dChip Tutorial
Feb 13, 2008
Dana-Farber Cancer Institute
Department of Biostatistics and Computational Biology
Cheng Li
Department of Biostatistics and Computational Biology
Harvard School of Public Health / Dana-Farber Cancer Institute
Human chromosomes
1
Tumor genome alterations (SNB-75 cell)
NCBI SKY database
Different types of alterations
Nature, 20 Oct 2005
2
Single nucleotide polymorphisms (SNPs)
Jen Philpott
Genotypes of a SNP
GG
TG
TT
3
Affymetrix oligonucleotide microarray
Affymetrix Inc.
Affymetrix oligonucleotide microarray
Affymetrix Inc.
4
Affymetrix oligonucleotide microarray
Affymetrix Inc.
Array image
5
Affymetrix human SNP microarray
Affymetrix Inc.
From array image to genotype calls
6
Loss of heterozygosity (LOH)
A B --SNP
A A
A
A
A A
A A
TSG: Tumor suppressor gene
Devilee et al. 2001
Making LOH calls using SNP array
7
1648
1648t
1395
1395t
128
128t
2107
2107t
2141
2141t
2171
2171t
289
289t
1187
1187t
1007
1007t
1143
1143t
1599
1599t
1937
1937t
2218
2218t
38_march
38_march_t
38_may
38_may_t
1395_feb
1395_feb_t
1395_june
1395_june_t
XO
X3
X4
X5
NA02101B
NA03226
BT474
UACC812
MCF7
1648
1648t
1395
1395t
128
128t
2107
2107t
2141
2141t
2171
2171t
289
289t
1187
1187t
1007
1007t
1143
1143t
1599
1599t
1937
1937t
2218
2218t
38_march
38_march_t
38_may
38_may_t
1395_feb
1395_feb_t
1395_june
1395_june_t
XO
X3
X4
X5
NA02101B
NA03226
BT474
UACC812
MCF7
SNP genotype call view in dChip
A
M
A
M
A
F
A
F
S
M
S
M
S
M
S
M
S
M
S
M
Retention
S
M
AB
S
M
S
F
B
F
S
F
B
F
Loss
B
M
B
M
B
F
B
F
B
F
BB or B
B
F
B
M
B
M
B
F
B
F
B
F
B
F
B
F
Non-info
B
F
B
M
AA or A
B
M
B
M
B
M
MF MF F MMF M
AAAAAAAAA
No Call
Observed LOH calls from pairs
MF MF F MMF M
AAAAAAAAA
No call
8
Hidden Markov Model for inferring LOH
Go to: LD
Beroukhim et al. 2007
LOH from paired vs. LOH from only tumor
9
LOH score from prostate tumor samples
Beroukhim et al. 2007
2087
44
515
366
1171
2347
193
2122
78
1648
1993
95
1672
1819
2887
1395
2009
33
827
2052
1963
1607
289
970
2171
128
2195
2107
2126
1450
209
1184
2141
Clustering samples and chromosomes
Chro All
A A A a N A A A A A A S S A N A A S N M S S S S S S S S L S S S S
type
5
10
12
18
19
3
8
20
21
15
16
13
17
11
9
22
7
14
1
4
X
2
6
10
Correlate LOH data with expression data
B56
B11
B38
B33
B45
B21
B81
B73
B95
B52
B76
B41
B74
B22
B92
B40
B63
B25
B44
B13
B23
B24
B35
B14
B79
B80
B51
B04
Correlate LOH data with expression data
n
D
I
n
n
n
p
n
D
I
n
n
p
w
n
D
I
n
n
n
p
n
D
I
n
n
n
n
n
D
I
n
n
l
p
n
D
I
n
n
n
p
p
D
I
p
p
n
n
p
D
I
p
p
n
n
p
D
I
p
p
n
n
n
D
I
p
p
n
n
p
D
I
p
p
n
n
p
D
I
p
p
l
n
p
D
I
p
p
n
n
n
D
I
p
l
n
n
p
D
I
p
p
n
n
n
D
I
p
p
n
n
n
D
I
n
n
p
p
n
D
I
n
n
p
p
p
D
I
p
l
n
n
n
D
I
p
n
p
n
p
D
I
p
l
n
n
p
D
I
p
n
n
n
p
D
I
n
n
l
n
n
D
I
n
n
p
p
p
D
I
n
n
p
p
p
D
I
p
p
n
p
p
D
I
n
n
p
p
p
D
I
l
l
p
n
lymph nodes
Tumor type
MBR grade
ER
PR - review
HER-2 assessment
p53 impox
3
5
92
6
_s_
at
3
4
09
4
_i
_
a
t
3
4
09
5
_f _
at
3
1
31
5
_a
t
3
5
53
0
_f _
at
3
4
10
5
_f _
at
3
5
56
6
_f _
at
3
8
19
4
_s_
at
3
5
59
0
_s_
at
3
7
86
4
_s_
at
4
1
82
7
_f _
at
3
3
27
3
_f _
at
3
3
27
4
_f _
at
3
7
63
7
_a
t
3
1
58
6
_f _
at
3
4
09
8
_f _
at
3
7
00
6
_a
t
3
3
50
0
_i
_
a
t
3
3
49
9
_s_
at
3
3
50
1
_r _
at
3
9
95
9
_a
t
1
4
03
_
s_
a
t
1
4
05
_
i
_a
t
3
4
21
0
_a
t
3
7
02
3
_a
t
3
7
21
9
_a
t
1
1
06
_
s_
a
t
4
1
81
9
_a
t
3
6
28
0
_a
t
4
0
01
9
_a
t
4
0
51
8
_a
t
3
6
22
7
_a
t
4
0
51
9
_a
t
3
3
26
1
_a
t
3
9
59
3
_a
t
4
1
72
3
_s_
at
3
2
77
3
_a
t
3
7
68
8
_f _
at
3
9
05
2
_a
t
4
1
16
4
_a
t
4
1
16
5
_g
_
at
3
8
79
6
_a
t
3
9
58
1
_a
t
3
5
73
5
_a
t
3
9
70
1
_a
t
4
1
68
3
_i
_
a
t
3
5
17
7
_a
t
4
1
21
9
_a
t
3
8
25
2
_s_
at
3
8
25
3
_a
t
3
8
24
1
_a
t
3
8
82
6
_a
t
4
0
61
8
_a
t
3
4
78
0
_a
t
3
1
85
9
_a
t
3
2
90
5
_s_
at
3
4
98
5
_a
t
3
8
77
2
_a
t
2
8
7_
a
t
3
6
85
1
_g
_
at
3
6
85
2
_a
t
3
8
63
4
_a
t
1
4
61
_
at
3
9
69
6
_a
t
3
2
60
2
_a
t
4
1
14
1
_a
t
3
8
73
2
_a
t
3
3
82
5
_a
t
4
0
07
5
_a
t
3
2
21
5
_i
_
a
t
3
3
88
0
_a
t
1
8
26
_
at
3
6
60
6
_a
t
3
7
6_
a
t
3
7
7_
g
_a
t
4
1
64
2
_a
t
4
0
55
2
_s_
at
3
5
96
4
_a
t
3
8
65
0
_a
t
1
3
96
_
at
3
5
82
4
_a
t
4
0
65
7
_r _
at
3
8
43
0
_a
t
3
8
18
7
_a
t
3
5
79
4
_a
t
2
0
17
_
s_
a
t
3
6
61
7
