Somatic loss of BRCA1 and p53 in mice induces mammary tumors with features of human BRCA1-mutated basal-like breast cancer -- Liu et al. 104 (29): 12111 Data Supplement - HTML Page - index.htslp -- Proceedings of the National Academy of Sciences

Liu et al. 10.1073/pnas.0702969104.

Supporting Information

Files in this Data Supplement:

SI Figure 7
SI Table 2
SI Table 3
SI Figure 8
SI Table 4
SI Table 5
SI Figure 9
SI Figure 10
SI Figure 11
SI Table 6
SI Materials and Methods

SI Figure 7

Fig. 7. Generation of the conditional Brca1 allele. (A) Schematic representations of the Brca1 locus, the 3' targeting vector, the Brca1 allele with a loxP site in intron 13, the 5' targeting vector, and the final Brca1allele with loxP sites in introns 3 and 13, respectively. The exon 11 and exon 14 probes for Southern hybridizations are indicated. Primers P1-P4 are used for detection of both loxP sites and for detecting the deletion of exons 5-13. (B) Southern blot analysis of BglII-digested DNA from Brca1^+/+, Brca1^F/+, Brca1^F/F, Brca1D^/F, and Brca1D^/+ mice using a Brca1 5' flanking probe. (C) Southern blot analysis of EcoRV + StuI-digested DNA from Brca1^+/+, Brca1^F/+, Brca1^F/F, Brca1D^/F, and Brca1D^/+ mice using a Brca1 exon 14 probe. (D) PCR analysis of DNA from Brca1^+/+, Brca1^F/+, Brca1^F/F, and Brca1D^/F mice using primers P1 and P2 for detection of the loxP site in Brca1 intron 3 (Left) and primers P1 and P4 for detection of the Brca1D allele (Right).

SI Figure 8

Fig. 8. Unsupervised hierarchical clustering of mouse mammary tumors. Unsupervised hierarchical clustering of 32 mouse mammary tumors from K14cre;Brca1^F/F;p53^F/F female mice and 21 tumors from K14cre;p53^F/F female mice. A hierarchical clustering algorithm based on Pearson correlation coefficients was applied to group genes according to similarity in the pattern of gene expression over all tumors and tumors according to similarity in the pattern of gene expression over all genes.

Fig. 9. Gene ontology (GO) analysis of mouse Brca1 classifier genes. GO analysis of mouse BRCA1 reporter genes was performed using Gene Set Analysis Toolkit software (www.bioinfo.vanderbilt.edu/webgestalt). Only GO sets containing three or more BRCA1 reporter genes were included in the analysis The enriched GO categories (hypergeometric; P < 0.01; red) and their nonenriched parents (black) were visualized by directed acyclic graphs for the 646 mouse BRCA1 reporter genes.

SI Figure 10

Fig. 10. Unsupervised hierarchical clustering of mouse and human breast cancers. Human breast cancer samples from 16 BRCA1 mutation carriers (pink) and 28 sporadic estrogen receptor (ER)-negative cases (gray) were compared with 32 mammary tumors from K14cre;Brca1^F/F;p53^F/F female mice (orange) and 21 tumors from K14cre;p53^F/F female mice (blue) by unsupervised hierarchical clustering. A hierarchical clustering algorithm based on Pearson correlation coefficients was applied to group genes according to similarity in the pattern of gene expression over all tumors and tumors according to similarity in the pattern of gene expression over all genes.

SI Figure 11

Fig. 11. Cross-species comparison of mouse and human BRCA1-mutated breast cancers by GSEA. Scatter plots of the subramanian maximum enrichment scores (MESs) for 980 gene sets of the GO hierarchy (A) and 424 gene sets of the MSigDb C2 pathways database (B), respectively. Gene sets were selected from the GO and/or MSigDb gene set collections when they contained at least five genes from the list of 7,127 nonredundant genes, which were represented on both mouse and human microarray platforms and annotated in the GO and/or MSigDb gene sets. The higher the MES, the stronger the association between the expression of the genes in a given gene set and the class label. The horizontal axis depicts the MES values for the association of the gene expression in the mouse tumors with the class labels (Brca1D^/D;p53D^/D vs. p53D^/D), whereas the vertical axis depicts the MES values for the association of the gene expression in the human tumors with the class labels (BRCA1-mutated vs. sporadic ER-negative). The color scales depict log₁₀ values of the gene set sizes.

