supplementary information - chapter 5 d.pdf · supplementary information - chapter 5 201. d...
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DSupplementary Information - Chapter 5
201
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Appendix D
d.1 description of network properties
By focusing on the topological properties, our knowledge of the behavior of theproteins in a protein-protein interaction network can be increased. NetworkAnal-yser in Cytoscape is able to compute a range of topological features over a givenset of protein-protein interactions (Assenov et al., 2008; Doncheva et al., 2012).Some of these properties provide information about the direct neighborhood of aprotein (local property), while others provide information about the role of theproteins in the global network (global property). These features -which are usedfor analysis in this study- are briefly described below:
• The degree of a protein indicates the number of interactions the protein haswith other proteins in the network. Proteins with a high degree are alsoknown as hub genes and are suggested to have an important role in theregulation of the system (local property) (Diestel, 2005).
• The clustering coe�cient reflects the degree of connectivity between neigh-boring proteins. It is a ratio of the number of observed interactions betweenall neighbors of a protein divided by the maximum number of possible inter-actions between the neighbors of the protein. A high clustering coe�cientindicates a tight connected local network (local property) (Watts & Strogatz,1998; Barabasi & Oltvai, 2004).
• Betweenness centrality is a measure for the amount of control that a pro-tein exerts over all other proteins in the network and is calculated on basisof the number of shortest paths going through the given protein. A highbetweenness indicates a more important role of the protein in the networkorganization (global property) (Yoon et al., 2006).
• Eccentricity is the maximum length of the shortest path between a proteinand any other protein in the network. It is an indicator of the location ofthe node in the network. The more a protein is in the periphery, the higherthe eccentricity (global property).
• Closeness centrality is an indicator for the speed of spreading informationfrom a given protein to every other protein in the network. A protein witha high closeness is on average close to other proteins in the network (globalproperty) (Newman, 2005).
203
Appendix D
• Radiality of a protein is a measure that reflects the centrality of the proteinand is a measure of the number of shortest paths that goes through a proteincompared to all other proteins in the network. A radiality higher than theaverage radiality of the network indicates that the protein is in proximityto other proteins, where proteins with a lower radiality indicates tend to belocated in the periphery (global property) (Brandes, 2001).
• Stress of a protein indicates the number of shortest paths of all proteins inthe network that pass the protein. The higher this number, the bigger therole of the protein in given network (global property) (Brandes, 2001).
• The topological coe�cient is a relative measure to indicate the extent towhich a protein shares interacting partners with other proteins (global prop-erty) (Stelzl et al., 2005).
Distribution of Gene Size (corrected data)
Gene Size (corrected data)
Freq
uenc
y
0 200000 400000 600000 800000 1000000 1400000
050
0010
000
1500
0
Distribution of Exon Size
Exon Size
Freq
uenc
y
0 20000 40000 60000 80000 100000 120000
050
0010
000
1500
0
Figure D.1 Distribution plots [continues on next page]
204
DDDDDDDDDD
Appendix D
Distribution of # Unique Exons (corrected data)
# Unique Exons (corrected data)
Freq
uenc
y
0 5 10 15 20
050
010
0015
00
Distribution of # isoforms
# isoforms
Freq
uenc
y
0 10 20 30 40 50 60
020
0040
0060
0080
00Distribution of # expressed tissues
# expressed tissues
Freq
uenc
y
0 10 20 30 40
050
010
0015
00
Distribution of Sequenced Exon Size
Sequenced Exon Size
Freq
uenc
