81 8 01 5 86 5 67 64 4 78 8 11 7 33 4 84 0 45 6 17 1 97 5 59 7 47 2 08 5 85 6 66 1 49 6 77 7 29 5 34 9 68 2 88 6 56 2 87 6 16 9 67 6 08 3 84 0 84 3 61 9 83 6 99 7 81 52 9 83 3 84 4 85 6 09 1 72 2 56 5 27 2 23 5 67 3 23 5 06 8 92 4 47 3 85 9 76 1 04 55 1 77 4 29 3 22 79 7 18 7 23 9 95 2 25 7 73 6 27 3 44 7 75 9 81 2 56 0 42 5 04 7 84 2 16 9 03 4 72 1 63 7 72 0 61 9 47 83 1 24 8 01 2 03 6 87 3 69 5 62 5 11 3 09 6 22 8 78 39 7 53 3 17 0 45 2 13 7 28 6 22 1 48 4 51 0 02 3 26 0 25 9 91 5 64 1 86 6 62 3 03 1 89 3 72 1 23 01 9 12 0 51 86 73 7 41 5 35 0 84 3 77 7 73 5 26 5 76 7 86 0 39 2 13 5 83 7 14 3 31 1 55 1 13 3 28 2 21 4 02 4 34 4 66 3 81 3 57 1 24 1 64 3 24 4 94 0 32 0 08 0 69 26 7 7
Weight Matrix (C3)
-1 0 1Row Z-Score
Color Key
Blo
od
Mus
cle Fat
Ski
n
Weight Matrix (C4)
-1 0 1Row Z-Score
Color Key
Tissue Data Analysis (4)
A gene is assigned to a tissue if the tissue receives the largest weight in the ANOVA direction. The gene sets are divided into four tissue subsets.
Tissue Tissue Functional groups (GO: BP_5) pathways
C3 (5205 probe sets)
Blood (2242) Apoptosis (8.7E-8)Cell death (3.7E-7)Protein kinase cascade (4.5E-6)
Natural killer cell mediated cytotoxicity (8.0E-4) GnRH signaling pathway (1.3E-3)T cell receptor signaling pathway (1.3E-3)
Skin (1513) Vasculature development (4.2E-7)Blood vessel development (9.1E-7)Blood vessel morphogenesis (1.8E-5)Organ morphogenesis (8.4E-5)
Focal adhesion (2.1E-5)Regulation of actin cytoskeleton (4.9E-4)
Muscle (799) Cellular protein catabolic process (1.1E-3)Modification-dependant macromolecule catabolic process (2.4E-3)Protein catabolic process (2.9E-3)
Tight junction (1.9E-2)Valine, leucine and isolecine degradation (1.9E-2)
Fat (651) Tissue development (9.3E-3)Icosanoid metabolic process (2.7E-2)Fatty acid metabolic process (4.4E-2)
Valine, leucine and isolecine degradation (3.6E-3) Fatty acid metabolism (4.0E-3)Sulfer metabolism (8.9E-3)
Example: functional analysis on tissue subsets of C3.
Extension to Cross-sectional Time Course Data
• Longitudinal: time course measurements are from the same experimental units• Cross-sectional : time course measurements are not from the same experimental units. Different numbers of measurements are allowed at each time points.
Method for cross-sectional data:
• Assume gene specific variance. No correlations over time points.
• Estimate mean vectors for conditions
• Estimate ANOVA directions based on s
• Estimate gene specific variance by pooling information from all arrays
An Example : Impact of Age on Survival After Burn Injury
• One factor : Died/Survived
• Three time points (age groups)
• Two data sets: (1) early stage data (2) middle stage data
• Question: The impact of age on survival after burn injury.