_a
t
3
3
16
2
_a
t
3
8
69
4
_a
t
3
2
80
2
_a
t
3
2
65
4
_g
_
at
3
1
52
6
_f _
at
3
4
67
7
_f _
at
4
0
67
3
_a
t
4
0
40
9
_a
t
3
7
40
2
_a
t
3
8
08
7
_s_
at
3
5
70
4
_a
t
3
9
71
2
_a
t
3
7
37
7
_i
_
a
t
3
7
55
2
_a
t
4
1
09
6
_a
t
4
1
47
1
_a
t
3
6
57
5
_a
t
3
4
36
3
_a
t
3
8
09
6
_f _
at
3
4
30
4
_s_
at
3
7
69
2
_a
t
2
6
6_
s_a
t
3
2
43
4
_a
t
1
0
39
_
s_
a
t
4
1
29
2
_a
t
4
1
78
8
_i
_
a
t
3
9
01
7
_a
t
4
0
08
8
_a
t
3
6
92
1
_a
t
3
6
69
4
_a
t
3
7
25
9
_a
t
4
0
21
5
_a
t
3
7
54
3
_a
t
3
2
52
7
_a
t
1
2
41
_
at
3
3
82
1
_a
t
3
5
74
2
_a
t
3
9
84
1
_a
t
3
4
86
2
_a
t
3
5
35
2
_a
t
1
8
46
_
at
3
4
19
8
_a
t
3
2
53
1
_a
t
3
4
38
7
_a
t
3
9
71
4
_a
t
3
7
21
5
_a
t
3
5
82
2
_a
t
4
0
50
4
_a
t
4
1
73
3
_a
t
3
8
32
5
_a
t
3
6
13
3
_a
t
4
1
33
5
_a
t
3
4
68
8
_a
t
1
7
25
_
s_
a
t
3
7
14
9
_s_
at
3
8
78
4
_g
_
at
7
0
0_
s_a
t
3
8
78
3
_a
t
9
2
7_
s_a
t
3
4
72
8
_g
_
at
3
5
16
8
_f _
at
3
4
80
0
_a
t
1
9
16
_
s_
a
t
3
5
84
2
_a
t
3
7
14
1
_a
t
3
7
72
3
_a
t
3
3
37
1
_s_
at
4
0
76
6
_a
t
3
8
40
9
_a
t
4
1
09
4
_a
t
3
2
5_
s_a
t
4
1
42
8
_a
t
1
9
33
_
g_
a
t
3
6
49
5
_a
t
3
9
04
5
_a
t
7
8
3_
a
t
7
8
4_
g
_a
t
3
6
10
2
_a
t
3
7
29
7
_a
t
3
6
48
8
_a
t
2
0
42
_
s_
a
t
3
6
78
5
_a
t
3
4
85
9
_a
t
3
8
82
7
_a
t
3
8
25
4
_a
t
3
6
45
4
_a
t
3
5
27
5
_a
t
4
1
78
3
_a
t
1
0
57
_
at
3
8
41
8
_a
t
2
0
20
_
at
3
5
76
6
_a
t
3
3
23
2
_a
t
3
5
21
4
_a
t
3
6
16
5
_a
t
1
7
98
_
at
3
9
68
9
_a
t
3
1
72
0
_s_
at
1
2
8_
a
t
4
0
16
1
_a
t
3
2
30
5
_a
t
7
5
3_
a
t
3
7
89
2
_a
t
3
6
97
6
_a
t
3
8
11
1
_a
t
6
5
8_
a
t
3
9
94
5
_a
t
3
8
11
2
_g
_
at
3
8
42
0
_a
t
7
1
8_
a
t
7
1
9_
g
_a
t
3
2
30
6
_g
_
at
3
2
30
7
_s_
at
3
8
07
7
_a
t
3
9
06
9
_a
t
3
2
53
5
_a
t
3
8
18
1
_a
t
4
0
29
0
_f _
at
3
6
62
7
_a
t
1
7
37
_
s_
a
t
3
6
32
9
_a
t
3
8
14
5
_a
t
1
7
88
_
s_
a
t
3
7
36
3
_a
t
3
1
47
7
_a
t
3
1
79
8
_a
t
3
3
23
6
_a
t
3
8
66
2
_a
t
3
8
01
4
_a
t
6
7
5_
a
t
3
5
93
7
_a
t
4
0
50
5
_a
t
3
9
06
1
_a
t
3
2
81
4
_a
t
3
7
01
4
_a
t
1
3
58
_
s_
a
t
4
2
5_
a
t
9
1
5_
a
t
3
8
43
2
_a
t
1
1
07
_
s_
a
t
3
3
33
8
_a
t
3
3
33
9
_g
_
at
3
8
57
6
_a
t
3
7
75
4
_a
t
4
0
95
1
_a
t
3
1
69
2
_a
t
1
1
04
_
s_
a
t
4
0
06
3
_a
t
3
3
35
2
_a
t
3
7
01
8
_a
t
3
2
60
9
_a
t
2
8
6_
a
t
3
4
30
8
_a
t
3
2
81
9
_a
t
3
6
34
7
_f _
at
3
5
57
6
_f _
at
3
1
52
3
_f _
at
3
1
52
8
_f _
at
4
0
40
7
_a
t
3
6
20
5
_a
t
2
2
7_
g
_a
t
3
6
55
1
_a
t
3
5
75
9
_a
t
3
9
70
7
_a
t
3
3
10
7
_a
t
3
4
31
9
_a
t
3
6
93
3
_a
t
3
3
87
8
_a
t
3
3
90
4
_a
t
3
8
12
4
_a
t
5
7
7_
a
t
3
7
35
5
_a
t
1
9
01
_
s_
a
t
3
3
21
8
_a
t
1
8
02
_
s_
a
t
3
8
99
7
_a
t
3
9
05
6
_a
t
3
2
52
3
_a
t
3
8
78
0
_a
t
4
1
32
2
_s_
at
3
9
02
3
_a
t
4
0
50
9
_a
t
3
2
80
5
_a
t
3
6
65
8
_a
t
3
6
78
0
_a
t
3
8
42
9
_a
t
3
3
36
9
_a
t
3
3
39
9
_a
t
3
7
74
9
_a
t
4
1
45
5
_a
t
4
1
19
3
_a
t
3
9
24
8
_a
t
3
1
88
8
_s_
at
4
0
77
5
_a
t
4
0
14
5
_a
t
9
0
4_
s_a
t
4
0
75
8
_a
t
3
8
43
7
_a
t
2
0
47
_
s_
a
t
3
6
96
5
_a
t
3
9
15
5
_a
t
3
3
82
8
_a
t
3
2
59
7
_a
t
3
8
06
6
_a
t
4
0
6_
a
t
4
0
63
1
_a
t
9
7
7_
s_a
t
3
8
65
7
_s_
at
3
8
61
0
_s_
at
4
1
82
4
_a
t
3
1
51
0
_s_
at
3
7
30
4
_a
t
3
3
41
5
_a
t
1
9
80
_
s_
a
t
1
5
21
_
at
3
9
07
3
_a
t
1
9
85
_
s_
a
t
4
1
18
5
_f _
at
3
5
76
0
_a
t
3
3
35
4
_a
t
9
1
0_
a
t
3
9
35
4
_a
t
3
7
33
8
_a
t
3
8
42
8
_a
t
4
1
29
4
_a
t
3
4
76
1
_r _
at
3
2
52
1
_a
t
3
2
11
2
_s_
at
3
5
93
4
_a
t
1
2
72
_
at
3
3
27
2
_a
t
3
6
12
3
_a
t
3
5
18
5
_a
t
3
6
04
0
_a
t
3
3
87
5
_a
t
3
5
31
1
_a
t
3
9
69
0
_a
t
3
1
88
3
_a
t
3
8
67
8
_a
t
3
9
00
8
_a
t
3
4
71
9
_a
t
3
2
32
9
_a
t
3
5
75
2
_s_
at
8
6
3_
g
_a
t
3
7
15
7
_a
t
1
8
98
_
at
3
4
82
0
_a
t
3
7
03
2
_a
t
3
1
79
2
_a
t
3
7
9_
a
t
1
7
15
_
at
4
0
42
2
_a
t
1
7
41
_
s_
a
t
1
4
99
_
at
1
0
52
_
s_
a
t
4
0
06
0
_r _
at
3
6
13
0
_f _
at
3
3
11
7
_r _
at
3
9
03
4
_a
t
3
8
11
4
_a
t
3
4
40
3
_a
t
3
7
62
8
_a
t
3
2
16
8
_s_
at
3
9
44
3
_s_
at
3
4
79
3
_s_
at
3
2
61
2
_a
t
3
4
41
1
_a
t
3
9
38
2
_a
t
4
1
24
6
_a
t
3
9
01
8
_a
t
3
2
6_
i
_
at
3
9
34
8
_a
t
3
6
68
5
_a
t
3
3
41
2
_a
t
3
5
69
7
_a
t
3
6
68
4
_a
t
2
6
2_
a
t
3
7
76
2
_a
t
3
2
24
3
_g
_
at
1
6
00
4
3_
a
t
3
9
39
6
_a
t
3
7
75
5
_a
t
3
2
90
1
_s_
at
3
8
70
0
_a
t
3
7
72
7
_i
_
a
t
3
9
14
5
_a
t
3
4
82
2
_a
t
3
3
12
1
_g
_
at
3
3
90
1
_a
t