Table 2. Histopathology of K14cre;p53^F/F mammary tumors

Tumor ID	Growth pattern	Borders	Mitotic count	Immunostaining				Tumor type	Grade	Array ID	Supervised classification
Tumor ID	Growth pattern	Borders	Mitotic count	CK8	Vim	Cyclin-D1	ER	Tumor type	Grade	Array ID	Supervised classification
01JOS65	S	Exp	++	+/-	+	-	-	Carcinosarcoma	III	Mm-p53-01	Validation
01JOS66	S	Exp	++	+	+	-	-	Carcinosarcoma	III	Mm-p53-02	Validation
01JOS80_1	S	Exp	++	+/-	+	+/-	-	Carcinosarcoma	III	Mm-p53-03	Validation
01JOS80_2	S	Exp	++	+/-	+	+/-	-	Carcinosarcoma	III	Mm-p53-04	Validation
01JOS127	N	Exp	+	+	-	+	-	Carcinoma	III	Mm-p53-05	Training
01JOS165	S, N	Exp	+/++	+	+/-	+	-	Carcinoma	III	Mm-p53-06	Training
01JOS169	Pap	Exp	+/-	-	-	+	+/-	Adenomyoepithelioma	I	Mm-p53-07	Training
01JOS181_1	S	Exp	+	++	n.d.	n.d.	-	Carcinoma	III	Mm-p53-08	Training
01JOS181_2	S	Exp	++	++	-	+/-	-	Carcinoma	III	Mm-p53-09	Training
02JOS92	S	Exp	++	-	+	+/-	-	Carcinosarcoma	III	Mm-p53-10	Validation
03JOS03	S	Inv	++	-	+	+/-	-	Carcinosarcoma	III	Mm-p53-11	Validation
03JOS14	S	Inv	++	-	+	+/-	-	Carcinosarcoma	III	Mm-p53-12	Validation
03JOS29	S	Exp	++	-	+	++	-	Carcinosarcoma	III	Mm-p53-13	Validation
03JOS105	S, N	Exp	++	+	-	-	+/-	Carcinoma	III	Mm-p53-14	Training
03JOS154_1	S, N	Exp	++	-	+	++	-	Carcinosarcoma	III	Mm-p53-15	Validation
03JOS154_2	S,	Inv	++	-	+	+/-	-	Carcinosarcoma	III	Mm-p53-16	Validation
03JOS154_3	Pap	Exp	++	+	-	+	-	Adenomyoepithelioma	I	Mm-p53-17	Training
03JOS155_1	Pap	Exp	++	+	-	+	-	Adenomyoepithelioma	I	Mm-p53-18	Training
03JOS155_2	S	Exp	++	+	-	-	-	Carcinoma	III	Mm-p53-19	Training
04LIU28	S	Exp	++	+	-	+/-	-	Carcinoma	III	Mm-p53-20	Training
04LIU54	S	Exp	++	+	-	+	-	Carcinoma	III	Mm-p53-21	Validation

Growth pattern: N, nested; Pap, papillary; S, solid. Borders: Exp, expansive; Inv, invasive.

Immunostaining: CK8, cytokeratin-8; Vim, vimentin; ER, estrogen receptor-a.

Positivity: -, 0%; +/-, 1-25%; +, 25-75%; ++, >75%; n.d., not determined.

Tumor grade: I, well differentiated; II, intermediate differentiation; III, poorly differentiated.