• The data are cross-sectional
Age group 1 (18-39 year-old)
Age group 2 (40-54 year-old)
Age group 3(>=55 year-old)
Data set 1 (early stage)
Died 8 6 10
Survived 49 34 11
Data set 2(middle stage)
Died 7 5 7
Survived 38 26 7
Impact of Age on Survival After Burn Injury (1) • 1236 (early stage ) and 1171 (middle stage) probe sets are differentially expressed between survival & non survival populations (FDR=0.05).
Early Stage Data
Impact of Age on Survival After Burn Injury (2)
Middle Stage Data
Impact of Age on Survival After Burn Injury (3)
• Weight matrix:
• Weight matrix reflects the impact of age groups for each gene.
AG
2
AG
1
AG
3
9 1 28 3 61 1 9 54 2 41 2 3 41 1 3 88 5 11 1 2 41 1 8 61 0 5 62 5 93 7 41 8 15 4 79 6 01 0 4 11 1 7 35 0 49 8 37 8 81 0 1 11 1 1 53 6 97 9 99 2 21 3 99 7 95 1 85 9 32 1 05 2 58 38 8 21 0 4 31 2 2 61 0 1 52 0 65 8 78 1 68 6 74 4 37 73 6 11 7 61 1 18 2 01 2 0 23 4 81 1 6 63 1 11 17 6 99 0 91 2 0 76 3 31 0 2 89 01 0 8 81 8 51 1 52 0 72 6 98 9 41 0 5 94 96 7 05 7 01 0 4 21 1 7 01 25 1 42 2 01 4 56 0 41 5 75 3 72 0 11 2 2 51 0 8 33 5 91 2 2 81 2 0 89 9 31 1 8 99 9 84 63 7 16 8 13 9 41 2 1 18 7 49 9 93 8 24 0 67 0 61 0 6 04 4 01 0 3 69 2 71 4 79 5 91 1 3 77 8 09 2 45 8 97 8 72 6 45 5 69 6 87 17 3 63 2 51 0 92 8 44 0 06 7 11 9 01 9 71 1 81 1 92 6 65 7 23 8 91 1 3 68 5 65 59 5 01 1 1 81 1 9 15 9 09 2 98 1 52 8 21 0 9 05 4 82 4 21 0 6 41 08 12 9 36 9 94 9 95 9 62 51 1 21 91 1 1 36 75 6 75 4 38 0 27 39 4 81 6 15 1 79 7 56 4 94 8 31 1 8 03 4 41 0 3 51 0 0 44 5 19 1 77 1 96 2 19 9 64 7 51 0 9 34 7 38 2 53 6 86 0 87 5 51 3 81 0 1 41 2 0 52 5 21 0 8 51 0 7 16 6 21 0 5 48 7 04 5 21 8 77 2 83 487 95 4 43 71 1 2 98 9 92 4 95 5 211 1 0 15 6 51 1 4 222 8 13 2 07 4 66 2 71 2 1 61 0 0 51 1 5 37 4 31 2 2 71 0 3 757 41 4 44 4 78 1 91 3 57 0 31 1 3 41 7 84 7 78 3 12 0 47 6 835 4 21 1 5 11 3 61 5 81 0 0 11 0 2 45 11 1 8 11 6 87 4 77 4 86 8 56 1 72 67 7 92 82 7 93 04 72 9 79 3 31 4 82 2 78 7 69 33 87 5 03 11 0 5 18 99 3 13 94 4 91 7 07 66 0 53 3 11 1 2 11 0 9 21 5 18 8 36 2 25 8 15 7 91 4 95 83 0 28 02 0 01 1 2 35 31 0 3 44 51 