Correlation between copy number variation genes (focal) and selected clinical features
Bladder Urothelial Carcinoma (Primary solid tumor)
21 April 2013  |  analyses__2013_04_21
Maintainer Information
Citation Information
doi:10.7908/C1CC0XMH
Maintained by TCGA GDAC Team (Broad Institute/MD Anderson Cancer Center/Harvard Medical School)
Cite as Broad Institute TCGA Genome Data Analysis Center (2013): Bladder Urothelial Carcinoma (Primary solid tumor cohort) - 21 April 2013: Correlation between copy number variation genes (focal) and selected clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1CC0XMH
Overview
Introduction

This pipeline computes the correlation between significant copy number variation (cnv focal) genes and selected clinical features.

Summary

Testing the association between copy number variation 62 arm-level results and 11 clinical features across 131 patients, one significant finding detected with Q value < 0.25.

  • Amp Peak 8(4q13.3) cnv correlated to 'KARNOFSKY.PERFORMANCE.SCORE'.

Results
Overview of the results

Table 1.  Get Full Table Overview of the association between significant copy number variation of 62 arm-level results and 11 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, one significant finding detected.

Clinical
Features 		Time
to
Death 		AGE GENDER KARNOFSKY
PERFORMANCE
SCORE 		NUMBERPACKYEARSSMOKED TOBACCOSMOKINGHISTORYINDICATOR DISTANT
METASTASIS 		LYMPH
NODE
METASTASIS 		NUMBER
OF
LYMPH
NODES 		TUMOR
STAGECODE 		NEOPLASM
DISEASESTAGE
nCNV (%) nWild-Type logrank test t-test Fisher's exact test t-test t-test t-test Fisher's exact test Chi-square test t-test t-test Fisher's exact test
Amp Peak 8(4q13 3) 0 (0%) 114 0.522
(1.00) 		0.112
(1.00) 		0.0363
(1.00) 		7.05e-05
(0.0437) 		0.886
(1.00) 		0.714
(1.00) 		1
(1.00) 		0.727
(1.00) 		0.902
(1.00) 		0.622
(1.00)
Amp Peak 1(1p34 2) 0 (0%) 90 0.762
(1.00) 		0.246
(1.00) 		0.518
(1.00) 		0.193
(1.00) 		0.237
(1.00) 		0.825
(1.00) 		1
(1.00) 		0.593
(1.00) 		0.463
(1.00) 		0.583
(1.00)
Amp Peak 2(1p22 3) 0 (0%) 92 0.38
(1.00) 		0.174
(1.00) 		0.827
(1.00) 		0.671
(1.00) 		0.0722
(1.00) 		0.316
(1.00) 		0.297
(1.00) 		0.316
(1.00) 		0.184
(1.00) 		0.308
(1.00)
Amp Peak 3(1q21 3) 0 (0%) 63 0.432
(1.00) 		0.401
(1.00) 		0.691
(1.00) 		0.366
(1.00) 		0.0467
(1.00) 		0.673
(1.00) 		0.508
(1.00) 		0.131
(1.00) 		0.0852
(1.00) 		0.135
(1.00)
Amp Peak 4(1q23 3) 0 (0%) 59 0.638
(1.00) 		0.42
(1.00) 		0.423
(1.00) 		0.301
(1.00) 		0.242
(1.00) 		0.333
(1.00) 		0.314
(1.00) 		0.155
(1.00) 		0.0745
(1.00) 		0.0809