Table 3. Histopathology of K14cre;Brca1^F/F;p53^F/F mammary tumors

Tumor ID	Growth pattern	Borders	Mitotic count	Immunostaining				Tumor type	Grade	Array ID	Supervised classification
Tumor ID	Growth pattern	Borders	Mitotic count	CK8	Vim	Cyclin-D1	ER	Tumor type	Grade	Array ID	Supervised classification
00JOS88	S	Exp	++	++ L	+	+	-	Carcinosarcoma	III	Mm-Br1-01	Validation
00JOS94	S	Exp	++	-	+/-	+	-	Carcinoma	III	Mm-Br1-02	Training
00JOS135	S	Exp	-	+/-	-	++	-	Carcinoma	III	Mm-Br1-03	Training
00JOS164_1	S	Exp	++	-	-	++	-	Carcinoma	III	Mm-Br1-04	Validation
00JOS164_2	S	Exp	++	+	-	++	-	Carcinoma	III	Mm-Br1-05	Training
01JOS06	S, N	Exp	+	+ L	-	-	-	Adenomyoepithelioma	I	Mm-Br1-06	Validation
01JOS08	S	Exp	++	+	+	+	-	Carcinoma	III	Mm-Br1-07	Training
01JOS13	S, N	Inv	+	+/-	-	+/-	-	Carcinoma	II	Mm-Br1-08	Validation
01JOS20	S	Exp	++	+ L	+/-	+/-	-	Carcinoma	III	Mm-Br1-09	Training
01JOS25	N	Exp	+	-	-	+/-	-	Carcinoma	II	Mm-Br1-10	Validation
01JOS45	S	Exp	++	+/-	+/-	+/-	+/-	Carcinoma	II	Mm-Br1-11	Training
01JOS47	S, N	Exp	++	+	+/-	+/-	-	Carcinoma	III	Mm-Br1-12	Validation
01JOS94	S, N	Exp	++	+/-	-	+/-	-	Carcinoma	III	Mm-Br1-13	Training
03JOS117	S	Exp	++	+ L	-	+/-	-	Carcinoma	III	Mm-Br1-14	Validation
03JOS140	S	Exp	++	+/-	-	+	-	Carcinoma	II	Mm-Br1-15	Training
03JOS171	S	Exp	++	+	+/-	-	-	Carcinoma	III	Mm-Br1-16	Validation
03JOS174	S	Exp	++	+/-	-	+	-	Carcinoma	III	Mm-Br1-17	Training
03JOS242	S	Exp	+	++	-	+/-	+/-	Adenomyoepithelioma	I	Mm-Br1-18	Validation
03JOS272	S	Exp	++	+/-	-	+/-	-	Carcinoma	III	Mm-Br1-19	Training
04JOS09	S	Exp	++	+	+/-	+	-	Carcinoma	III	Mm-Br1-20	Validation
04JOS10	S	Exp	++	+	+/-	+	-	Carcinoma	III	Mm-Br1-21	Training
04JOS22	S	Exp	++	+/-		+	-	Carcinoma	II	Mm-Br1-22	Training
04LIU17	S, N	Exp	++	++	-	+/-	-	Carcinoma	II	Mm-Br1-23	Validation
04LIU55	S	Exp	++	+	-	+	-	Carcinoma	III	Mm-Br1-24	Validation
04LIU56	S	Exp	++	+	-	+	-	Carcinoma	III	Mm-Br1-25	Training
04LIU59	S	Exp	++	+	-	+/-	-	Carcinoma	III	Mm-Br1-26	Validation
04LIU61	S	Exp	++	+/-	-	+/-	-	Carcinoma	III	Mm-Br1-27	Training
04LIU62	S	Exp	++	+	-	+	-	Carcinoma	II	Mm-Br1-28	Validation
04LIU65	S	Exp	++	-	-	+/-	-	Carcinoma	III	Mm-Br1-29	Validation
04LIU66	S	Exp	+	+/-	-	+/-	-	Carcinoma	III	Mm-Br1-30	Training
04LIU73	S	Exp	++	+/-	-	+	-	Carcinoma	III	Mm-Br1-31	Validation
05LIU02	S	Exp	++	+	-	+/-	-	Carcinoma	II	Mm-Br1-32	Training

Growth pattern: N, nested; Pap, papillary; S, solid. Borders: Exp, expansive; Inv, invasive.

Immunostaining: CK8, cytokeratin-8; Vim, vimentin; ER, estrogen receptor-a; L, localized staining.

Positivity: -, 0%; +/-, 1-25%; +, 25-75%; ++, >75%; n.d., not determined.