y
0 5000 10000 15000 20000 25000
010
0020
0030
0040
00
Distribution of Common Variants (corrected data)
Common Variants (corrected data)
Freq
uenc
y
0 10 20 30 40 50
050
010
0015
0020
0025
0030
00
Distribution of Rare Variants (corrected data)
Rare Variants (corrected data)
Freq
uenc
y
0 20 40 60 80 100
050
010
0015
00
Figure D.1 Distribution plots [continues on next page]
205
Appendix D
Distribution of Non−Synonymous Variants (corrected data)
Non−Synonymous Variants (corrected data)
Freq
uenc
y
0 5 10 15
020
0040
0060
0080
0010
000
1200
0
Distribution of Missense Variants (corrected data)
Missense Variants (corrected data)Fr
eque
ncy
0 20 40 60 80 100
050
010
0015
00
Distribution of Splice Variants (corrected data)
Splice Variants (corrected data)
Freq
uenc
y
0 10 20 30 40 50
050
0010
000
1500
0
Distribution of Degree
Degree
Frequency
0 500 1000 1500
02000
4000
6000
8000
10000
12000
Distribution of Clustering Coefficient
Clustering Coefficient
Freq
uenc
y
0.0 0.2 0.4 0.6 0.8 1.0
010
0020
0030
0040
0050
00
Distribution of Betweenness Centrality
Betweenness Centrality
Freq
uenc
y
0.0 0.2 0.4 0.6 0.8 1.0
020
0040
0060
0080
0010
000
1200
014
000
Figure D.1 Distribution plots [continues on next page]
206
DDDDDDDDDD
Appendix D
Distribution of Eccentricity
Eccentricity
Frequency
2 4 6 8 10
02000
4000
6000
8000
Distribution of Closeness Centrality
Closeness Centrality
Freq
uenc
y
0.2 0.4 0.6 0.8 1.0
050
010
0015
0020
0025
0030
00Distribution of Radiality
Radiality
Frequency
0.5 0.6 0.7 0.8 0.9 1.0
0500
1000
1500
Distribution of Stress
Stress
Frequency
0e+00 1e+08 2e+08 3e+08 4e+08 5e+08
02000
4000
6000
8000
10000
12000
Distribution of Topological Coefficient
Topological Coefficient
Freq
uenc
y
0.0 0.2 0.4 0.6 0.8 1.0
050
010
0015
0020
0025
00
Figure D.1 Distribution plots
207
Appendix D
020000
40000
60000
Gene Size (corrected data)
Essential Mono Complex Non−Associated
02000
4000
6000
8000
10000
Exon Size
Essential Mono Complex Non−Associated
02
46
810
# Unique Exons (corrected data)
Essential Mono Complex Non−Associated
24
68
1012
# Isoforms
Essential Mono Complex Non−Associated
010
2030
40
# Expressed Tissues
Essential Mono Complex Non−Associated
01000
2000
3000
4000
Sequenced Exon Size
Essential Mono Complex Non−Associated
Figure D.2 Boxplots [continues on next page]
208
DDDDDDDDDD
Appendix D
02
46
810
Common Variants (corrected data)
Essential Mono Complex Non−Associated
010
2030
40
Rare Variants (corrected data)
Essential Mono Complex Non−Associated
0.0
0.2
0.4
0.6
0.8
1.0
1.2
Non−Synonymous Variants (corrected data)
Essential Mono Complex Non−Associated
05
1015
2025
30Missense Variants (corrected data)
Essential Mono Complex Non−Associated
−1.0
−0.5
0.0
0.5
1.0
Splice Variants (corrected data)
Essential Mono Complex Non−Associated
020
4060
80
Degree
Essential Mono Complex Non−Associated
Figure D.2 Boxplots [continues on next page]
209
Appendix D
0.0
0.1
0.2
0.3
0.4
Clustering Coefficient
Essential Mono Complex Non−Associated
0e+00
1e−04
2e−04
3e−04
4e−04
Betweenness Centrality
Essential Mono Complex Non−Associated
5.0
5.5
6.0
6.5
7.0
7.5
8.0
Eccentricity
Essential Mono Complex Non−Associated
0.20
0.25
0.30
0.35
0.40
Closeness Centrality
Essential Mono Complex Non−Associated
0.70
0.75
0.80
0.85
Radiality
Essential Mono Complex Non−Associated
0500000
1000000
1500000
2000000
2500000
Stress
Essential Mono Complex Non−Associated
Figure D.2 Boxplots [continues on next page]
210
DDDDDDDDDD
Appendix D
0.0
0.1
0.2
0.3
0.4
0.5
0.6
Topological Coefficient
Essential Mono Complex Non−Associated
Figure D.2 Boxplots for each gene characteristicfor each of the gene classes (corrected data). Thewidth of the boxplots indicates the size of the geneclass. Note: an IQR of zero will result in only ahorizontal line that indicates the median for thegene class. This is the case for ’non-synonymousvariant’, ’splice variants’ and ’eccentricity’.
211
Appendix D
Tabl
eD
.1C
orre
latio
nta
ble
onth
eda
taco
llect
edon
the
19di
�ere
ntch
arac
teri
stic
s.M
oder
ate
(ant
i-)co
rrel
atio
ns(>
=0.