1
8
60
_
at
3
2
84
7
_a
t
3
6
19
7
_a
t
3
1
89
1
_a
t
3
8
15
6
_a
t
3
7
70
1
_a
t
3
4
24
6
_a
t
3
1
73
7
_a
t
1
1
97
_
at
4
0
55
6
_a
t
3
6
93
1
_a
t
3
6
14
5
_a
t
4
1
13
6
_s_
at
3
6
15
9
_s_
at
3
8
80
4
_a
t
4
1
82
3
_a
t
3
7
94
8
_a
t
3
3
87
7
_s_
at
1
1
60
_
at
1
7
89
_
at
1
3
99
_
at
1
0
73
_
at
3
2
82
9
_a
t
3
2
83
1
_a
t
3
9
35
7
_a
t
3
9
81
7
_s_
at
3
8
09
8
_a
t
1
4
95
_
at
3
2
75
5
_a
t
3
5
29
7
_a
t
3
8
75
4
_a
t
4
0
56
7
_a
t
3
8
66
7
_a
t
3
5
29
4
_a
t
3
9
16
7
_r _
at
3
6
79
1
_g
_
at
3
6
79
2
_a
t
4
0
95
3
_a
t
4
1
24
2
_a
t
4
1
45
4
_a
t
2
9
1_
s_a
t
2
0
02
_
s_
a
t
3
3
86
4
_a
t
3
7
21
8
_a
t
3
9
07
0
_a
t
3
3
50
5
_a
t
1
0
42
_
at
3
6
49
6
_a
t
3
9
96
9
_a
t
3
8
32
4
_a
t
3
6
02
7
_a
t
3
7
36
4
_a
t
3
1
49
2
_a
t
3
2
84
3
_s_
at
3
1
86
3
_a
t
3
8
23
3
_a
t
3
7
35
7
_a
t
3
9
35
3
_a
t
5
7
5_
s_a
t
4
0
41
7
_a
t
4
1
18
8
_a
t
3
9
17
5
_a
t
3
4
34
2
_s_
at
2
0
92
_
s_
a
t
3
3
87
6
_a
t
3
4
88
7
_a
t
3
9
47
1
_a
t
3
8
04
1
_a
t
3
6
62
0
_a
t
3
8
39
2
_a
t
2
9
6_
a
t
4
1
69
6
_a
t
3
7
34
8
_s_
at
3
6
09
9
_a
t
3
9
79
3
_a
t
3
2
22
0
_a
t
3
6
65
4
_s_
at
4
0
84
5
_a
t
4
0
61
9
_a
t
8
9
3_
a
t
4
0
33
9
_a
t
4
1
53
1
_a
t
8
9
2_
a
t
3
6
63
6
_a
t
3
6
68
7
_a
t
3
8
68
1
_a
t
3
2
54
4
_s_
at
3
6
20
1
_a
t
3
6
57
8
_a
t
3
7
22
5
_a
t
3
9
37
9
_a
t
4
1
47
0
_a
t
6
6
8_
s_a
t
3
7
34
5
_a
t
4
0
80
3
_a
t
3
7
32
4
_a
t
3
8
43
5
_a
t
4
0
44
1
_g
_
at
3
8
83
9
_a
t
3
8
61
8
_a
t
3
8
47
3
_a
t
3
4
68
4
_a
t
3
8
66
4
_a
t
3
8
84
7
_a
t
1
8
40
_
g_
a
t
4
1
63
2
_a
t
4
0
11
7
_a
t
1
0
55
_
g_
a
t
3
6
10
4
_a
t
4
0
11
5
_a
t
1
3
10
_
at
3
5
30
7
_a
t
3
5
81
8
_a
t
3
6
97
8
_a
t
3
7
89
9
_a
t
4
0
12
2
_a
t
3
5
81
4
_a
t
3
8
41
6
_a
t
3
7
32
5
_a
t
3
7
34
7
_a
t
4
1
51
4
_s_
at
4
0
77
4
_a
t
3
3
15
4
_a
t
1
3
11
_
at
3
6
44
6
_s_
at
4
1
83
4
_g
_
at
3
7
37
3
_a
t
4
0
69
0
_a
t
4
1
45
1
_s_
at
3
5
81
6
_a
t
3
8
99
2
_a
t
3
4
38
3
_a
t
3
8
35
4
_a
t
3
5
71
4
_a
t
8
6
0_
a
t
3
7
26
3
_a
t
3
3
81
9
_a
t
3
7
72
4
_a
t
3
7
67
9
_a
t
3
8
84
0
_s_
at
3
2
77
5
_r _
at
3
8
92
4
_s_
at
2
8
8_
s_a
t
7
7
7_
a
t
3
7
89
0
_a
t
4
0
04
1
_a
t
4
1
14
2
_a
t
3
4
87
8
_a
t
3
9
82
7
_a
t
3
8
42
6
_a
t
4
0
99
2
_s_
at
1
0
31
_
at
4
0
91
5
_r _
at
5
2
7_
a
t
3
9
30
2
_a
t
4
0
34
8
_s_
at
3
9
33
7
_a
t
1
8
84
_
s_
a
t
3
4
73
6
_a
t
1
9
45
_
at
3
7
99
4
_a
t
3
9
02
8
_a
t
3
7
64
0
_a
t
3
5
75
0
_a
t
1
7
1_
a
t
3
6
18
8
_a
t
3
8
01
1
_a
t
4
0
03
6
_a
t
3
9
79
9
_a
t
3
9
11
4
_a
t
3
9
11
9
_s_
at
3
5
06
1
_a
t
4
3
1_
a
t
1
5
68
_
s_
a
t
3
1
48
8
_s_
at
3
4
66
6
_a
t
3
5
13
6
_a
t
3
7
82
3
_a
t
3
4
71
7
_s_
at
1
4
81
_
at
1
4
82
_
g_
a
t
3
9
26
9
_a
t
1
2
69
_
at
1
4
56
_
s_
a
t
3
6
92
7
_a
t
3
7
64
1
_a
t
3
7
54
4
_a
t
3
4
37
8
_a
t
1
4
52
_
at
3
9
16
9
_a
t
3
8
06
5
_a
t
3
8
74
4
_a
t
3
3
85
6
_a
t
3
5
31
6
_a
t
3
9
07
1
_a
t
4
0
86
1
_a
t
3
9
83
9
_a
t
4
1
22
9
_a
t
4
0
64
2
_a
t
3
6
49
1
_a
t
3
8
47
4
_a
t
3
7
67
8
_a
t
3
9
41
0
_a
t
3
4
33
5
_a
t
3
7
18
7
_a
t
3
3
84
9
_a
t
3
5
37
2
_r _
at
3
3
70
5
_a
t
1
7
17
_
s_
a
t
3
7
53
4
_a
t
3
2
81
8
_a
t
3
9
35
1
_a
t
3
4
79
5
_a
t
1
4
94
_
f _
a
t
3
6
68
1
_a
t
4
0
08
2
_a
t
4
0
20
1
_a
t
4
1
04
9
_a
t
2
6
0_
a
t
1
8
5_
a
t
4
1
21
0
_a
t
3
5
17
4
_i
_
a
t
3
3
45
2
_a
t
3
9
26
6
_a
t
3
9
66
5
_a
t
3
6
78
1
_a
t
3
4
26
5
_a
t
4
0
09
5
_a
t
3
6
91
0
_a
t
3
3
89
0
_a
t
2
0
94
_
s_
a
t
1
9
15
_
s_
a
t
4
1
35
4
_a
t
4
0
07
8
_a
t
3
9
03
1
_a
t
3
6
21
5
_a
t
2
7
9_
a
t
2
8
0_
g
_a
t
4
0
43
4
_a
t
3
7
27
3
_a
t
3
5
77
8
_a
t
3
3
83
6
_a
t
2
0
57
_
g_
a
t
2
0
56
_
at
4
2
4_
s_a
t
-3.0
-2.5
-1.9
-1.4
-0.8
-0.3
0.3
0.8
1.4
1.9
2.5
3.0
"lymph nodes" is negative: 6/6 (all: 13/28, PValue: 0.0046)
11
Linkage analysis using SNPs
5026.10_1
5026.10_2
5026.10_3
5026.10_4
5026.10_5
5026.10_6
5026.10_7
Linkage analysis using SNP array
Chro 3
1
ch
ol
e
cyst okn
i n
i
p
r e
prop
r o
t e
n
i
ce
l a
dh
eso
i n mo
e
l cul
e w
t
i h h
om o
o
l g
y
t o .. .
co
nt act n
i
6
3p
. ..
co
nt act n
i
4 s
i of orm
a p
r e
cu
r sor
co
nt act n
i
4 s
i of orm
co
nt act n
i
4 s
i of orm
c p
r e
cu
r sor
b p
r e
cu
r sor
3p
. ..
KI AA
14
97 p
r o
t e
n
i
SE
T do
m ai
n a
nd m a
r n
i er t r a
nspo
sa
se . . .
" n
i ost
i o
l 1
, 4
, 5
- tr p
i ho
sp
ha
t e recep
t o
r ,
.. .