Tumor grade: I, well differentiated; II, intermediate differentiation; III, poorly differentiated.

Table 4. List of 646 mouse BRCA1 reporter genes

	ENSMUSG ID	Gene symbol	D value	Stdev	Rawp	Q value	R fold
1	00000032968	Inha	9.003613958	0.183956175	0	0	3.114960924
2	00000020573	Pik3cg	-7.650069184	0.116218133	6.73E-08	0.000248346	0.545656234
3	00000043022	Aff1	-7.424544668	0.114013225	1.01E-07	0.000248346	0.553351233
4	00000021156	Zmynd11	7.392794827	0.098660684	1.12E-07	0.000248346	1.66275029
5	00000041028	Ghitm	-7.362412049	0.120802854	1.18E-07	0.000248346	0.531185043
6	00000023186	Loh11cr2a	-7.207038116	0.131204735	1.57E-07	0.00027594	0.521102402
7	00000039047	Pigk	-7.1018623	0.084670497	1.96E-07	0.00029565	0.65770699
8	00000025544	Tm9sf2	--6.948203145	0.119850443	3.03E-07	0.000399128	0.55850629
9	00000030217	Art4	6.83914137	0.283031642	4.04E-07	0.000425736	3.635051891
10	00000027207	Galk2	-6.821980391	0.129442797	4.04E-07	0.000425736	0.543498014
11	00000005893	Nr2c2	6.751066607	0.105798553	5.16E-07	0.000468113	1.700607468
12	00000042312	S100a13	-6.743587919	0.129410015	5.33E-07	0.000468113	0.561796876
13	00000036169	Sostdc1	6.662573173	0.426377451	6.17E-07	0.000500331	5.46615453
14	00000016458	Wt1	-6.585373218	0.086419396	7.18E-07	0.000540618	0.678490964
15	00000031931	Ankrd49	6.442099366	0.11402716	9.70E-07	0.000643039	1.699120004
16	00000001418	0610031J06Rik	-6.436908905	0.136787913	9.76E-07	0.000643039	0.555730729
17	00000045659	n.d.	6.405108998	0.190502096	1.04E-06	0.000643474	2.416968744
18	00000005803	Sqrdl	-6.337384508	0.290674621	1.19E-06	0.000696421	0.282415962
19	00000046342	n.d.	6.321243473	0.084897239	1.26E-06	0.000697112	1.46567844
20	00000051515	n.d.	6.250543488	0.161807676	1.47E-06	0.000707371	2.106309632
21	00000022394	L3mbtl2	6.249048308	0.084038838	1.48E-06	0.000707371	1.470680971
22	00000033970	Rfc3	6.220279154	0.115244835	1.57E-06	0.000707371	1.677058651
23	00000000861	Bcl11a	6.207822533	0.36190473	1.63E-06	0.000707371	4.357341496
24	00000030216	Wbp11	6.197380433	0.12344505	1.68E-06	0.000707371	1.735125568
25	00000022191	Rnasen	6.183554092	0.064805724	1.74E-06	0.000707371	1.321010207
26	00000039005	Tlr4	-6.171427604	0.202824611	1.80E-06	0.000707371	0.409986746
27	00000033257	Ttll4	6.16858912	0.120136824	1.81E-06	0.000707371	1.715916712
28	00000033257	Ttll4	6.117200414	0.109590051	2.02E-06	0.000762355	1.609092967
29	00000050534	Htr5b	6.040051174	0.223332575	2.43E-06	0.000881038	2.774297171
30	00000048387	Osr1	6.024306551	0.247130966	2.51E-06	0.000881038	3.173598751
31	00000020399	Havcr2	-6.008794326	0.068572381	2.63E-06	0.000894581	0.753066229
32	00000020471	Pold2	5.948319136	0.135216823	3.02E-06	0.000994124	1.796198816
33	00000030138	Bms1l	5.854793187	0.098125402	3.85E-06	0.00123098	1.525024703
34	00000041577	Prelp	5.831994333	0.204784609	4.09E-06	0.001267818	2.432559615
35	00000066842	n.d.	5.783400932	0.132516098	4.59E-06	0.001371178	1.774952395