0 7 26 0 63 8 01 7 94 5 32 1 83 4 63 0 81 2 3 11 8 92 4 72 3 21 1 0 86 7 88 22 0 36 0 91 2 81 0 1 66 7 54 1 02 3 32 8 54 0 41 1 0 44 9 81 1 0 73 9 37 0 11 0 0 31 1 6 31 6 71 59 41 48 74 3 72 0 91 32 7 23 8 42 2 54 9 21 1 7 541 83 0 32 5 82 27 5 96 7 21 3 12 3 83 0 48 3 31 6 45 4 13 58 6 69 0 27 52 75 1 16 64 8 71 0 8 66 8 41 1 74 3 67 0 58 1 33 4 96 54 7 24 4 65 3 62 2 94 9 11 0 6 73 3 42 2 85 2 09 19 6 76 4 51 1 61 2 62 1 62 38 0 39 7 28 81 0 69 4 42 6 01 0 1 99 61 3 41 0 6 23 1 81 8 31 2 79 3 94 14 8 51 0 3 05 71 7 73 5 61 0 0 21 1 31 2 32 5 11 75 0 16 2 63 8 87 21 1 8 34 0 23 9 94 6 07 7 078 9 78 3 47 5 48 2 15 7 55 2 19 8 96 1 12 0 81 1 1 17 4 41 1 5 71 0 5 57 2 21 0 6 81 2 15 1 53 9 54 1 76 9 31 1 9 26 1 26 5 36 9 64 3 08 8 09 7 86 3 51 1 9 89 0 55 2 44 8 28 5 72 1 23 0 73 2 86 7 71 0 4 82 1 12 6 88 3 91 1 9 04 4 56 2 89 77 8 37 8 98 63 7 65 8 82 9 51 1 3 23 0 04 1 59 2 35 8 59 8 11 5 46 0 72 5 66 5 84 0 53 2 14 0 16 4 42 2 11 9 58 2 77 8 18 5 82 6 27 1 02 5 53 4 55 3 91 0 5 84 8 02 3 75 4 61 7 42 0 53 3 01 0 7 47 2 97 9 46 1 67 8 21 0 9 41 1 8 41 1 9 43 4 31 2 1 46 0 09 0 78 7 11 0 3 21 0 8 41 1 6 49 8 29 8 71 1 8 59 4 03 5 89 5 39 6 52 8 67 6 51 0 7 99 9 21 2 2 28 8 99 8 42 5 31 0 8 06 4 67 2 61 1 5 51 1 6 82 3 69 2 67 9 86 6 84 9 56 07 6 61 2 3 26 5 92 9 11 2 1 21 2 2 01 1 2 01 0 5 39 6 68 2 47 6 48 6 31 0 2 66 6 61 0 2 91 2 94 1 81 9 95 3 04 8 64 9 31 1 4 51 0 3 99 5 16 4 79 4 25 9 29 6 29 24 3 97 1 49 1 49 7 47 1 35 5 75 8 39 7 03 7 21 1 4 31 1 0 02 7 54 6 58 2 36 9 78 0 07 3 59 3 27 5 11 1 7 61 2 3 61 2 3 59 3 41 1 5 67 7 47 7 65 6 19 9 15 4 91 1 8 72 4 54 3 33 9 01 0 8 72 7 61 1 0 61 1 4 96 4 25 0 76 6 91 1 5 91 2 2 91 9 36 6 11 0 4 41 2 2 11 1 1 41 0 2 21 1 2 77 2 71 1 6 23 2 38 6 97 2 01 1 0 57 3 11 0 0 99 3 09 7 16 0 38 4 71 0 4 75 3 57 2 58 1 08 8 41 1 0 91 1 1 29 0 01 2 0 16 5 01 1 4 68 1 46 9 21 0 7 33 2 71 1 0 35 6 91 0 4 55 9 95 3 28 5 36 5 65 8 61 2 1 04 6 97 0 73 8 67 0 92 6 79 4 39 8 86 7 61 1 3 06 43 6 04 6 65 1 38 0 84 2 51 0 3 34 5 61 0 8 15 2 71 0 9 74 9 68 7 29 2 81 1 1 05 9 48 3 72 8 88 7 73 0 68 4 61 