(1.00)
Amp Peak 5(3p25 2) 0 (0%) 68 0.0544
(1.00) 		0.491
(1.00) 		0.026
(1.00) 		0.0947
(1.00) 		0.921
(1.00) 		0.0413
(1.00) 		0.816
(1.00) 		0.777
(1.00) 		0.401
(1.00) 		0.532
(1.00)
Amp Peak 6(3q26 32) 0 (0%) 56 0.0481
(1.00) 		0.624
(1.00) 		0.839
(1.00) 		0.751
(1.00) 		0.871
(1.00) 		0.533
(1.00) 		0.847
(1.00) 		0.417
(1.00) 		0.921
(1.00) 		0.271
(1.00)
Amp Peak 7(4p16 3) 0 (0%) 104 0.0532
(1.00) 		0.61
(1.00) 		0.0805
(1.00) 		0.391
(1.00) 		0.444
(1.00) 		0.422
(1.00) 		0.0427
(1.00) 		0.174
(1.00) 		0.953
(1.00) 		0.0295
(1.00)
Amp Peak 9(5p15 1) 0 (0%) 67 0.753
(1.00) 		0.398
(1.00) 		0.232
(1.00) 		0.595
(1.00) 		0.365
(1.00) 		0.273
(1.00) 		0.247
(1.00) 		0.0269
(1.00) 		0.088
(1.00) 		0.596
(1.00)
Amp Peak 10(6p22 3) 0 (0%) 76 0.302
(1.00) 		0.367
(1.00) 		0.686
(1.00) 		0.703
(1.00) 		0.644
(1.00) 		0.451
(1.00) 		0.649
(1.00) 		0.865
(1.00) 		0.0136
(1.00) 		0.522
(1.00)
Amp Peak 11(6q12) 0 (0%) 109 0.409
(1.00) 		0.101
(1.00) 		0.28
(1.00) 		0.256
(1.00) 		0.126
(1.00) 		0.963
(1.00) 		0.496
(1.00) 		0.574
(1.00) 		0.0806
(1.00) 		0.176
(1.00)
Amp Peak 12(6q21) 0 (0%) 116 0.878
(1.00) 		0.384
(1.00) 		1
(1.00) 		0.364
(1.00) 		0.299
(1.00) 		0.808
(1.00) 		0.483
(1.00) 		0.882
(1.00) 		0.903
(1.00) 		1
(1.00)
Amp Peak 13(7p11 2) 0 (0%) 61 0.623
(1.00) 		0.058
(1.00) 		1
(1.00) 		0.688
(1.00) 		0.424
(1.00) 		0.527
(1.00) 		0.168
(1.00) 		0.826
(1.00) 		0.29
(1.00) 		0.623
(1.00)
Amp Peak 14(8p11 23) 0 (0%) 86 0.66
(1.00) 		0.897
(1.00) 		0.674
(1.00) 		0.866
(1.00) 		0.201
(1.00) 		0.7
(1.00) 		1
(1.00) 		0.844
(1.00) 		0.908
(1.00) 		0.735
(1.00)
Amp Peak 15(8p11 21) 0 (0%) 86 0.0139
(1.00) 		0.499
(1.00) 		0.205
(1.00) 		0.425
(1.00) 		0.0946
(1.00) 		0.166
(1.00) 		0.485
(1.00) 		0.82
(1.00) 		0.779
(1.00) 		0.506
(1.00)
Amp Peak 16(8q22 3) 0 (0%) 49 0.241
(1.00) 		0.968
(1.00) 		0.0629
(1.00) 		0.563
(1.00) 		0.233
(1.00) 		0.59
(1.00) 		0.0878
(1.00) 		0.413
(1.00) 		0.095
(1.00) 		0.602
(1.00)
Amp Peak 17(8q24 21) 0 (0%) 51 0.135
(1.00) 		0.709
(1.00) 		0.101
(1.00) 		0.595
(1.00) 		0.765
(1.00) 		0.823
(1.00) 		0.211
(1.00) 		0.731
(1.00) 		0.117
(1.00) 		0.151
(1.00)
Amp Peak 18(10p15 1) 0 (0%) 75 0.629
(1.00) 		0.0715
(1.00) 		1
(1.00) 		0.687
(1.00) 		0.7
(1.00) 		0.112
(1.00) 		0.4
(1.00) 		0.182
(1.00) 		0.539
(1.00) 		0.88
(1.00)
Amp Peak 19(11q13 3) 0 (0%) 80 0.843
(1.00) 		0.345
(1.00) 		0.682
(1.00) 		0.578
(1.00) 		0.445
(1.00) 		0.417
(1.00) 		0.0464
(1.00) 		0.155
(1.00) 		0.353
(1.00) 		0.608
(1.00)
Amp Peak 20(12q15) 0 (0%) 87 0.721
(1.00) 		0.971