36	00000035049	AA408556	5.772563333	0.095952591	4.72E-06	0.001371178	1.488567568
37	00000024735	Prpf19	5.761783964	0.127455128	4.81E-06	0.001371178	1.655792076
38	00000029465	Arpc3	-5.751138181	0.100213098	4.95E-06	0.001373996	0.683230703
39	00000028048	Gba	-5.675481378	0.137513713	5.99E-06	0.001488535	0.584508437
40	00000039577	Nphp4	5.673066071	0.095240366	6.01E-06	0.001488535	1.477269169
41	00000022422	2600005O03Rik	5.668317671	0.115681197	6.08E-06	0.001488535	1.585461849
42	00000028164	Manba	-5.659069462	0.185508045	6.18E-06	0.001488535	0.483759137
43	00000025321	n.d.	5.653540511	0.26514776	6.24E-06	0.001488535	3.245719366
44	00000043629	1700019D03Rik	5.644782489	0.216661442	6.35E-06	0.001488535	2.644898293
45	00000041491	Cep78	5.633555009	0.114068492	6.49E-06	0.001488535	1.559100677
46	00000031939	n.d.	5.632754452	0.156879896	6.49E-06	0.001488535	1.896405147
47	00000032035	n.d.	5.597175627	0.124597922	7.04E-06	0.001580157	1.665855551
48	00000030177	Ccdc77	5.584735638	0.139882284	7.26E-06	0.00159528	1.802526773
49	00000027195	Hsd17b12	-5.559020462	0.078988459	7.68E-06	0.001653228	0.738625906
50	00000046337	1700024G10Rik	5.544715104	0.182212091	7.94E-06	0.001674563	2.21419266
51	00000025821	Zfp282	5.536618907	0.11834381	8.14E-06	0.001682308	1.654372733
52	00000041939	Mvk	5.527949434	0.083131701	8.32E-06	0.001687481	1.392734789
53	00000034610	Zcchc11	5.5189757	0.225210405	8.54E-06	0.001690682	2.409379612
54	00000028433	Ubap2	5.515400939	0.067050575	8.66E-06	0.001690682	1.293876138
55	00000042810	A930040G15Rik	5.500762813	0.141312852	8.94E-06	0.001713697	1.754230428
56	00000028488	Sh3gl2	5.495063068	0.108450212	9.10E-06	0.001713716	1.570452463
57	00000049246	Hspe1-rs1	5.473961383	0.101933522	9.61E-06	0.001777014	1.483750614
58	00000022110	Sucla2	-5.45795526	0.149577269	9.97E-06	0.001812642	0.579576372
59	00000031351	Zfp185	5.431563477	0.185311091	1.07E-05	0.001892162	2.122788678
60	00000038349	Plcl1	5.417478297	0.40075418	1.11E-05	0.001892162	4.984965874
61	00000035235	Trim13	5.412956277	0.132572334	1.12E-05	0.001892162	1.656856767
62	00000041560	Gltscr2	5.399195804	0.165012243	1.16E-05	0.001892162	1.850522541
63	00000049553	Rpo1-4	5.398600824	0.173767023	1.16E-05	0.001892162	2.117177741
64	00000014245	Pigl	5.396478662	0.087518448	1.16E-05	0.001892162	1.410575552
65	00000042289	Hsd3b7	-5.395168697	0.1539987	1.17E-05	0.001892162	0.560888878
66	00000066952	Myo1h	-5.366194778	0.18575689	1.24E-05	0.001981286	0.524742863
67	00000025788	2810013C04Rik	5.360270027	0.083736427	1.26E-05	0.001981286	1.382335447
68	00000022360	Atad2	5.353918471	0.202197144	1.28E-05	0.001981286	2.151417247
69	00000027883	Gpsm2	5.347776926	0.122775898	1.30E-05	0.001981286	1.590478057
70	00000042188	n.d.	5.301872574	0.079635141	1.47E-05	0.002219912	1.356549511
71	00000035085	1700020L24Rik	-5.293855484	0.055016326	1.51E-05	0.002227232	0.819331455