4-
<0.
7)ar
ein
dica
ted
inor
ange
and
stro
ngco
rrel
atio
ns(
>=
0.7)
are
indi
cate
din
gree
n.
Gen
eSi
ze1
Exo
nSi
ze0.
641
#E
xons
0.66
0.58
1
#E
xpre
ssed
Tis
sues
0.11
0.11
0.12
1
#Is
ofor
ms
0.34
0.28
0.48
0.11
1
Sequ
ence
dE
xon
Size
0.58
0.64
0.69
0.08
0.24
1
Rar
eV
aria
nts
0.43
0.48
0.57
0.01
0.17
0.86
1
Com
mon
Var
iant
s0.
260.
290.
37-0
.06
0.06
0.62
0.73
1
Mis
sens
eV
aria
nts
0.35
0.39
0.48
-0.0
10.
110.
760.
920.
761
Non
-Syn
Var
iant
s0.
030.
010.
09-0
.04
-0.0
20.
190.
310.
300.
351
Splic
eV
aria
nts
0.12
0.04
0.22
-0.0
50.
050.
160.
230.
210.
240.
191
Deg
ree
0.07
0.08
0.19
0.17
0.16
0.12
0.01
-0.0
6-0
.07
-0.1
3-0
.06
1
Clu
ster
ing
Coe
�ci
ent
0.05
0.06
0.10
0.11
0.06
0.08
0.01
-0.0
3-0
.02
-0.0
6-0
.03
0.52
1
Bet
wee
nnes
s0.
060.
070.
170.
130.
150.
100.
00-0
.06
-0.0
7-0
.13
-0.0
50.
910.
351
Ecc
entr
icit
y-0
.06
-0.0
7-0
.15
-0.1
4-0
.11
-0.1
1-0
.03
0.03
0.03
0.09
0.06
-0.6
5-0
.29
-0.5
91
Clo
sene
ss0.
100.
120.
190.
190.
140.
140.
02-0
.05
-0.0
5-0
.13
-0.0
70.
800.
460.
75-0
.72
1
Rad
ialit
y0.
100.
120.
190.
200.
140.
140.
02-0
.05
-0.0
5-0
.13
-0.0
60.
810.
460.
75-0
.71
1.00
1
Stre
ss0.
060.
070.
170.
150.
150.
110.
00-0
.06
-0.0
7-0
.13
-0.0
60.
920.
380.
99-0
.61
0.79
0.79
1
Top
olog
ical
Coe
�ci
ent
0.00
-0.0
1-0
.03
-0.0
5-0
.03
-0.0
30.
010.
020.
030.
030.
04-0
.10
0.21
-0.0
60.
19-0
.18
-0.1
8-0
.06
1
GeneSize
ExonSize
#Exons
#ExpressedTissues
#Isoforms
SequencedExonSize
RareVariants
CommonVariants
MissenseVariants
Non-SynVariants
SpliceVariants
Degree
ClusteringCoe�cient
Betweenness
Eccentricity
Closeness
Radiality
Stress
TopologicalCoe�cient212
DDDDDDDDDD
Appendix D
Tabl
eD
.2D
escr
iptiv
est
atis
tics
per
gene
clas
s(u
ncor
rect
edda
ta).
Ess
enti
alG
enes
Mon
ogen
icG
enes
nge
nes
mea
nsd
med
ian
IQR
nge
nes
mea
nsd
med
ian
IQR
gene
size
3473
1597
234
731
8498
1327
832
8216
737
3167
690
2813
430
exon
size
3473
4293
3484
3500
3122
3282
4182
3569
3368
3151
#un
ique
exon
s34
733.
62.
13.
33.
232
824.
02.
23.
73.
2#
isof
orm
s33
394.
74.
04.
04.
031
594.
64.
03.
04.
0#
expr
esse
dti
ssue
s29
0331
.212
.936
.020
.026
9929
.913
.735
.021
.0
sequ
ence
dex
onsi
ze30
7617
5617
2912
9113
5329
4218
2717
9013
5613
65#
com
mon
vari
ants
3076
2.6
2.2
2.2
2.5
2942
3.1
2.8
2.6
2.8
#ra
reva
rian
ts30
7618
.17.
617
.49.
429
4219
.78.
118
.89.