1
2
2
2
1
2
Affected
SN
P_
A-15
13
29
2
SN
P_
A-15
11
74
2
SN
P_
A-15
15
06
1
SN
P_
A-15
10
24
4
SN
P_
A-15
15
25
8
SN
P_
A-15
09
53
0
SN
P_
A-15
16
29
7
SN
P_
A-15
14
10
2
SN
P_
A-15
12
76
7
SN
P_
A-15
16
50
4
SN
P_
A-15
18
74
7
SN
P_
A-15
09
32
7
SN
P_
A-15
13
86
9
SN
P_
A-15
19
35
6
di
ff e
r e
nt a
i t ed e
m bryo cho
nd
r o
cyt e e
x. . .
SN
P_
A-15
17
79
6
SN
P_
A-15
10
24
2
SN
P_
A-15
15
09
0
SN
P_
A-15
08
19
9
3p
. ..
" g
u
l t am a
t e recep
t o
r ,
3p
. ..
me
t a
bo
t rop
c
i
7"
LI M
a
nd cyst e
n
i e
- ri
ch d
om a
n
i s 1
po
st r e
pl
c
i at o
i n rep
ai
r p
r o
t e
n
i
hR
AD
18
p
D
K
FZ
P4
34
F0
91 p
r o
t e
n
i
hypo
t h
et c
i a
l p
r o
t e
n
i
FL
J2
24
05
act n
i
rel
a
t e
d prot ei
n 2
/ 3 com p
e
l x sub
u. . .
un
ch
aract e
r z
i ed h
em a
t o
po
e
i tc
i
st em / p. . .
so
u
l t e ca
r ri
er f am y
l
i
6 (ne
urot r a
nsm t
i t er
hi
st a
mn
i e recep
t o
r H
1
3p
. ..
3p
. ..
hypo
t h
et c
i a
l p
r o
t e
n
i
BC
01
50
88
t s
i su
e n
i h
b
i t
i or o
f
m et al
o
l prot ei
n
ase 4
hypo
t h
et c
i a
l p
r o
t e
n
i
MG C
2
77
6
hypo
t h
et c
i a
l p
r o
t e
n
i
FL
J1
10
36
nu
cl
e
op
ori
n 21
0
hi
st o
ne d
ea
ce
t ya
l se 11
" w
n
i g
e
l ss-t ype M M T
V n
i t eg
r a
t o
i n si
te f .. .
hypo
t h
et c
i a
l p
r o
t e
n
i
FL
J3
17
09
so
u
l t e ca
r ri
er f am y
l
i
6 (ne
urot r a
nsm t
i t er
hypo
t h
et c
i a
l p
r o
t e
n
i
LO C
51
24
4
" n
uce
l a
r r e
ce
pt or sub
f a
my
l
i
2,
g
r o
up . . .
hypo
t h
et c
i a
l p
r o
t e
n
i
MG C
2
41
32
bi
o
t n
id
i a
se p
r e
cu
r sor
U
D
P-N
-acet yl
- al
p
ha
- D
- g
al
a
ct osam n
i e: po
y
l .. .
hypo
t h
et c
i a
l p
r o
t e
n
i
BC
00
83
22
de
e
l t ed n
i
a
zo
ospe
r ma
i- k
i
le
ph
osph
ol
p
i ase C
-l
k
i e 2
SN
P_
A-15
15
61
5
SN
P_
A-15
07
77
1
SN
P_
A-15
16
58
2
SN
P_
A-15
13
99
9
SN
P_
A-15
11
56
0
SN
P_
A-15
16
94
7
SN
P_
A-15
07
87
5
SN
P_
A-15
13
34
8
SN
P_
A-15
07
86
0
SN
P_
A-15
17
73
2
SN
P_
A-15
13
08
3
SN
P_
A-15
11
79
9
SN
P_
A-15
13
29
7
SN
P_
A-15
13
17
7
SN
P_
A-15
14
38
9
SN
P_
A-15
14
70
9
SN
P_
A-15
13
43
7
SN
P_
A-15
13
26
4
SN
P_
A-15
13
76
5
SN
P_
A-15
09
16
9
SN
P_
A-15
13
11
0
SN
P_
A-15
08
42
5
SN
P_
A-15
09
53
4
SN
P_
A-15
13
97
5
SN
P_
A-15
08
85
2
sp
eca
i l AT
- ri
c h seq
ue
nce bi
n
di
n
g prot ei
n 1
" p
ot assi
u
m
vol
t ag
e-ga
t e
d ch
an
ne
,
l
SN
P_
A-15
16
00
3
SN
P_
A-15
12
63
1
SN
P_
A-15
10
53
3
su
b. . .
3p
. ..
hypo
t h
et c
i a
l p
r o
t e
n
i
FL
J2
52
00
" R
AB
5A
,
m em b
er R
AS o
ncog
en
e f a
my
l
i "
3p
. ..
r e
t n
i oi
c a
ci
d recep
t o
r -be
t a a
ssoca
i t ed . . .
N
-gl
yca
na
se 1
SN
P_
A-15
14
70
6
SN
P_
A-15
14
82
9
SN
P_
A-15
17
00
9
SN
P_
A-15
14
70
7
SN
P_
A-15
19
25
3
SN
P_
A-15
17
25
8
hypo
t h
et c
i a
l p
r o
t e
n
i
FL
J2
24
19
SN
P_
A-15
10
97
0
SN
P_
A-15
15
67
2
SN
P_
A-15
11
85
7
hypo
t h
et c
i a
l p
r o
t e
n
i
FL
J2
51
57
ub
q
i u
t
i n
i - con
u
j g
at n
i g e
nzym e E
2E 1 (U
B
C
4
/ 5
" t hyr o
d
i
ho
r mo
ne recep
t o
r ,
b
et a ( e
r .. .
SN
P_
A-15
16
10
6
SN
P_
A-15
16
09
6
SN
P_
A-15
08
49
4
SN
P_
A-15
17
82
9
SN
P_
A-15
13
13
3
SN
P_
A-15
13
05
9
SN
P_
A-15
19
62
0
hypo
t h
et c
i a
l p
r o
t e
n
i
LR
P1
5
SN
P_
A-15
15
44
2
SN
P_
A-15
08
02
7
hypo
t h
et c
i a
l p
r o
t e
n
i
FL
J3
26
85
" sol
u
t e carr e
ir f a
my
l
i
4,
sod
u
i m
eo
m esod
erm n
i
bi
carb. . .
SN
P_
A-15
16
64
3
SN
P_
A-15
19
00
9
5-azacyt d
i n
ie n
i d
uced g
en
e 2
" R
N
A b
n
i d
n
i g mo
t f
i,
si
n
gl
e st ran
de
d n
i t e. . .
SN
P_
A-15
11
34
8
SN
P_
A-15
11
57
2
SN
P_
A-15
08
09
5
3p
. ..
" tr a
nsf o
r mn
i g grow
t h f act o
r ,
b
et a r . . .
oxyst e
r o
l b
n
i d
n
i g p
r o
t e
n
i -l
k
i e p
r o
t e
n
i
10
KI AA
00
89 p
r o
t e
n
i
ch
em o
ki
n
e-l
k
i e f act o
r su
pe
r f a
my
l
i
7
ch
em o
ki
n
e-l
k
i e f act o
r su
pe
r f a
my
l
i
6
ch
em o
ki
n
e ( C
- C mo
t f
i) r e
ce
pt or 4
F-bo
x an
d e
l u
ci
n
e-r c
ih r e
pe
at
p
r o
t e
n
i
2
SN
P_
A-15
18
43
3
SN
P_
A-15
09
25
4
SN
P_
A-15
15
04
8
SN
P_
A-15
08
50
5
SN
P_
A-15
11
21
1
SN
P_
A-15
10
37
2
3p
23
prog
r a
m m ed cel
l de
at h 6 n
i t eract n
i g p. . .
SN
P_
A-15
09
51
5
SN
P_
A-15
10
05
4
" cycc
i
l
3p
. ..
3p
. ..
AM P
- reg
ul
a
t e
d ph
osph
op
r o
t e
n
i ,
.. .
src ho
m ol
o
gy t hree (SH
3) a
nd cyst e
n
i .. .
KI AA
07
66 g
en
e prod
uct
e
l u
ci
n
e r c
ih r e
pe
at
(i
n FL
I I) n
i t eract n
ig
" n
it e
gri
n,
a
p
l h
a 9"
H
Y
A2
2 prot ei
n
vi
n
i
l- k
i
le
orga
ni
c cat o
i n tr a
nspo
r t er k
i
le 4
" sod
u
i m ch
an
ne
,
l
vo
t
l a
ge
- g
at ed
,
t ype . . .