0 4 98 4 35 1 09 1 05 2 93 1 53 3 38 6 88 0 65 0 27 2 16 3 71 1 1 63 7 59 9 41 1 5 81 2 1 87 4 04 3 16 3 22 6 59 5 55 2 27 7 57 3 83 8 58 6 01 1 6 19 81 0 54 0 88 6 17 8 51 1 6 51 6 66 9 48 6 51 0 9 61 1 3 97 1 69 2 05 1 96 2 46 28 4 93 3 67 3 94 6 19 1 82 2 64 5 43 1 99 4 69 0 45 8 41 0 9 98 41 2 54 6 32 7 83 5 75 5 58 8 67 1 57 4 23 9 25 0 31 6 95 5 13 2 91 6 21 2 0 33 5 56 3 93 6 34 1 25 5 34 9 49 3 69 0 82 2 44 1 97 4 91 1 8 88 8 72 9 07 0 02 5 74 3 44 5 03 4 24 8 14 5 53 1 79 91 5 32 3 91 1 4 46 4 16 9 13 1 65 4 55 8 26 1 97 5 31 7 35 7 73 5 07 6 06 8 31 0 9 52 3 08 3 23 3 23 3 72 7 41 1 9 62 1 74 7 01 0 0 61 1 3 34 7 81 0 9 82 5 09 1 56 3 06 5 79 1 33 5 11 0 7 71 0 6 64 2 76 8 61 8 07 0 81 2 0 47 6 32 1 58 1 21 9 25 9 71 1 7 89 8 61 1 7 99 7 36 9 81 1 2 53 6 69 1 13 2 61 1 5 06 8 29 1 68 1 18 5 95 28 4 21 0 1 01 2 2 32 7 19 6 38 4 41 0 6 36 4 31 1 6 05 9 15 97 2 45 2 31 1 4 07 2 39 6 91 0 5 03 9 61 0 6 17 9 51 2 0 62 9 44 7 96 3 16 1 56 3 68 9 67 9 36 8 85 0 87 1 71 1 7 75 7 61 1 4 11 0 3 81 1 9 36 6 78 6 28 9 29 4 52 7 05 0 54 8 47 9 09 2 59 9 54 5 87 4 51 0 0 79 6 14 6 47 3 79 5 27 5 21 5 64 3 81 2 1 71 0 0 05 7 31 1 8 21 0 26 9 58 0 57 0 41 1 5 41 2 1 37 5 88 3 51 0 5 76 32 0 21 0 2 59 0 32 1 36 6 08 7 96 3 43 7 94 5 76 8 79 5 88 2 99 5 65 2 81 1 1 91 6 02 8 02 4 84 1 44 8 91 1 1 71 0 37 1 21 0 87 3 24 6 21 0 03 1 41 9 41 1 47 9 23 9 75 1 22 5 44 8 81 4 19 4 91 8 27 4 12 4 13 0 94 2 91 8 84 2 81 0 5 28 7 867 8 69 1 96 1 01 1 9 91 1 3 51 7 51 1 0 27 9 72 6 38 7 31 1 7 26 5 22 3 18 1 81 0 7 68 53 4 71 0 11 6 34 2 07 1 15 01 8 65 4 01 9 84 0 36 81 0 1 85 6 36 4 82 9 81 0 1 72 4 66 5 17 6 13 5 37 5 76 1 41 1 4 79 6 41 3 31 0 6 98 4 51 5 56 6 31 0 1 39 9 78 0 13 1 08 1 73 5 45 3 16 1 89 4 71 5 01 0 8 93 7 01 6 53 8 11 0 0 81 2 3 02 2 23 0 52 6 15 45 5 83 3 96 2 95 0 63 4 11 9 13 5 27 7 28 3 02 7 36 4 03 6 26 7 31 1 6 73 1 35 5 97 3 04 4 81 1 7 43 2 21 0 2 71 2 48 4 81 0 8 26 6 43 2 47 83 6 79 2 11 0 3 12 8 32 9 28 9 31 0 7 05 5 41 0 1 26 9 02 47 6 71 2 06 5 42 8 91 0 47 9 61 1 5 26 11 0 4 08 0 48 2 28 4 09 0 16 5 57 7 81 7 18 