(1.00) 		0.677
(1.00) 		0.592
(1.00) 		0.0724
(1.00) 		0.491
(1.00) 		0.231
(1.00) 		0.23
(1.00) 		0.501
(1.00) 		0.0146
(1.00)
Amp Peak 21(13q34) 0 (0%) 82 0.789
(1.00) 		0.548
(1.00) 		0.837
(1.00) 		0.654
(1.00) 		0.126
(1.00) 		0.0142
(1.00) 		1
(1.00) 		0.587
(1.00) 		0.554
(1.00) 		0.196
(1.00)
Amp Peak 22(16p12 1) 0 (0%) 96 0.564
(1.00) 		0.655
(1.00) 		1
(1.00) 		0.375
(1.00) 		0.991
(1.00) 		0.737
(1.00) 		1
(1.00) 		0.353
(1.00) 		0.99
(1.00) 		0.15
(1.00)
Amp Peak 23(17q11 2) 0 (0%) 69 0.747
(1.00) 		0.396
(1.00) 		0.842
(1.00) 		0.0164
(1.00) 		0.967
(1.00) 		0.924
(1.00) 		0.00971
(1.00) 		0.223
(1.00) 		0.68
(1.00) 		0.103
(1.00)
Amp Peak 24(17q12) 0 (0%) 75 0.281
(1.00) 		0.512
(1.00) 		1
(1.00) 		0.0578
(1.00) 		0.156
(1.00) 		0.176
(1.00) 		0.027
(1.00) 		0.57
(1.00) 		0.871
(1.00) 		0.312
(1.00)
Amp Peak 25(19q12) 0 (0%) 73 0.16
(1.00) 		0.421
(1.00) 		0.842
(1.00) 		0.498
(1.00) 		0.34
(1.00) 		0.644
(1.00) 		0.491
(1.00) 		0.57
(1.00) 		0.154
(1.00) 		0.516
(1.00)
Amp Peak 26(19q13 43) 0 (0%) 75 0.088
(1.00) 		0.5
(1.00) 		0.839
(1.00) 		0.479
(1.00) 		0.626
(1.00) 		0.787
(1.00) 		0.702
(1.00) 		0.343
(1.00) 		0.0772
(1.00) 		0.516
(1.00)
Amp Peak 27(20q11 21) 0 (0%) 39 0.793
(1.00) 		0.406
(1.00) 		1
(1.00) 		0.61
(1.00) 		0.0297
(1.00) 		0.707
(1.00) 		0.576
(1.00) 		0.341
(1.00) 		0.622
(1.00) 		0.571
(1.00)
Amp Peak 28(22q11 23) 0 (0%) 99 0.113
(1.00) 		0.397
(1.00) 		0.169
(1.00) 		0.684
(1.00) 		0.379
(1.00) 		0.482
(1.00) 		0.503
(1.00) 		0.764
(1.00) 		0.747
(1.00) 		0.796
(1.00)
Del Peak 1(1p36 11) 0 (0%) 108 0.134
(1.00) 		0.144
(1.00) 		1
(1.00) 		0.942
(1.00) 		0.679
(1.00) 		0.761
(1.00) 		1
(1.00) 		0.00706
(1.00) 		0.38
(1.00) 		0.282
(1.00)
Del Peak 2(1q32 1) 0 (0%) 106 0.663
(1.00) 		0.119
(1.00) 		0.0382
(1.00) 		0.666
(1.00) 		0.00608
(1.00) 		0.575
(1.00) 		0.487
(1.00) 		0.0544
(1.00) 		0.304
(1.00) 		0.333
(1.00)
Del Peak 3(2q22 1) 0 (0%) 91 0.204
(1.00) 		0.681
(1.00) 		0.125
(1.00) 		0.534
(1.00) 		0.992
(1.00) 		0.292
(1.00) 		0.42
(1.00) 		0.61
(1.00) 		0.624
(1.00) 		0.268
(1.00)
Del Peak 4(2q34) 0 (0%) 76 0.232
(1.00) 		0.293
(1.00) 		0.839
(1.00) 		0.632
(1.00) 		0.565
(1.00) 		0.396
(1.00) 		0.424
(1.00) 		0.522
(1.00) 		0.439
(1.00) 		0.937
(1.00)
Del Peak 5(2q37 1) 0 (0%) 64 0.355
(1.00) 		0.602
(1.00) 		0.0694
(1.00) 		0.433
(1.00) 		0.297
(1.00) 		0.163
(1.00) 		0.168
(1.00) 		0.882
(1.00) 		0.952
(1.00) 		0.769
(1.00)
Del Peak 6(3p21 31) 0 (0%) 89 0.76
(1.00) 		0.673
(1.00) 		0.667
(1.00) 		0.63
(1.00) 		0.684
(1.00) 		0.233