WD r e
pe
at
e
nd
osom a
l p
r o
t e
n
i
ch
em o
ki
n
e ( C
- C mo
t f
i) r e
ce
pt or 8
m yo
si
n V
I I A an
d R
a
b n
i t eract n
i g prot ei
n
t ran
sl
a
t o
in f a
ct or
hypo
t h
et c
i a
l p
r o
t e
n
i
FL
J2
05
74
hypo
t h
et c
i a
l p
r o
t e
n
i
MG C
2
67
68
va
so
act v
ie n
i t est n
i al pe
pt d
i e recep
t o
r
ch
em o
ki
n
e bi
n
di
n
g prot ei
n 2
SN
F-1 r e
a
l t ed kn
i a
se
C
G I- 5
8 prot ei
n
3p
. ..
3p
. ..
3p
. ..
3p
. ..
SN
P_
A-15
10
20
7
SN
P_
A-15
15
68
7
SN
P_
A-15
11
75
8
SN
P_
A-15
13
94
4
1
hypo
t h
et c
i a
l p
r o
t e
n
i
D
K
FZ
p3
13
N
0
62
1
zi
n
c f n
i ge
r prot ei
n Z
FP
ki
n
esn
i -l
k
i e 7
C
U
B do
m ai
n
- con
t a
n
i n
i g prot ei
n 1
e
l u
ci
n
e-t R
N
A g
i
l ase precurso
r
X t ran
sp
ort e
r prot ei
n 3 s
i of orm
2
ch
em o
ki
n
e ( C
- C mo
t f
i) r e
ce
pt or 1
ch
em o
ki
n
e ( C
- C mo
t f
i) r e
ce
pt or 2 s
i o. . .
hypo
t h
et c
i a
l p
r o
t e
n
i
LO C
25
91
73
hu
nt n
i g
t n
i
n
it e
r a
ct n
i g p
r o
t e
n
i
B
" p
r o
t e
n
i
t yr o
si
n
e ph
osph
at ase,
n
on
- re. . .
D
E
AD
/ H (Asp-G u
l -Aa
l- A
sp
/ H
s
i ) b
ox p
ol
yp. . .
ce
l d
v
i s
io
i n cyce
l
25
A
nu
cl
e
osd
i e d
p
i h
osph
at e ki
n
ase t ype 6 (i
n. . .
" sol
u
t e carr e
ir f a
my
l
i
26
,
m em b
er 6 . . .
ari
ad
ne h
om o
o
l g 2
" u
bi
q
ui
tn
i
sp
ecf
i c
i
p
r o
t e
ase,
p
r o
t o
- o
nco. . .
ba
ssoo
n
hypo
t h
et c
i a
l p
r o
t e
n
i
MG C
8
40
7
" g
ua
ni
n
e nu
cl
e
ot d
i e b
n
i d
n
i g p
r o
t e
n
i ,
a
p
l h
a"
g2
0 prot ei
n
" a
r g
n
i n
i e-r c
i h,
mu
t a
t e
d n
i
ea
r y
l
st a
ge . . .
KI AA
08
09 p
r o
t e
n
i
hypo
t h
et c
i a
l p
r o
t e
n
i
MG C
3
97
25
" a
mn
i o
e
l vul
n
i at e,
d
el
t a-,
synt ha
se 1
"
" tr o
po
ni
n C
,
sl
o
w
"
" n
it e
r -al
p
ha (gl
o
bu
n
i
l ) n
i hi
b
t
i o
r ,
H
1"
pu
t a
t v
i e en
do
pl
a
sm c
i
ret c
i u
u
l m m ul
ts
i p
an
" cal
cu
i m ch
an
ne
,
l
vo
t
l a
ge
- d
ep
en
de
nt ,
L. . .
ch
ol
n
i e de
hydrog
en
ase
" cal
cu
i m ch
an
ne
,
l
vo
t
l a
ge
- d
ep
en
de
nt ,
a. . .
H
T
01
7 prot ei
n
" w
n
i g
e
l ss-t ype M M T
V n
i t eg
r a
t o
i n si
te f .. .
ch
r o
m osom e 1 o
pe
n r e
ad
n
i g fr a
me 1
3p
. ..
SN
P_
A-15
19
67
2
SN
P_
A-15
08
14
0
SN
P_
A-15
19
12
1
SN
P_
A-15
14
34
8
SN
P_
A-15
18
69
5
SN
P_
A-15
14
99
9
SN
P_
A-15
18
81
4
SN
P_
A-15
16
75
2
sui
1 h
om o
o
l g
" cat en
n
i
( cad
he
r n
i- a
ssoca
i t ed p
r o
t e
n
i ), . . .
3p
. ..
3p
. ..
r e
t n
i ob
a
l st o
m a-asso
ci
a
t e
d prot ei
n R
AP
14
0
R
h
o gu
an
n
i e n
uce
l o
t d
i e exch
an
ge f act o
r 3
hypo
t h
et c
i a
l p
r o
t e
n
i
D
K
FZ
p4
34
N
1
92
8
an
kyr n
i
rep
ea
t
an
d SO C
S bo
x-co
nt ai
n
n
i .. .
sa
r col
e
m m a asso
ci
a
t e
d prot ei
n
" fa
l
i mn
i
B
,
be
t a (act n
i
b
n
i d
n
i g p
r o
t e
n
i
2. . .
r b
i on
uce
l a
se P (14
kD
)
" f am y
l
i
w
t
i h seq
ue
nce si
ma
l
ir t
i y 3,
me
. ..
f rag
e
l
i
hi
st d
in
i e tr a
i d ge
ne
na
so
ph
aryn
ge
al ca
r cn
i o
m a-r e
a
l t ed p
r o
t e
n
i
SN
P_
A-15
09
38
6
SN
P_
A-15
16
69
5
SN
P_
A-15
16
77
9
SN
P_
A-15
15
23
7
SN
P_
A-15
08
19
4
SN
P_
A-15
08
13
6
SN
P_
A-15
13
83
3
SN
P_
A-15
17
29
1
SN
P_
A-15
12
98
7
SN
P_
A-15
16
37
8
SN
P_
A-15
17
75
9
SN
P_
A-15
16
53
9
SN
P_
A-15
18
95
7
SN
P_
A-15
11
38
9
SN
P_
A-15
16
35
2
SN
P_
A-15
12
44
6
SN
P_
A-15
17
29
7
SN
P_
A-15
10
59
2
SN
P_
A-15
08
66
7
SN
P_
A-15
14
81
8
SN
P_
A-15
10
90
1
SN
P_
A-15
15
47
8
SN
P_
A-15
19
35
0
SN
P_
A-15
14
37
4
SN
P_
A-15
19
17
2
SN
P_
A-15
08
16
7
SN
P_
A-15
08
79
8
SN
P_
A-15
10
55
9
SN
P_
A-15
08
60
5
SN
P_
A-15
11
15
2
SN
P_
A-15
11
27
4
SN
P_
A-15
19
20
2
SN
P_
A-15
07
86
9
3p
. ..
SN
P_
A-15
11
90
7
" p
r o
t e
n
i
t yr o
si
n
e ph
osph
at ase,
recep
t .. .
SN
P_
A-15
14
16
3
H
T
02
1
SN
P_
A-15
16
95
6
SN
P_
A-15
17
91
5
SN
P_
A-15
12
92
7
SN
P_
A-15
15
02
6
syna
pt op
ori
n
hypo
t h
et c
i a
l p
r o
t e
n
i
BC
01
52
10
SN
P_
A-15
15
69
2
a di
sn
i t eg
r n
i
a
nd m e
t a
o
l p
r o
t e
n
i a
se w
t
i h
SN
P_
A-15
19
24
3
SN
P_
A-15
16
91
8
SN
P_
A-15
19
04
4
SN
P_
A-15
18
75
4
BA
I 1
- a
ssoca
i t ed p
r o
t e
n
i
1
hypo
t h
et c
i a
l p
r o
t e
n
i
LO C
11
52
86
e
l u
ci
n
e-r c
ih r e
pe
at s an
d m
i
m un
og
o
l b
ul
n
i- k
i
le
3p
. ..