3 81 0 2 32 9 91 1 9 73 8 72 8 75 6 81 3 08 5 25 8 05 9 55 9 81 2 3 34 4 23 4 03 7 72 04 3 29 4 16 0 26 2 34 0 93 6 58 7 57 7 39 9 04 1 61 0 7 51 1 6 99 3 55 7 86 3 89 8 51 1 2 66 2 09 5 78 9 17 1 81 9 69 3 85 6 49 7 71 0 9 13 9 88 6 43 3 51 2 2 49 3 76 8 02 7 79 5 43 0 11 2 27 0 25 7 41 2 0 07 7 78 8 87 6 21 1 2 81 4 24 5 95 5 01 2 0 91 7 24 2 68 9 57 3 31 1 7 16 0 16 8 98 5 54 0 74 9 08 9 84 9 73 7 84 27 8 43 3 83 6 41 1 4 81 4 04 4 19 8 08 2 89 0 64 2 24 4 44 2 15 3 48 4 11 0 6 51 2 1 94 7 41 1 2 21 4 65 3 31 0 4 64 1 38 8 53 24 3 55 1 61 63 37 3 47 01 0 2 01 0 2 15 63 1 22 1 92 4 44 096 2 51 1 04 7 15 7 17 7 15 6 64 42 11 8 43 8 31 0 75 6 22 1 42 4 38 0 91 5 29 54 1 11 3 72 4 08 0 74 87 5 61 0 7 81 2 1 54 32 3 44 7 66 7 46 7 98 5 02 9 63 9 12 3 55 6 07 9 18 2 61 3 25 3 84 6 86 6 51 5 94 6 79 7 63 7 35 2 68 8 15 0 03 68 9 04 2 35 0 98 5 42 2 31 4 36 1 31 1 3 16 92 9
Weight Matrix (Early Stage)
-1 0 0.5 1Row Z-Score
Color Key
AG
3
AG
1
AG
2
6 3 29 6 69 61 0 4 39 9 21 1 6 35 9 39 9 61 0 8 83 1 35 2 62 0 14 1 85 5 72 0 48 4 21 0 1 54 3 56 3 59 1 84 0 87 5 21 0 4 67 2 11 0 8 16 0 99 4 32 7 35 8 11 1 5 11 1 1 58 1 51 0 9 39 9 07 8 56 2 66 0 79 3 07 5 91 0 1 11 2 01 1 4 08 5 01 1 1 27 8 47 1 47 2 57 0 31 1 2 51 7 65 0 42 2 51 1 2 31 1 3 51 0 6 99 2 09 8 81 1 5 26 4 41 0 2 41 0 8 59 1 47 7 37 9 28 9 14 0 55 6 91 0 2 15 5 41 0 7 41 2 16 5 24 2 42 1 85 0 33 8 18 6 41 1 3 11 1 3 23 3 35 5 55 9 41 1 2 68 0 88 2 37 7 41 0 0 35 5 99 8 24 2 19 2 46 7 35 6 36 7 64 4 81 2 41 0 5 18 5 23 8 25 84 8 27 8 71 0 9 71 0 2 37 1 36 2 31 6 41 1 04 7 846 5 84 3 89 8 08 3 63 05 8 25 42 4 68 0 53 0 54 1 68 9 94 7 11 47 3 56 1 28 0 49 1 91 0 3 88 3 45 5 01 8 11 0 7 18 1 88 6 71 0 1 78 6 56 2 12 6 08 3 76 0 23 3 74 3 11 0 8 34 4 74 2 86 2 28 7 47 5 43 0 71 0 8 69 8 42 3 38 1 17 0 46 4 87 59 2 38 2 17 6 65 5 16 0 81 1 4 24 7 47 6 95 1 63 5 05 55 3 06 6 02 1 71 1 5 61 4 51 0 3 29 7 94 5 12 5 68 36 5 04 5 85 7 81 8 26 1 54 2 74 6 11 9 21 05 6 29 5 21 5 03 9 19 2 26 8 95 2 51 1 6 05 6 11 1 6 58 5 71 6 03 2 25 31 6 61 5 31 1 71 1 5 36 1 98 89 08 57 1 88 6 91 8 