9#
non
syno
nym
ous
vari
ants
3076
0.2
0.5
0.0
0.0
2942
0.3
0.6
0.0
0.3
#m
isse
nse
vari
ants
3076
10.8
6.3
10.2
8.1
2942
12.5
6.8
12.0
8.7
#sp
lice
vari
ants
3076
0.1
0.5
0.0
0.0
2942
0.1
0.5
0.0
0.0
degr
ee31
6833
.874
.013
3028
1324
.755
.99
21cl
uste
ring
coe�
cien
t31
680.
126
0.16
70.
083
0.15
628
130.
128
0.18
60.
071
0.16
7be
twee
nnes
sce
ntra
lity
3168
0.00
10.
018
0.00
00.
000
2813
0.00
00.
001
0.00
00.
000
ecce
ntri
city
3168
6.6
0.7
71.
0028
136.
70.
77
1.00
clos
enes
sce
ntra
lity
3168
0.31
70.
053
0.31
80.
049
2813
0.31
30.
067
0.31
00.
048
radi
ality
3168
0.77
80.
044
0.78
60.
050
2813
0.77
20.
046
0.77
80.
051
stre
ss31
6822
9903
412
9758
2619
0093
1038
057
2813
1545
132
8475
956
8638
869
6556
topo
logi
calc
oe�
cien
t31
680.
137
0.14
50.
080
0.14
728
130.
156
0.15
50.
101
0.18
2
213
Appendix D
[Tab
leD
.2co
ntin
ued]
Des
crip
tive
stat
istic
spe
rge
necl
ass
(unc
orre
cted
data
.
Com
plex
Trai
tG
enes
Non
-Ass
ocia
ted
Gen
esn
gene
sm
ean
sdm
edia
nIQ
Rn
gene
sm
ean
sdm
edia
nIQ
R
gene
size
3872
3147
953
771
1574
426
097
1101
611
429
1988
964
6910
297
exon
size
3872
4714
3560
3988
3558
1101
630
5622
3925
0824
76#
uniq
ueex
ons
3872
3.8
2.1
3.6
3.0
1101
63.
62.
33.
23
#is
ofor
ms
3748
4.9
3.9
4.0
4.0
1084
53.
63.
23.
04
#ex
pres
sed
tiss
ues
3267
30.8
12.8
36.0
19.0
8932
30.7
12.6
35.0
19
sequ
ence
dex
onsi
ze32
4719
6918
0214
8014
8887
4212
1110
3795
796
2#
com
mon
vari
ants
3247
3.3
2.9
2.7
2.7
8742
3.6
3.5
2.7
3.7
#ra
reva
rian
ts32
4719
.87.
718
.99.
087
4220
.89.
619
.710
.9#
non
syno
nym
ous
vari
ants
3247
0.3
0.6
0.0
0.3
8742
0.4
0.9
0.0
0.5
#m
isse
nse
vari
ants
3247
12.8
6.7
12.3
8.3
8742
14.0
8.4
13.1
10.1
#sp
lice
vari
ants
3247
0.1
0.4
0.0
0.0
8742
0.2
1.0
0.0
0.0
degr
ee30
6819
.445
.56
1671
9515
.639
.85
13cl
uste
ring
coe�
cien
t30
680.
124
0.19
00.
061
0.16
771
950.
134
0.21
00.
048
0.18
3be
twee
nnes
sce
ntra
lity
3068
0.00
10.
018
0.00
00.
000
7195
0.00
10.
020
0.00
00.
000
ecce
ntri
city
3068
6.8
0.7
71
7195
6.8
0.7
70
clos
enes
sce
ntra
lity
3068
0.30
70.
058
0.30
70.
047
7195
0.30
50.
060
0.30
40.
047
radi
ality
3068
0.76
70.
045
0.77
40.
051
7195
0.76
40.
046
0.77
10.
052
stre
ss30
6810
3247
362
4351
344
725
3858
9971
9572
0008
5320
972
2052
021
4150
topo
logi
calc
oe�
cien
t30
680.
163
0.16
40.
104
0.21
571
950.
173
0.17
40.
113
0.23
4
214
DDDDDDDDDD
Appendix D
Tabl
eD
.3W
ilcox
onRa
nkSu
mte
stre
sults
for
pair
-wis
eco
mpa
riso
nbe
twee
nth
ege
necl
asse
s(–
=8.
77e-
05).