(1.00) 		1
(1.00) 		0.414
(1.00) 		0.257
(1.00) 		0.0274
(1.00)
Del Peak 7(3p14 2) 0 (0%) 88 0.543
(1.00) 		0.392
(1.00) 		0.67
(1.00) 		0.63
(1.00) 		0.48
(1.00) 		0.548
(1.00) 		0.573
(1.00) 		0.439
(1.00) 		0.0772
(1.00) 		0.139
(1.00)
Del Peak 8(3p12 3) 0 (0%) 94 0.798
(1.00) 		0.0607
(1.00) 		0.505
(1.00) 		0.105
(1.00) 		0.993
(1.00) 		0.377
(1.00) 		0.39
(1.00) 		0.763
(1.00) 		0.234
(1.00) 		0.302
(1.00)
Del Peak 9(4q22 1) 0 (0%) 79 0.825
(1.00) 		0.121
(1.00) 		0.304
(1.00) 		0.861
(1.00) 		1
(1.00) 		0.0216
(1.00) 		0.389
(1.00) 		0.739
(1.00) 		0.171
(1.00) 		1
(1.00)
Del Peak 10(4q34 2) 0 (0%) 72 0.338
(1.00) 		0.0777
(1.00) 		0.84
(1.00) 		0.631
(1.00) 		0.476
(1.00) 		0.377
(1.00) 		0.762
(1.00) 		0.601
(1.00) 		0.486
(1.00) 		0.364
(1.00)
Del Peak 11(5q11 2) 0 (0%) 63 0.735
(1.00) 		0.0156
(1.00) 		0.232
(1.00) 		0.338
(1.00) 		0.372
(1.00) 		0.734
(1.00) 		0.68
(1.00) 		0.0577
(1.00) 		0.262
(1.00) 		0.0266
(1.00)
Del Peak 12(5q35 1) 0 (0%) 65 0.509
(1.00) 		0.0914
(1.00) 		0.0724
(1.00) 		0.24
(1.00) 		0.506
(1.00) 		0.998
(1.00) 		0.446
(1.00) 		0.0839
(1.00) 		0.171
(1.00) 		0.0125
(1.00)
Del Peak 13(6p25 3) 0 (0%) 95 0.14
(1.00) 		0.825
(1.00) 		0.259
(1.00) 		0.154
(1.00) 		0.354
(1.00) 		0.635
(1.00) 		0.238
(1.00) 		0.0888
(1.00) 		0.0729
(1.00) 		0.224
(1.00)
Del Peak 14(6q21) 0 (0%) 76 0.107
(1.00) 		0.175
(1.00) 		0.839
(1.00) 		0.966
(1.00) 		0.826
(1.00) 		0.798
(1.00) 		0.779
(1.00) 		0.00186
(1.00) 		0.0031
(1.00) 		0.00253
(1.00)
Del Peak 15(8p23 1) 0 (0%) 57 0.559
(1.00) 		0.349
(1.00) 		0.0697
(1.00) 		0.907
(1.00) 		0.661
(1.00) 		0.938
(1.00) 		0.476
(1.00) 		0.682
(1.00) 		0.481
(1.00) 		0.506
(1.00)
Del Peak 16(9p23) 0 (0%) 73 0.651
(1.00) 		0.788
(1.00) 		0.549
(1.00) 		0.753
(1.00) 		0.661
(1.00) 		0.652
(1.00) 		0.789
(1.00) 		0.86
(1.00) 		0.57
(1.00) 		1
(1.00)
Del Peak 17(9p21 3) 0 (0%) 55 0.334
(1.00) 		0.771
(1.00) 		0.419
(1.00) 		0.975
(1.00) 		0.214
(1.00) 		0.728
(1.00) 		0.789
(1.00) 		0.272
(1.00) 		0.533
(1.00) 		0.43
(1.00)
Del Peak 18(10p12 1) 0 (0%) 104 0.966
(1.00) 		0.176
(1.00) 		1
(1.00) 		0.635
(1.00) 		0.932
(1.00) 		0.345
(1.00) 		0.597
(1.00) 		0.944
(1.00) 		0.328
(1.00) 		1
(1.00)
Del Peak 19(10q23 31) 0 (0%) 74 0.688
(1.00) 		0.00687
(1.00) 		1
(1.00) 		0.0916
(1.00) 		0.606
(1.00) 		0.719
(1.00) 		0.5
(1.00) 		0.275
(1.00) 		0.186
(1.00) 		0.443
(1.00)
Del Peak 20(11p15 5) 0 (0%) 65 0.409
(1.00) 		0.00881
(1.00) 		0.842
(1.00) 		0.00871
(1.00) 		0.869
(1.00) 		0.272
(1.00) 		1
(1.00) 		0.36
(1.00) 		0.182
(1.00) 		0.773
(1.00)