85 9 53 8 78 3 51 5 11 1 3 82 1 68 7 83 6 09 5 89 91 1 1 72 8 52 8 63 6 87 4 08 4 47 4 26 61 0 5 24 73 4 27 1 67 28 5 64 1 26 4 78 9 42 4 37 7 23 82 1 38 8 17 68 4 36 0 51 0 5 69 9 43 38 1 04 7 51 1 4 62 3 17 6 21 0 8 94 6 46 9 09 5 55 6 59 0 41 0 9 53 3 67 4 85 7 99 7 43 8 37 6 76 6 26 6 51 5 98 8 23 15 3 95 3 71 0 7 58 2 86 97 3 46 7 12 9 07 2 82 0 98 5 94 0 91 0 59 7 11 8 08 7 39 4 67 8 68 5 56 2 78 0 71 0 2 28 6 29 6 21 0 4 15 7 03 1 05 4 79 5 69 5 17 0 91 9 41 1 0 94 2 31 1 4 81 0 8 07 7 56 2 01 0 1 41 1 6 98 4 81 0 5 77 1 71 0 4 81 7 07 2 24 7 99 7 37 7 18 8 88 3 12 0 62 1 12 0 31 1 2 11 0 72 5 95 69 3 41 0 9 82 7 44 9 27 9 99 37 1 02 4 96 8 16 8 51 9 58 2 09 0 38 7 61 1 4 76 8 26 1 01 1 2 97 8 81 1 5 78 5 86 0 35 8 46 2 88 4 61 0 1 09 1 61 0 3 38 4 71 1 5 09 1 11 0 8 79 5 43 7 68 4 98 1 69 1 36 4 17 9 62 9 35 3 31 0 7 95 2 95 5 21 0 9 48 8 91 0 0 21 1 0 38 9 21 0 2 06 9 78 6 63 99 59 6 31 0 5 32 3 67 7 03 9 21 4 11 0 0 62 6 23 2 59 0 71 97 7 97 8 06 7 51 7 95 1 37 0 84 7 71 6 23 7 54 0 79 4 49 8 91 0 6 72 2 13 4 56 6 66 1 75 6 41 0 17 3 39 9 51 9 32 1 03 3 11 0 3 92 1 98 3 82 11 0 4 75 1 19 8 64 6 76 7 05 5 81 4 42 8 03 8 51 0 2 68 13 5 88 7 26 1 41 1 1 98 4 01 1 6 44 0 44 2 65 0 77 5 18 01 0 1 93 5 93 7 96 4 61 0 9 61 3 32 5 83 3 56 0 66 1 18 5 45 1 76 6 77 01 0 0 04 6 85 2 08 6 39 0 61 3 255 8 87 2 73 5 57 0 13 2 18 0 61 5 82 2 65 7 25 2 48 2 53 1 63 4 33 42 3 09 0 84 06 5 46 8 03 6 55 8 33 2 36 4 31 32 0 83 0 46 3 47 4 56 3 06 5 34 4 42 0 21 8 41 7 46 4 01 1 55 4 66 22 3 88 7 04 57 2 42 7 25 9 18 98 1 24 36 13 8 86 6 13 3 41 1 6 87 2 34 3 24 8 74 6 61 1 18 7 11 1 3 62 8 73 1 74 1 99 0 01 0 91 0 6 12 7 04 4 67 97 2 99 2 82 2 04 5 99 3 98 62 5 59 26 4 91 0 3 49 44 1 07 77 6 14 12 8 32 4 45 3 81 14 0 04 2 01 0 7 72 6 78 7 76 9 53 6 38 2 78 5 19 9 81 2 86 5 76 81 4 85 7 31 1 5 55 1 07 8 21 1 7 01 0 7 06 5 18 0 03 7 15 3 43 5 31 0 5 83 9 74 9 63 8 03 4 08 0 17 9 09 2 61 0 4 05 0 21 6 54 0 39 76 6 47 7 66 3 63 2 71 0 6 25 4 81 0 6 37 4 93 5 67 9 15 1 25 4 49 7 83 1 54 6 31 1 2 04 8 17 0 21 0 2 92 3 59 0 14 9 76 2 42 9 63 5 42 