Apo
sitiv
eZ-
scor
ein
dica
tes
that
gene
clas
sA
has
ahi
gher
rank
than
gene
clas
sB
and
ane
gativ
eZ-
scor
er
indi
cate
sth
atsa
mpl
eA
has
asm
alle
rra
nkth
ange
necl
ass
B.
Ess
enti
alvs
.M
onog
enic
Ess
enti
alvs
.C
ompl
exE
ssen
tial
vs.
Non
-Ass
ocia
tate
dZ-
scor
eP
-val
uer
Z-sc
ore
P-v
alue
rZ-
scor
eP
-val
uer
gene
size
*-2
.98
2.90
E-0
3-0
.047
-28.
10<
2.2E
-16
-0.3
8513
.79
<2.
2E-1
60.
115
exon
size
3.78
1.58
E-0
40.
059
-8.7
1<
2.2E
-16
-0.1
1926
.00
<2.
2E-1
60.
216
#un
ique
exon
s*-8
.47
<2.
2E-1
6-0
.133
-4.7
22.
34E
-06
-0.0
653.
494.
81E
-04
0.02
9#
isof
orm
s1.
152.
48E
-01
0.01
8-4
.58
4.61
E-0
6-0
.064
15.5
3<
2.2E
-16
0.13
0#
expr
esse
dti
ssue
s4.
143.
42E
-05
0.07
22.
292.
18E
-02
0.03
43.
416.
39E
-04
0.03
1
sequ
ence
dex
onsi
ze-2
.45
1.42
E-0
2-0
.041
-9.2
3<
2.2E
-16
-0.1
3719
.49
<2.
2E-1
60.
179
#co
mm
onva
rian
ts**
-9.4
0<
2.2E
-16
-0.1
57-1
2.53
<2.
2E-1
6-0
.186
-12.
29<
2.2E
-16
-0.1
13#
rare
vari
ants
**-1
0.83
<2.
2E-1
6-0
.181
-10.
51<
2.2E
-16
-0.1
56-1
4.01
<2.
2E-1
6-0
.129
#no
nsy
nony
mou
sva
rian
ts**
-9.4
2<
2.2E
-16
-0.1
57-9
.14
<2.
2E-1
6-0
.135
-12.
06<
2.2E
-16
-0.1
11#
mis
sens
eva
rian
ts**
-13.
65<
2.2E
-16
-0.2
28-1
4.98
<2.
2E-1
6-0
.222
-19.
90<
2.2E
-16
-0.1
83#
splic
eva
rian
ts**
-5.5
03.
86E
-08
-0.0
92-5
.71
1.12
E-0
8-0
.085
-1.3
31.
83E
-01
-0.0
12
degr
ee11
.74
<2.
2E-1
60.
198
18.9
7<
2.2E
-16
0.28
726
.06
<2.
2E-1
60.
256
clus
teri
ngco
e�ci
ent
3.91
9.19
E-0
50.
066
7.44
1.01
E-1
30.
113
8.65
<2.
2E-1
60.
085
betw
eenn
ess
cent
ralit
y10
.77
<2.
2E-1
60.
182
18.3
1<
2.2E
-16
0.27
727
.13
<2.
2E-1
60.
267
ecce
ntri
city
-8.9
4<
2.2E
-16
-0.1
51-1
3.26
<2.
2E-1
6-0
.201
-18.
22<
2.2E
-16
-0.1
79cl
osen
ess
cent
ralit
y10
.24
<2.
2E-1
60.
173
15.1
1<
2.2E
-16
0.22
917
.95
<2.
2E-1
60.
176
radi
ality
10.2
9<
2.2E
-16
0.17
415
.12
<2.
2E-1
60.
229
18.0
7<
2.2E
-16
0.17
8st
ress
10.5
0<
2.2E
-16
0.17
718
.18
<2.
2E-1
60.
275
25.7
8<
2.2E
-16
0.25
3to
polo
gica
lcoe
�ci
ent
-6.6
13.
87E
-11
-0.1
12-5
.53
3.22
E-0
8-0
.084
-6.4
98.