72	00000022969	Il10rb	-5.291672332	0.173352983	1.52E-05	0.002227232	0.534785129
73	00000015790	Surf1	-5.257698449	0.116985355	1.65E-05	0.002322411	0.657210088
74	00000020642	Rnf144	5.252200865	0.154140914	1.66E-05	0.002322411	1.808893488
75	00000026020	Nol5	5.251187559	0.154242983	1.67E-05	0.002322411	1.810580736
76	00000042737	Dpm3	-5.249843001	0.055876666	1.67E-05	0.002322411	0.818431698
77	00000039007	Pgcp	-5.228904094	0.198740423	1.76E-05	0.00237132	0.496187338
78	00000003546	Klc4	-5.225824011	0.109751146	1.77E-05	0.00237132	0.68560952
79	00000042729	Wdr74	5.213196178	0.081171662	1.82E-05	0.00237132	1.352967703
80	00000031145	Lmo6	5.211550591	0.137878451	1.83E-05	0.00237132	1.695378017
81	00000033216	Eefsec	5.207700891	0.140545913	1.85E-05	0.00237132	1.718292378
82	00000040363	Bcor	5.204812192	0.077753012	1.86E-05	0.00237132	1.339555814
83	00000027803	Wwtr1	-5.200767778	0.14926386	1.88E-05	0.00237132	0.591541901
84	00000024349	2610307O08Rik	-5.197316687	0.20356625	1.90E-05	0.00237132	0.47023544
85	00000036632	Alg5	-5.18775592	0.15543547	1.94E-05	0.00237132	0.586831474
86	00000055805	Fmnl1	-5.186713767	0.180925976	1.95E-05	0.00237132	0.496382848
87	00000026822	Lcn2	-5.185263672	0.384807629	1.96E-05	0.00237132	0.361296248
88	00000040463	Mybbp1a	5.175531158	0.159475044	2.01E-05	0.002396429	1.846796291
89	00000042750	Bex2	5.173105849	0.149201611	2.02E-05	0.002396429	1.720513708
90	00000064326	Siva	5.163854584	0.171843318	2.06E-05	0.002417763	1.851315456
91	00000038637	Lrrc56	5.15270066	0.134628662	2.12E-05	0.002452923	1.700528731
92	00000043234	n.d.	5.141319654	0.079500206	2.17E-05	0.002471382	1.335625199
93	00000045694	n.d.	5.14017321	0.111709882	2.18E-05	0.002471382	1.51163694
94	00000044339	Alkbh2	5.103331195	0.117352993	2.41E-05	0.002702999	1.505319247
95	00000033728	Lrrc14	5.08275868	0.103251368	2.54E-05	0.00279328	1.467973459
96	00000021221	Dpf3	-5.081190698	0.25803695	2.54E-05	0.00279328	0.443129564
97	00000026723	Dnmt2	5.077783762	0.167745641	2.57E-05	0.002794353	1.932802228
98	00000024177	Nme4	5.066284628	0.131988737	2.65E-05	0.002813654	1.584342613
99	00000000439	Mkrn2	5.064455161	0.089509652	2.67E-05	0.002813654	1.390898144
100	00000041560	Gltscr2	5.060929641	0.174722907	2.69E-05	0.002813654	1.858240527
101	00000068206	Pick1	5.060278466	0.170137585	2.70E-05	0.002813654	1.897969068
102	00000045078	2810055G22Rik	5.048604671	0.116219622	2.78E-05	0.002842748	1.545247694
103	00000032359	Ctsh	-5.04617187	0.264246955	2.79E-05	0.002842748	0.396308776
104	00000024833	Pola2	5.044735205	0.114759132	2.81E-05	0.002842748	1.491432347
105	00000025001	Hells	5.041358913	0.129543991	2.83E-05	0.002842748	1.643121368
106	00000031592	Pcm1	5.03733701	0.105779147	2.86E-05	0.002844937	1.470914361
107	00000025875	Tspan17	-5.030013511	0.125619358	2.91E-05	0.002846261	0.657353967
108	00000042436	n.d.	-5.018541135	0.188342617	2.99E-05	0.002846261	0.516687448