4 13 9 08 73 2 97 39 9 18 1 99 0 96 6 84 3 34 4 91 4 63 7 75 4 95 03 6 78 2 25 9 81 0 6 44 65 0 58 1 77 6 89 4 55 3 26 0 12 6 83 4 91 81 0 1 89 6 51 1 0 78 29 16 5 61 0 0 16 8 46 7 99 5 92 96 9 31 0 5 47 5 32 6 51 0 1 27 9 52 7 55 94 5 24 6 57 5 01 1 0 85 6 01 1 3 01 1 2 45 5 39 7 61 7 31 1 5 49 6 76 3 81 1 96 9 89 6 81 1 4 33 7 21 0 1 67 4 42 8 23 9 83 69 2 92 4 73 6 46 1 67 3 01 0 4 48 8 01 1 1 41 3 52 4 55 3 54 8 07 9 41 1 61 7 51 0 4 23 9 53 9 94 1 19 85 8 02 8 14 5 45 27 3 18 8 44 5 08 4 56 05 1 42 76 3 34 1 71 1 3 43 8 62 6 61 2 36 33 8 45 0 14 5 72 3 43 5 74 3 73 3 95 2 83 1 82 0 05 7 12 4 82 1 47 6 52 7 97 0 57 0 01 1 1 34 9 02 5 29 4 14 8 62 5 71 65 6 61 0 2 59 1 21 2 21 0 67 0 77 2 68 3 22 2 23 0 09 1 77 49 5 05 4 59 7 04 3 05 9 04 1 55 4 31 0 5 025 11 0 7 61 1 6 11 7 82 4 05 6 76 75 1 83 3 21 1 4 93 59 6 07 5 71 9 83 1 97 87 3 62 7 74 6 04 6 92 59 3 21 4 97 6 32 7 83 1 11 2 51 0 4 52 9 53 6 67 7 71 1 0 54 6 26 3 79 5 32 7 16 9 94 8 81 1 2 72 2 49 4 81 0 6 01 0 06 3 12 66 0 09 0 54 8 95 0 67 1 16 0 41 5 77 5 51 6 91 5 51 4 02 8 88 8 73 3 08 3 99 4 06 2 57 4 13 7 45 6 81 0 0 96 2 91 1 1 89 9 31 1 4 53 0 38 9 51 0 3 59 9 91 0 5 93 0 27 5 61 1 4 13 7 89 5 71 9 03 4 49 3 34 8 36 9 61 5 21 1 1 64 5 66 5 99 0 27 4 32 86 3 91 9 61 0 0 46 7 816 9 11 1 2 28 4 15 2 29 7 594 9 41 5 61 0 48 9 74 3 47 2 02 2 93 4 61 1 0 47 7 84 9 96 4 21 3 888 0 94 0 15 0 82 2 76 8 32 7 66 5 51 1 0 14 8 51 4 79 8 52 5 07 9 31 0 8 41 0 8 28 1 49 6 43 9 62 6 47 4 61 2 93 4 85 2 12 0 53 6 95 2 37 1 21 1 4 41 1 7 11 1 5 81 0 2 71 0 3 78 8 53 4 71 0 6 52 3 97 0 61 8 71 1 81 9 92 0 76 7 29 4 28 8 69 3 71 0 4 91 1 5 91 6 14 4 52 8 49 7 25 1 52 8 94 5 36 9 29 2 15 5 61 0 1 35 0 03 8 91 0 2 84 22 9 91 3 71 0 81 3 63 2 81 0 3 12 6 14 2 25 7 61 77 8 93 2 46 4 51 0 9 21 0 9 97 9 88 7 97 5 82 6 33 2 08 9 82 9 11 0 6 81 0 7 81 23 9 41 4 38 6 01 0 38 0 22 4 29 1 04 8 45 7 71 9 11 1 1 01 0 0 53 1 45 3 69 3 61 0 9 161 1 3 97 4 78 0 37 3 94 84 3 93 7 02 9 88 2 93 0 66 6 97 3 82 9 71 1 0 671 1 0 03 5 13 5 24 9 81 0 7 38 41 52 44 93 0 88 2 41 1 3 71 0 0 79 9 75 1 96 1 