Del Peak 21(11q25) 0 (0%) 89 0.538
(1.00) 		0.537
(1.00) 		1
(1.00) 		0.966
(1.00) 		0.256
(1.00) 		0.718
(1.00) 		0.699
(1.00) 		0.698
(1.00) 		0.0475
(1.00) 		0.85
(1.00)
Del Peak 22(13q14 2) 0 (0%) 80 0.353
(1.00) 		0.0997
(1.00) 		0.303
(1.00) 		0.753
(1.00) 		0.696
(1.00) 		0.0343
(1.00) 		0.731
(1.00) 		0.895
(1.00) 		0.221
(1.00) 		0.344
(1.00)
Del Peak 23(14q12) 0 (0%) 94 0.378
(1.00) 		0.258
(1.00) 		0.181
(1.00) 		0.487
(1.00) 		0.0496
(1.00) 		0.428
(1.00) 		0.801
(1.00) 		0.12
(1.00) 		0.16
(1.00) 		0.151
(1.00)
Del Peak 24(14q32 31) 0 (0%) 93 0.676
(1.00) 		0.113
(1.00) 		0.0478
(1.00) 		0.312
(1.00) 		0.55
(1.00) 		0.707
(1.00) 		0.315
(1.00) 		0.963
(1.00) 		0.696
(1.00) 		0.496
(1.00)
Del Peak 25(15q13 1) 0 (0%) 82 0.205
(1.00) 		0.123
(1.00) 		0.407
(1.00) 		0.285
(1.00) 		0.62
(1.00) 		0.602
(1.00) 		0.129
(1.00) 		0.779
(1.00) 		0.452
(1.00) 		0.846
(1.00)
Del Peak 26(16p13 3) 0 (0%) 83 0.487
(1.00) 		0.258
(1.00) 		0.682
(1.00) 		0.862
(1.00) 		0.627
(1.00) 		0.368
(1.00) 		0.731
(1.00) 		0.759
(1.00) 		0.688
(1.00) 		0.276
(1.00)
Del Peak 27(16q23 1) 0 (0%) 94 0.213
(1.00) 		0.847
(1.00) 		0.658
(1.00) 		0.127
(1.00) 		0.823
(1.00) 		0.111
(1.00) 		0.341
(1.00) 		0.265
(1.00) 		0.213
(1.00) 		0.322
(1.00)
Del Peak 28(17p12) 0 (0%) 63 0.124
(1.00) 		0.478
(1.00) 		0.426
(1.00) 		0.827
(1.00) 		0.969
(1.00) 		0.689
(1.00) 		0.385
(1.00) 		0.166
(1.00) 		0.522
(1.00) 		0.0627
(1.00)
Del Peak 29(18q23) 0 (0%) 74 0.215
(1.00) 		0.088
(1.00) 		0.841
(1.00) 		0.125
(1.00) 		0.406
(1.00) 		0.525
(1.00) 		0.664
(1.00) 		0.992
(1.00) 		0.457
(1.00) 		0.937
(1.00)
Del Peak 30(19p13 3) 0 (0%) 80 0.609
(1.00) 		0.622
(1.00) 		1
(1.00) 		0.206
(1.00) 		0.187
(1.00) 		0.523
(1.00) 		0.15
(1.00) 		0.455
(1.00) 		0.544
(1.00) 		0.518
(1.00)
Del Peak 31(22q13 32) 0 (0%) 78 0.912
(1.00) 		0.35
(1.00) 		0.839
(1.00) 		0.0926
(1.00) 		0.868
(1.00) 		0.745
(1.00) 		0.0882
(1.00) 		0.926
(1.00) 		0.429
(1.00) 		0.522
(1.00)
Del Peak 32(Xp11 3) 0 (0%) 94 0.824
(1.00) 		0.17
(1.00) 		0.374
(1.00) 		0.785
(1.00) 		0.18
(1.00) 		0.704
(1.00) 		0.868
(1.00) 		0.179
(1.00) 		0.96
(1.00) 		0.0712
(1.00)
Del Peak 33(Xq21 33) 0 (0%) 100 0.446
(1.00) 		0.888
(1.00) 		1
(1.00) 		0.508
(1.00) 		0.634
(1.00) 		0.241
(1.00) 		0.286
(1.00) 		0.613
(1.00) 		0.929
(1.00) 		0.75
(1.00)
Del Peak 34(Xq23) 0 (0%) 101 0.423
(1.00) 		0.607
(1.00) 		1
(1.00) 		0.845
(1.00) 		0.835
(1.00) 		0.363
(1.00) 		0.758
(1.00) 		0.9
(1.00) 		0.941
(1.00) 		0.868
(1.00)
'Amp Peak 8(4q13.3)' versus 'KARNOFSKY.PERFORMANCE.SCORE'