109	00000025384	2310003H01Rik	5.014476528	0.113382816	3.01E-05	0.002846261	1.513067735
110	00000026822	Lcn2	-5.008175136	0.309151669	3.07E-05	0.002846261	0.424364198
111	00000029868	Trpv6	5.006919485	0.324452453	3.08E-05	0.002846261	2.697510158
112	00000040621	BC023488	4.999014908	0.118522463	3.14E-05	0.002846261	1.559646984
113	00000020363	Gfpt2	-4.998694145	0.185822106	3.14E-05	0.002846261	0.543041949
114	00000034269	Setd5	4.997669422	0.101894463	3.15E-05	0.002846261	1.451747539
115	00000025809	Itgb1	-4.997414547	0.189167847	3.15E-05	0.002846261	0.525617883
116	00000071711	Mpst	4.997352895	0.141305616	3.16E-05	0.002846261	1.669037126
117	00000024747	Aldh1a7	4.995708028	0.445707593	3.16E-05	0.002846261	7.931696828
118	00000051437	4922504M18Rik	-4.992428365	0.086266317	3.19E-05	0.002846261	0.743776422
119	00000049774	n.d.	-4.98857733	0.113753582	3.22E-05	0.002850169	0.68579679
120	00000025321	n.d.	4.953673645	0.177539017	3.51E-05	0.003077695	1.978267613
121	00000050393	n.d.	4.950180674	0.095642732	3.53E-05	0.003077695	1.395445432
122	00000039735	Fnbp1l	4.925145702	0.142294573	3.75E-05	0.003244884	1.698098824
123	00000041117	n.d.	4.918925565	0.087467301	3.81E-05	0.003268499	1.37414859
124	00000039354	Smarcal1	4.909362221	0.081467658	3.90E-05	0.00331796	1.322320978
125	00000024143	Rhoq	-4.904863347	0.230469463	3.95E-05	0.003330055	0.452426881
126	00000031078	Cttn	-4.902631555	0.128538901	3.98E-05	0.003330055	0.639603058
127	00000033107	Rnf125	-4.879047707	0.077840404	4.23E-05	0.003494326	0.765440926
128	00000025224	Gbf1	4.868724391	0.097128786	4.34E-05	0.003494326	1.389571777
129	00000000708	Pcaf	-4.861942784	0.17010585	4.41E-05	0.003494326	0.560903851
130	00000036781	Rps27l	-4.860977808	0.124317137	4.42E-05	0.003494326	0.655292308
131	00000063889	Crem	-4.859531593	0.197299831	4.44E-05	0.003494326	0.520530249
132	00000037720	Tmem33	-4.857917552	0.0741862	4.45E-05	0.003494326	0.782807088
133	00000022420	Dnalc4	4.856029547	0.073953807	4.47E-05	0.003494326	1.289506232
134	00000025477	Inpp5a	-4.854112006	0.083375219	4.50E-05	0.003494326	0.767302845
135	00000000441	Raf1	4.85388643	0.077084369	4.50E-05	0.003494326	1.306611623
136	00000047538	n.d.	4.853734333	0.146091645	4.51E-05	0.003494326	1.632324446
137	00000059866	Tnip2	-4.84388057	0.105203308	4.62E-05	0.003558087	0.71511616
138	00000026000	Lancl1	4.841515799	0.094358745	4.66E-05	0.003558087	1.416868017
139	00000027405	Nol5a	4.825408618	0.123886107	4.85E-05	0.003681378	1.52166212
140	00000021066	Spg3a	4.820099893	0.202149316	4.91E-05	0.003700275	2.170553199
141	00000056492	Gpr116	-4.808633915	0.133091508	5.05E-05	0.003775518	0.634072159
142	00000046791	2410016O06Rik	4.804792866	0.113141851	5.10E-05	0.003784324	1.521883994
143	00000020918	Gcn5l2	4.800628984	0.115251516	5.14E-05	0.003791767	1.486821348
144	00000026260	Ndufa10	4.794891291	0.103315156	5.22E-05	0.00380349	1.417933362
145	00000047534	C79407	4.794091491	0.111023219	5.23E-05	0.00380349	1.462228861