T-ce
l a
ct v
i a
t o
i n ke
c
l h rep
ea
t
prot ei
n
SN
P_
A-15
09
03
5
SN
P_
A-15
18
85
8
SN
P_
A-15
11
81
4
SN
P_
A-15
17
81
9
SN
P_
A-15
07
98
8
SN
P_
A-15
13
46
9
SN
P_
A-15
08
79
2
TA
TA e
e
l me
nt
mo
du
a
l t ory
f a
ct or
1
mc
i rop
ht ha
m
l
a
i -asso
ci
a
t e
d t ran
scr p
it o
i n. . .
f o
r khe
ad b
ox
SN
P_
A-15
15
57
8
SN
P_
A-15
12
04
7
SN
P_
A-15
13
80
7
SN
P_
A-15
11
25
9
SN
P_
A-15
11
54
4
P
1
hypo
t h
et c
i a
l p
r o
t e
n
i
MG C
3
98
20
3p
13
R
IN
G1 a
nd Y
Y1 b
n
i d
n
i g p
r o
t e
n
i
hypo
t h
et c
i a
l p
r o
t e
n
i
FL
J1
05
39
hypo
t h
et c
i a
l p
r o
t e
n
i
LO C
15
19
87
SN
P_
A-15
10
45
0
SN
P_
A-15
08
67
8
SN
P_
A-15
09
89
1
SN
P_
A-15
19
54
6
SN
P_
A-15
15
79
2
SN
P_
A-15
07
45
0
3p
. ..
r o
un
da
bo
ut
1 s
i of orm
b
SN
P_
A-15
07
39
8
SN
P_
A-15
19
68
2
SN
P_
A-15
18
42
6
SN
P_
A-15
17
01
6
SN
P_
A-15
18
29
5
SN
P_
A-15
15
59
2
3p
. ..
" g
u
l can (1, 4-al
p
ha
- ),
bran
ch
n
i g e
nzym . . .
SN
P_
A-15
08
72
4
SN
P_
A-15
17
94
7
SN
P_
A-15
13
28
3
SN
P_
A-15
10
83
7
ne
ct n
i -l
k
i e p
r o
t e
n
i
3
3p
. ..
3p
. ..
SN
P_
A-15
18
37
3
SN
P_
A-15
12
53
4
SN
P_
A-15
19
70
6
SN
P_
A-15
12
67
8
SN
P_
A-15
15
56
8
SN
P_
A-15
14
21
2
co
o
l n carci
n
om a rel
a
t e
d prot ei
n
D
K
FZ
P5
64
O 12
3 prot ei
n
5-hydroxyt r ypt am n
i e ( serot on
n
i )
hypo
t h
et c
i a
l p
r o
t e
n
i
FL
J1
09
97
rece. . .
SN
P_
A-15
13
81
8
SN
P_
A-15
18
79
1
Ep
hA
3
3p
. ..
3q
. ..
prot ei
n S (al
p
ha
)
SN
P_
A-15
15
38
1
3q
. ..
SN
P_
A-15
10
62
4
SN
P_
A-15
13
39
7
SN
P_
A-15
12
15
3
SN
P_
A-15
08
09
2
SN
P_
A-15
18
51
7
SN
P_
A-15
14
67
6
hypo
t h
et c
i a
l p
r o
t e
n
i
D
K
FZ
p4
34
C
1
41
8
hypo
t h
et c
i a
l p
r o
t e
n
i
D
K
FZ
p4
34
L1
12
3 si
m.
l
i. .
ch
r o
m osom e 3 o
pe
n r e
ad
n
i g fr a
me 4
" a
p
l h
a2
, 3
- sa
i y
lt
l ran
sf erase VI "
3q
. ..
3q
. ..
SN
P_
A-15
14
76
1
SN
P_
A-15
12
03
2
SN
P_
A-15
19
36
3
SN
P_
A-15
19
59
2
sm o
ot h m uscl
e cel
l expresse
d an
d m a. . .
hypo
t h
et c
i a
l p
r o
t e
n
i
FL
J1
10
46
N
t
i
p
r o
t e
n
i
2
G
p
r o
t e
n
i -co
up
e
l d recep
t o
r 12
8
n
i t erph
ot orecep
t o
r m at r x
i
p
r o
t e
og
y
l can 2
se
nt r n
i/ S
U
M O -sp
ecf
i c
i
p
r o
t e
ase 7
hypo
t h
et c
i a
l p
r o
t e
n
i
FL
J2
04
32
3q
. ..
SN
P_
A-15
10
11
1
SN
P_
A-15
07
44
9
SN
P_
A-15
15
88
1
SN
P_
A-15
16
49
4
hypo
t h
et c
i a
l p
r o
t e
n
i
LO C
13
13
68
SN
P_
A-15
15
97
9
SN
P_
A-15
17
05
5
SN
P_
A-15
08
04
8
SN
P_
A-15
10
91
4
3q
. ..
act v
i at ed e
l ukocyt e ce
l a
dh
eso
i n mo
e
l cul
e
C
a
s-Br- M ( m u
r n
i e) e
co
t rop
c
i
r e
t rovr
i a
l
SN
P_
A-15
10
68
7
t e
st es
SN
P_
A-15
16
11
3
SN
P_
A-15
11
51
7
SN
P_
A-15
16
28
6
SN
P_
A-15
10
75
8
SN
P_
A-15
19
39
1
SN
P_
A-15
18
53
9
3q
. ..
d
evel
o
pm e
nt - rel
a
t e
d N
Y
D
-SP
17
" C
D
4
7 an
t g
i en (R
h
- rel
a
t e
d an
t g
i en
, "
KI AA
15
24 p
r o
t e
n
i
co
o
l n a
nd sm al
ln
i t est n
i e-sp
ecf
i c
i
cyst e
n
i .. .
hypo
t h
et c
i a
l p
r o
t e
n
i
BC
01
80
70
3q
. ..
SN
P_
A-15
10
95
3
SN
P_
A-15
08
06
5
ne
ct n
i
3
3q
. ..
3q
. ..
" T cel
l act v
i at o
i n
,
n
i cr e
ased a
lt e e
xp
r e
s. . .
LL
5 be
t a
O X-2 m em b
r a
ne g
y
l cop
r o
t e
n
i
precurso
r
Ap
g3
p
ce
l surf a
ce g
y
l cop
r o
t e
n
i
r e
ce
pt or C
D
2
0. . .
brot he
r of
C
D
O
hypo
t h
et c
i a
l p
r o
t e
n
i
FL
J2
01
74
hypo
t h
et c
i a
l p
r o
t e
n
i
D
K
FZ
p4
34
C
0
32
8
do
pa
mn
i e recep
t o
r D
3 s
i of orm
a
grow
t h a
ssoca
i t ed p
r o
t e
n
i
43
m
i
l
bi
c syst e
m- a
ssoca
i t ed m e
m bran
e p. . .
3q
. ..
3q
. ..
3q
. ..
3q
. ..
3q
. ..
brai
n a
nd t est s
i - spe
ci
fc
i
m
i
m un
og
o
l b
n
i
hypo
t h
et c
i a
l p
r o
t e
n
i
FL
J3
28
59
hypo
t h
et c
i a
l p
r o
t e
n
i
FL
J1
09
02
ph
osph
at d
i ys
l e
r n
i e-sp
ecf
i c
i
p
ho
sp
ho
p
i
l a
se
G AB
AB
- rel
a
t e
d G- p
r o
t e
n
i
co
up
e
l d rece. . .
f o
s
i
l t at n
i -l
k
i e 1 p
r e
cu
r sor
N
A
D
H d
eh
yd
r o
ge
na
se (ub
q
i u
n
i o
ne
) 1 be
t a
" p
ol
ym erase ( D
N
A d
r
i e
ct ed
) ,
t he
t a
"
m uscl
e d
s
i e
ase-r e
a
l t ed p
r o
t e
n
i
so
u
l t e ca
r ri
er f am y
l
i
1
5 ( H
+/ pe
pt d
i e
ca
c
l u
i m - sen
si
n
g r e
ce
pt or (hypo
ca
c
l u
ir c
i
B ag
gressi
ve y
l mp
ho
m a ge
ne
f o
r prot ei
n d
s
i u
f
l d
ie s
i o
m erase-r e
a
l t ed
SE
C
2
2 ve
si
ce
l
t raf f c
i ki
n
g prot ei
n
- k
i
le 2
m yo
si
n g
i
l ht
cha
n
i
ki
n
ase s
i o
f o
r m 1
hypo
t h
et c
i a
l p
r o
t e
n
i
FL
J1
28
92
se
r n
i e/ t h
r e
on
n
i e kn
i a
se w
t
i h D
bl
- a
nd p
e
l .. .