60E
-11
-0.0
64*c
orre
cted
for
exon
size
inba
sepa
irs;
**co
rrec
ted
for
sequ
ence
dex
onsi
zein
base
pair
s
215
Appendix D
[Tab
leD
.3co
ntin
ued]
Wilc
oxon
Rank
Sum
test
resu
ltsfo
rpa
ir-w
ise
com
pari
son
betw
een
the
gene
clas
ses
(–=
8.77
e-05
).A
posi
tive
Z-sc
ore
indi
cate
sth
atge
necl
ass
Aha
sa
high
erra
nkth
ange
necl
ass
Ban
da
nega
tive
Z-sc
ore
rin
dica
tes
that
sam
ple
Aha
sa
smal
ler
rank
than
gene
clas
sB
.
Mon
ogen
icvs
.C
ompl
exM
onog
enic
vs.
Non
-Ass
ocia
ted
Com
plex
vs.
Non
-Ass
ocia
ted
Z-sc
ore
P-v
alue
rZ-
scor
eP
-val
uer
Z-sc
ore
P-v
alue
r
gene
size
*-2
5.50
<2.
2E-1
6-0
.352
16.3
0<
2.2E
-16
0.13
641
.76
<2.
2E-1
60.
342
exon
size
-11.
80<
2.2E
-16
-0.1
6321
.92
<2.
2E-1
60.
183
34.2
5<
2.2E
-16
0.28
1#
uniq
ueex
ons*
3.18
1.48
E-0
30.
044
10.9
9<
2.2E
-16
0.09
28.
69<
2.2E
-16
0.07
1#
isof
orm
s-5
.54
3.06
E-0
8-0
.078
14.5
8<
2.2E
-16
0.12
321
.05
<2.
2E-1
60.
174
#ex
pres
sed
tiss
ues
-1.6
11.
08E
-01
-0.0
24-0
.71
4.80
E-0
1-0
.007
1.30
1.93
E-0
10.
012
sequ
ence
dex
onsi
ze-6
.92
4.56
E-1
2-0
.103
21.4
9<
2.2E
-16
0.19
928
.95
<2.
2E-1
60.
264
#co
mm
onva
rian
ts**
-3.7
61.
67E
-04
-0.0
56-4
.12
3.78
E-0
5-0
.038
-0.8
04.
23E
-01
-0.0
07#
rare
vari
ants
**-0
.32
7.47
E-0
1-0
.005
-4.1
23.
78E
-05
-0.0
38-4
.24
2.26
E-0
5-0
.039
#no
nsy
nony
mou
sva
rian
ts**
-0.7
44.
61E
-01
-0.0
11-3
.95
7.88
E-0
5-0
.037
-3.4
45.
73E
-04
-0.0
31#
mis
sens
eva
rian
ts**
-2.2
92.
23E
-02
-0.0
34-7
.89
2.91
E-1
5-0
.073
-6.1
01.
08E
-09
-0.0
56#
splic
eva
rian
ts**
-0.6
35.
31E
-01
-0.0
093.
741.
87E
-04
0.03
54.
526.
28E
-06
0.04
1
degr
ee8.
25<
2.2E
-16
0.12
715
.93
<2.
2E-1
60.
159
7.73
1.07
E-1
40.
076
clus
teri
ngco
e�ci
ent
3.53
4.14
E-0
40.
054
4.87
1.14
E-0
60.
049
1.52
1.29
E-0
10.
015
betw
eenn
ess
cent
ralit
y8.
36<
2.2E
-16
0.12
917
.52
<2.
2E-1
60.
175
9.23
<2.
2E-1
60.
091
ecce
ntri
city
-4.7
02.
61E
-06
-0.0
73-9
.62
<2.
2E-1
6-0
.096
-4.9
96.
01E
-07
-0.0
49cl
osen
ess
cent
ralit
y5.
311.
10E
-07
0.08
28.
37<
2.2E
-16
0.08
43.
141.
68E
-03
0.03
1ra
dial
ity5.
271.
38E
-07
0.08
18.
44<
2.2E
-16
0.08
43.
251.
15E
-03
0.03
2st
ress
8.36
6.48
E-1
70.
129
16.3
4<
2.2E
-16
0.16
38.
124.
44E
-16
0.08
0to
polo
gica
lcoe
�ci
ent
-0.1
68.
75E
-01
-0.0
02-1
.48
1.38
E-0
1-0
.015
-1.2
52.
12E
-01
-0.0
12*c
orre
cted
for
exon
size
inba
sepa
irs;
**co
rrec
ted
for
sequ
ence
dex
onsi
zein
base
pair
s
216