31 1 1 12 5 14 3 62 5 44 4 24 9 52 2 88 9 34 7 01 3 17 8 16 8 81 8 54 48 1 31 1 6 21 2 63 3 81 1 39 1 56 51 0 7 26 9 49 2 71 0 6 61 7 71 1 6 71 8 91 0 3 04 2 91 1 3 33 0 15 9 61 3 01 6 87 1 93 9 32 2 39 7 72 05 7 44 5 56 8 79 3 18 7 51 3 45 8 71 2 71 0 5 51 7 27 3 72 9 48 9 69 8 75 9 29 4 77 6 05 2 78 8 39 8 19 4 96 41 3 98 6 18 3 31 1 0 22 22 3 27 8 33 21 8 67 15 9 71 6 31 0 26 7 72 31 1 45 79 6 15 7 53 0 91 5 44 1 41 7 18 9 03 6 23 72 3 73 7 39 3 836 8 64 9 39 6 93 4 15 8 68 5 39 2 53 2 65 8 97 1 59 8 31 1 6 66 6 31 1 27 6 44 7 24 0 67 3 21 4 28 2 64 7 34 9 11 0 3 62 5 39 3 51 8 32 6 95 0 97 9 71 0 9 01 1 2 81 6 74 4 35 3 13 1 26 1 88 3 04 4 12 9 24 4 05 4 16 7 44 2 55 8 55 4 24 1 31 9 74 0 22 1 53 6 11 0 0 85 9 92 1 25 4 04 7 68 6 8
Weight Matrix (Middle Stage)
-1 0 0.5 1Row Z-Score
Color Key
First Eigen Gene (Early Stage)
AG1 AG2 AG3
0.5
0.6
0.7
0.8
First Eigen gene (Middle Stage)
AG1 AG2 AG3
0.3
0.4
0.5
0.6
0.7
• The first right singular vector of W (‘first eigen-gene’) reflects the impact of age on the gene set.
• Early data: age group 2 (40-54 yo)
• Middle data: age group 2 (40-54 yo) and 3 (>=55 yo)
Impact of Age on Survival After Burn Injury (4)
The result coincide with the reported increasing death rate in burn patients over 48 year-old (7.3 time more likely to die after burn injury) Some significant pathways:
Early Stage Data
Middle Stage Data
Summary
• A novel approach for analyzing time course multi-factor expression data
(1) Classify genes into different gene sets based on factor effects, suited for explorative study (2) The estimated ANOVA directions capture gene specific response features: response timing and response pattern
• Applications
(1) Burn + Age (pediatric/adult), time course data (2) Burn + Gender, time course data (3) Burn + Tissue (early stage) (4) Age impact on adult survival (early stage & middle stage) (5) Survival + Gender, time course data
• Results are available:
http://gluegrant1.stanford.edu/~DIC/burn.html
Acknowledgements
• Professor Wing Wong
• Weihong Xu, Wenzhong Xiao from Davis lab
Thanks!