" n
it e
gri
n,
b
et a 5"
so
u
l t e ca
r ri
er f am y
l
i
1
2 ( p
ot assi
u
m / chl
.. .
so
r tn
i g n
exn
i
4
hypo
t h
et c
i a
l p
r o
t e
n
i
FL
J2
04
73
f o
r m yt
l e
t rah
yd
r o
f o
a
l t e de
hydrog
en
ase. . .
hypo
t h
et c
i a
l p
r o
t e
n
i
FL
J2
01
23
hypo
t h
et c
i a
l p
r o
t e
n
i
MG C
1
30
16
hypo
t h
et c
i a
l p
r o
t e
n
i
D
K
FZ
p5
64
A1
76
se
ve
n t ran
sm e
m bran
e do
m ai
n o
r p
ha
n. . .
an
kyr n
i
rep
ea
t
an
d BT
B ( P
O Z) d
om a
n
i .. .
Se
c6
1 al
p
ha f orm
1
hypo
t h
et c
i a
l p
r o
t e
n
i
MG C
3
38
84
r b
i op
ho
r n
i
I
hypo
t h
et c
i a
l p
r o
t e
n
i
FL
J1
20
57
" coa
t o
m er p
r o
t e
n
i
co
m pl
e
x,
sub
un
t
i
g. . .
3q
. ..
t h
yrot r o
pi
n
- rel
e
asn
i g h
orm on
e
hypo
t h
et c
i a
l p
r o
t e
n
i
FL
J3
58
80
" p
ho
sp
ho
n
i o
si
td
i e
- 3
- kn
i a
se
,
r e
gu
a
l t ory
" A
TP
ase,
C
a+
+-se
qu
est e
r n
i g"
hypo
t h
et c
i a
l p
r o
t e
n
i
FL
J3
12
65
co
pi
n
e I V
3q
. ..
ph
akn
i n
i
hypo
t h
et c
i a
l p
r o
t e
n
i
H
4
1
PR
O 20
86 p
r o
t e
n
i
R
Y
K r e
ce
pt or- k
i
l e t yr o
si
n
e ki
n
ase precu. . .
hypo
t h
et c
i a
l p
r o
t e
n
i
FL
J1
33
86
ep
hri
n r e
ce
pt or E
ph
B1 p
r e
cu
r sor
SN
P_
A-15
08
54
1
SN
P_
A-15
09
40
7
SN
P_
A-15
09
69
3
SN
P_
A-15
14
34
5
SN
P_
A-15
17
03
1
SN
P_
A-15
12
12
4
SN
P_
A-15
14
60
2
SN
P_
A-15
11
41
3
SN
P_
A-15
09
36
7
SN
P_
A-15
08
47
5
SN
P_
A-15
12
48
7
SN
P_
A-15
17
52
2
SN
P_
A-15
08
28
8
SN
P_
A-15
14
64
7
SN
P_
A-15
16
09
1
SN
P_
A-15
17
26
6
SN
P_
A-15
17
99
4
SN
P_
A-15
11
31
0
SN
P_
A-15
16
26
1
SN
P_
A-15
11
11
5
SN
P_
A-15
14
13
5
SN
P_
A-15
11
65
3
SN
P_
A-15
16
81
7
SN
P_
A-15
16
52
2
SN
P_
A-15
15
18
5
SN
P_
A-15
17
01
1
SN
P_
A-15
08
26
9
SN
P_
A-15
14
14
0
SN
P_
A-15
09
48
0
SN
P_
A-15
15
11
5
SN
P_
A-15
15
35
1
SN
P_
A-15
11
67
8
s. . .
SN
P_
A-15
09
50
2
prost a
t c
i
a
ci
d p
ho
sp
ha
t a
se p
r e
cu
r sor
hypo
t h
et c
i a
l p
r o
t e
n
i
FL
J1
25
92
" p
r o
t e
n
i
ph
osph
at ase 2 ( f orm erl
y
hypo
t h
et c
i a
l p
r o
t e
n
i
FL
J1
05
46
st r o
m al an
t g
i en 1
hypo
t h
et c
i a
l p
r o
t e
n
i
MG C
3
29
5
hypo
t h
et c
i a
l p
r o
t e
n
i
MG C
3
49
23
SN
P_
A-15
10
35
9
SN
P_
A-15
19
43
7
SN
P_
A-15
16
46
2
SN
P_
A-15
09
06
7
SN
P_
A-15
08
74
5
SN
P_
A-15
17
01
3
SN
P_
A-15
11
98
6
SN
P_
A-15
12
58
5
SN
P_
A-15
12
02
8
SN
P_
A-15
11
08
8
SN
P_
A-15
14
79
1
SN
P_
A-15
10
20
6
SN
P_
A-15
11
85
3
SN
P_
A-15
11
35
3
SN
P_
A-15
10
57
0
SN
P_
A-15
18
87
6
SN
P_
A-15
18
14
4
2A
) .. .
SN
P_
A-15
12
99
8
3q
. ..
SR
Y ( sex d
et erm n
i n
ig r e
gi
o
n Y)- b
ox
cl
a
ud
n
i
18
m uscl
e R
AS o
ncog
en
e ho
m ol
o
g
Fa
s ap
op
t o
t c
i
n
i hi
b
t
i o
r y mo
e
l cul
e
f o
r khe
ad b
ox L
2
mt
i o
ch
on
dri
al r b
i osom a
l p
r o
t e
n
i
S2
2
hypo
t h
et c
i a
l p
r o
t e
n
i
FL
J1
18
27
ca
s
l ynt en
n
i -2
3q
23
1
4
t ri
pa
r tt
i e mo
t f
i - con
t a
n
i n
i g 42
hypo
t h
et c
i a
l p
r o
t e
n
i
FL
J1
06
18
hypo
t h
et c
i a
l p
r o
t e
n
i
FL
J2
37
51
R
A
S p2
1 prot ei
n a
ct v
i a
t o
r 2
" A
TP
ase,
N
a+
/ K
+ t ran
sp
ort n
i g,
b
et a 3. . .
hypo
t h
et c
i a
l p
r o
t e
n
i
MG C
4
05
79
pl
a
st n
i
1
procol
a
l ge
n C
-en
do
pe
pt d
i a
se e
nh
an
ce
r 2
ca
r b
oh
yd
r a
t e (N
-acet yl
g
u
l cosam n
i e-6-O )
hypo
t h
et c
i a
l p
r o
t e
n
i
MG C
3
33
65
SN
P_
A-15
15
78
6
SN
P_
A-15
18
42
8
SN
P_
A-15
13
85
1
SN
P_
A-15
09
74
6
SN
P_
A-15
18
56
2
SN
P_
A-15
16
85
1
SN
P_
A-15
17
01
7
SN
P_
A-15
16
01
4
SN
P_
A-15
16
41
2
SN
P_
A-15
15
10
0
SN
P_
A-15
07
69
2
SN
P_
A-15
14
50
7
SN
P_
A-15
13
80
5
SN
P_
A-15
12
64
6
SN
P_
A-15
18
84
6
SN
P_
A-15
09
74
1
SN
P_
A-15
13
01
2
3q
24
hypo
t h
et c
i a
l p
r o
t e
n
i
PR
O 25
33
ph
osph
ol
p
id
i
scr a
m bl
a
se 2
zi
n
c
f n
i ge
r
prot ei
n o
f
SN
P_
A-15
18
36
4
SN
P_
A-15
12
83
7
SN
P_
A-15
12
13
1
t h
e ce
r e
be
u
l m
4
SN
P_
A-15
16
18
5
3q
. ..
" a
ng
o
i t en
si
n II
r e
ce
pt or,
t ype 1
"
gl
yco
ge
ni
n
hypo
t h
et c
i a
l p
r o
t e
n
i
BC
01
43
39
H
S
PC
04
2 prot ei
n
prof n
i
l
2 s
i o
f o
r m b
KI AA
06
69 g
en
e prod
uct
st r e
ss- a
ssoca
i t ed e
nd
op
a
l sm c
i
r e
t c
i ul
u
. ..
U
S
H
3
A prot ei
n s
i of orm
c
pl
a
t e
e
l t
a
ct v
i a
t n
ig r e
ce
pt or h
om o
o
l g
aryl
a
ce
t a
md
i e d
ea
ce
t ya
l se
m uscl
e
bl
n
i d-l
k
i e
pu
r n
i ergi
c recep
t o
r P2
Y1
" R
AP
2B
,
m em b
er o
f
R
A
S on
co
ge
ne f a. . .
SN
P_
A-15
14
38
3
SN
P_
A-15
14
14
9
SN
P_
A-15
19
58
0
SN
P_
A-15
10
59
1
SN
P_
A-15
10
37
8
SN
P_
A-15
07
89
1
SN
P_
A-15
12
37
7
SN
P_
A-15
11
68
8
SN
P_
A-15
18
56
4
SN
P_
A-15
11
22
8
SN
P_
A-15
09
53
5
SN
P_
A-15
16
82
8
SN
P_
A-15
10
95
8
3q
. ..