P value = 7.05e-05 (t-test), Q value = 0.044

Table S1.  Gene #8: 'Amp Peak 8(4q13.3)' versus Clinical Feature #4: 'KARNOFSKY.PERFORMANCE.SCORE'

nPatients Mean (Std.Dev)
ALL 37 78.1 (16.3)
AMP PEAK 8(4Q13.3) CNV 3 90.0 (0.0)
AMP PEAK 8(4Q13.3) WILD-TYPE 34 77.1 (16.6)

Figure S1.  Get High-res Image Gene #8: 'Amp Peak 8(4q13.3)' versus Clinical Feature #4: 'KARNOFSKY.PERFORMANCE.SCORE'

Methods & Data
Input

  • Mutation data file = all_lesions.conf_99.cnv.cluster.txt

  • Clinical data file = BLCA-TP.clin.merged.picked.txt

  • Number of patients = 131

  • Number of significantly arm-level cnvs = 62

  • Number of selected clinical features = 11

  • Exclude genes that fewer than K tumors have mutations, K = 3

Survival analysis

For survival clinical features, the Kaplan-Meier survival curves of tumors with and without gene mutations were plotted and the statistical significance P values were estimated by logrank test (Bland and Altman 2004) using the 'survdiff' function in R

Student's t-test analysis

For continuous numerical clinical features, two-tailed Student's t test with unequal variance (Lehmann and Romano 2005) was applied to compare the clinical values between tumors with and without gene mutations using 't.test' function in R

Fisher's exact test

For binary or multi-class clinical features (nominal or ordinal), two-tailed Fisher's exact tests (Fisher 1922) were used to estimate the P values using the 'fisher.test' function in R

Chi-square test

For multi-class clinical features (nominal or ordinal), Chi-square tests (Greenwood and Nikulin 1996) were used to estimate the P values using the 'chisq.test' function in R

Q value calculation

For multiple hypothesis correction, Q value is the False Discovery Rate (FDR) analogue of the P value (Benjamini and Hochberg 1995), defined as the minimum FDR at which the test may be called significant. We used the 'Benjamini and Hochberg' method of 'p.adjust' function in R to convert P values into Q values.

Download Results

This is an experimental feature. The full results of the analysis summarized in this report can be downloaded from the TCGA Data Coordination Center.

References
[1] Bland and Altman, Statistics notes: The logrank test, BMJ 328(7447):1073 (2004)
[2] Lehmann and Romano, Testing Statistical Hypotheses (3E ed.), New York: Springer. ISBN 0387988645 (2005)
[3] Fisher, R.A., On the interpretation of chi-square from contingency tables, and the calculation of P, Journal of the Royal Statistical Society 85(1):87-94 (1922)
[4] Greenwood and Nikulin, A guide to chi-squared testing, Wiley, New York. ISBN 047155779X (1996)
[5] Benjamini and Hochberg, Controlling the false discovery rate: a practical and powerful approach to multiple testing, Journal of the Royal Statistical Society Series B 59:289-300 (1995)
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