D
K
FZ
P4
34
D
1
46 p
r o
t e
n
i
m em b
r a
ne m e
t a
o
l -en
do
pe
pt d
i a
se
3q
. ..
hypo
t h
et c
i a
l p
r o
t e
n
i
FL
J3
11
39
" p
ot assi
u
m
vol
t ag
e-ga
t e
d ch
an
ne
,
l
sh
a. . .
si
g
na
l seq
ue
nce r e
ce
pt or g
am m a sub
un
t
i
cycl
n
i
L a
ni
a
- 6
a
" p
en
t a
xi
n
- rel
a
t e
d ge
ne
,
sh
ort
r a
pi
d
y
l
st at ure ho
m eo
bo
x
n
i d
uced . . .
2 s
i o
f o
r m
a
SN
P_
A-15
13
62
2
SN
P_
A-15
16
47
5
SN
P_
A-15
13
02
6
SN
P_
A-15
18
78
2
SN
P_
A-15
17
20
5
3q
. ..
m ye
o
l d
i
e
l ukem a
i
f act o
r
1
schw
an
no
mn
i
n
i t eract n
i g prot ei
n 1
3q
. ..
n
i t erl
eu
ki
n 1
2A p
r e
cu
r sor
SM C
4 st r u
ct ural m ai
n
t e
na
nce of
chro. . .
ka
r yop
he
r n
i
a
p
l h
a 4
pu
t a
t v
i e prot ei
n p
ho
sp
ha
t a
se t yp
e 2C
C
G I- 0
7 prot ei
n
SN
P_
A-15
16
56
7
SN
P_
A-15
09
17
5
SN
P_
A-15
10
31
5
SN
P_
A-15
15
84
4
SN
P_
A-15
19
37
8
SN
P_
A-15
07
67
9
SN
P_
A-15
12
46
4
SN
P_
A-15
17
68
8
SN
P_
A-15
14
09
6
SN
P_
A-15
19
26
4
SN
P_
A-15
09
93
1
SN
P_
A-15
11
49
3
SN
P_
A-15
09
92
6
SN
P_
A-15
12
57
5
SN
P_
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14
41
2
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14
65
7
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crase-i
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SN
P_
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12
67
6
SN
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08
62
7
SN
P_
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19
25
2
hypo
t h
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n
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FL
J2
30
49
prog
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at h 10
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i
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ie G
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grow
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18
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18
96
5
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19
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7
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97
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61
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10
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65
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09
43
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P_
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16
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13
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P_
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07
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in
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1
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P_
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07
53
1
SN
P_
A-15
08
79
5
SN
P_
A-15
17
08
2
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P_
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11
77
9
SN
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11
81
3
SN
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17
82
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68
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16
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9
hypo
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D
C
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ma
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ph
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16
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67
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6
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12
45
7
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12
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14
83
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P_
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15
96
5
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10
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9
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no
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/ 3
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r b
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k
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m at ost a
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LI M
3q
28
2
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om a
n
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f e
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m or p
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n
i
p7
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k
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m a asso
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ud
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16
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42
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18
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7
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09
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P_
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13
55
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P_
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1
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P_
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17
44
8
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P_
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18
23
5
SN
P_
A-15
12
14
0
SN
P_
A-15
19
07
8
SN
P_
A-15
14
59
1
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P_
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09
29
3
SN
P_
A-15
15
59
6
SN
P_
A-15
12
01
8
SN
P_
A-15
09
61
3
SN
P_
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09
41
3
SN
P_
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14
08
5
SN
P_
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09
24
2
SN
P_
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14
38
2
ch
r o
m osom e 3 o
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n r e
ad
n
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me 6
f b
ir o
bl
a
st
3q
29
g
r o
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th f a
ct or
1
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f o
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P_
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18
28
9
2
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pp
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pe
at
p
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uced b
y be
t a
hypo
t h
et c
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n
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BC
00
77
72
hypo
t h
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J3
51
55
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t a
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b
et a 2"
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r o
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n
i
ph
osph
at ase 1,
reg
ul
a
t o
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n. . .
act v
i at ed p
21
cd
c4
2H
s ki
n
ase
hypo
t h
et c
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t e
n
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MG C
3
33
45
hypo
t h
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n
i
FL
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57
94
p2
1-act v
i at ed kn
i a
se 2
SN
P_
A-15
11
52
2
SN
P_
A-15
12
56
9
SN
P_
A-15
09
61
0
SN
P_
A-15
18
22
4
SN
P_
A-15
12
63
6
SN
P_
A-15
17
10
8
SN
P_
A-15
10
62
3
SN
P_
A-15
10
94
4
SN
P_
A-15
10
46
6
3-hydroxyb
ut yrat e de
hydrog
en
ase pre. . .
hypo
t h
et c
i a
l p
r o
t e
n
i
D
K
FZ
p7
61
B1
51
4
SN
P_
A-15
12
00
1
12
5026.10_1
5026.10_2
5026.10_3
5026.10_4
5026.10_5
5026.10_6
5026.10_7
1
1
2
2
2
1
2
Affected
Linkage analysis using SNP array: peak LOD score region
13
Non-parametric linkage analysis using allele sharing
Peak region 3.8Mb (17
SNPs and 21 genes),
genome-wide
permutation p-value <
0.001
10K SNP array data
from Puffenberger et
al. 2004 PNAS
Copy number analysis of SNP array data
•
•
•
•
dChip (Zhao et al. 2004)
Affy CNAT (2004)
Japan’s CNAG (2005)
PLASQ (LaFramboise et al. 2005)
• Affy CARAT (2006)
• GIM (2005)
14
Normalization: Arrays may have different brightness
Expression value computation using multiple arrays
15
Obtain signal values from SNP array
AB
AA
A?
Copy number analysis using SNP array
•Normalization and model-based signal for each array
and SNP
•For a SNP, the signal values of all normal cell lines
were averaged to obtain the mean signal of 2 copy;
observed copy number = (observed signal / mean signal
of two copy) * 2
•HMM to infer real copy number by best path
16
Raw copy numbers
HMM inferred copy numbers
17
SNP-array copy number vs. Q-PCR
Zhao et al. 2004
Copy number summary plot
As in Zhao et al. 2005 Cancer Research
18
Copy number variation in normal samples
• The assumption that normal samples have copy
2 everywhere may not hold (Iafrate et al. 2004,
Sebat et al. 2004).
• Could distinguish such copy number
polymorphism (CNP) regions of the genome by
excluding known CNP found in normal samples
from cancer samples
– Human Structural Variation Database (Sharp et al.
2005)
– WayStation database
Alternatively, use trimmed method to obtain
normal signal variations, e.g. assume 80% of
normal samples are really 2 copy for any locus
The CNVs of chromosome 22 identified in 90 normal individuals using
the 100K Xba sub-array. Rows are ordered SNPs and columns are
samples. The whiter colors corresponds to lower than 2 copies
(homozygous or hemizygous deletions). The CNVs are between the region
20.7 – 22 Mb (22q11.22 -- q11.23). The CNV in this region have also been
reported by (Iafrate et al. 2004; Sharp et al. 2005). Sample F4 and F6 are
from the same family.
19
dChip software for microarray analysis
User Dialog for automating
20
Displaying a viewpoint
Analysis report
21
Using dChip to analyze SNP arrays for LOH and copy
number analysis
dChip homepage: www.dchip.org
Download dChip
http://biosun1.harvard.edu/~cli/dchip.exe (download to a directory, e.g. "c:\dchip")
Demonstration data package for 10k SNP array:
Download http://www.dchip.org/lung_10k_demo_data.zip
(90 MB), unzip files into a directory and click dchip.exe to run several automated menu
functions.
Steps to analyze new SNP data
1. Use dChip to open data Click to run dchip.exe, select menu "Analysis/Open group"
2. Normalize and compute signal
Select menu "Analysis/Normalize & Model".
3. View SNPs along chromosome
Select menu "Analysis/Chromosome"
4. Explore more functions
See dChip manual, "SNP array analysis" sections:
http://www.dchip.org/manual.htm
Adjusting chromosome views:
http://www.dchip.org/chromosome.htm#adjust
Copy number summary plot:
http://www.dchip.org/copy.htm#summary_plot
Sample clustering: http://www.dchip.org/snp_cluster.htm
Export SNP data: http://www.dchip.org/snp.htm#export_data
Combine subarrays: http://www.dchip.org/combine%20chip.htm#sub_chip
Gene expression analysis demo data
http://biosun1.harvard.edu/~cli/dchip_demo.rar