146	00000023571	C1qdc2	4.785306645	0.170847573	5.34E-05	0.003853579	1.818816342
147	00000028813	n.d.	4.772923065	0.062918099	5.51E-05	0.003943336	1.246632058
148	00000031591	Asah1	-4.771483487	0.239408961	5.53E-05	0.003943336	0.443654405
149	00000039835	5730409E15Rik	4.768535888	0.123964776	5.58E-05	0.003951793	1.573575249
150	00000044231	Nhlrc1	4.760528529	0.113719337	5.72E-05	0.00401967	1.487154768
151	00000000416	Cttnbp2	4.758105361	0.374698252	5.76E-05	0.00401967	3.865826588
152	00000050514	n.d.	4.750937108	0.11621951	5.87E-05	0.00406986	1.488265818
153	00000050220	n.d.	4.748398637	0.073003673	5.91E-05	0.004071086	1.272760753
154	00000045398	n.d.	4.740659544	0.121653244	6.03E-05	0.004123943	1.512092677
155	00000043858	Nup62	4.738085441	0.104262272	6.08E-05	0.004123943	1.418441449
156	00000046554	n.d.	4.736476551	0.099682283	6.10E-05	0.004123943	1.416264358
157	00000005469	Prkaca	-4.730089702	0.116386272	6.21E-05	0.004157817	0.702079836
158	00000039671	Prkcbp1	4.728358284	0.237706149	6.23E-05	0.004157817	2.553261573
159	00000021996	Esd	-4.724659922	0.219397106	6.29E-05	0.004169971	0.492164505
160	00000022770	Dlgh1	-4.719963044	0.106390012	6.36E-05	0.004182905	0.710108687
161	00000022455	4930521I23Rik	4.717567165	0.156443512	6.40E-05	0.004182905	1.81781739
162	00000020846	1500005K14Rik	4.715901023	0.214793317	6.43E-05	0.004182905	2.006556245
163	00000032330	Cox7a2	-4.712418925	0.097070146	6.50E-05	0.004198235	0.738047497
164	00000017861	Mybl2	4.710682995	0.145447139	6.53E-05	0.004198235	1.632877474
165	00000043175	n.d.	-4.701208176	0.086535441	6.70E-05	0.004245887	0.761582636
166	00000051303	Cdk2ap1	4.695125793	0.096954458	6.80E-05	0.004245887	1.379339668
167	00000061527	Krt2-5	4.694811079	0.601888586	6.81E-05	0.004245887	3.517869025
168	00000022554	Brp16	4.693615894	0.102815963	6.83E-05	0.004245887	1.424124112
169	00000026236	C130036L24Rik	4.692956391	0.112260029	6.84E-05	0.004245887	1.489146281
170	00000020930	1700039D13Rik	4.692596191	0.113863527	6.85E-05	0.004245887	1.49531549
171	00000018965	Ywhah	-4.689038829	0.115414196	6.90E-05	0.00425529	0.688060478
172	00000024791	Cdca5	4.683191158	0.08064142	7.02E-05	0.004286417	1.319793438
173	00000004609	n.d.	-4.682573582	0.08743417	7.03E-05	0.004286417	0.757097894
174	00000032625	Gm837	-4.679745233	0.117690117	7.08E-05	0.004290668	0.704908286
175	00000036934	4921524J17Rik	-4.670066822	0.081952704	7.26E-05	0.004372922	0.7739218
176	00000026434	Nucks1	4.663136915	0.131537845	7.39E-05	0.004399875	1.523650053
177	00000039835	5730409E15Rik	4.661741314	0.149144718	7.42E-05	0.004399875	1.749343368
178	00000046268	Ldoc1l	4.661095482	0.172893038	7.43E-05	0.004399875	1.736443778
179	00000036832	Edg7	4.654611525	0.284548408	7.54E-05	0.004441692	3.03246066
180	00000029070	Mxra8	-4.651421842	0.284032477	7.60E-05	0.004443249	0.364405116
181	00000024841	2010003J03Rik	4.650103508	0.102816434	7.63E-05	0.004443249	1.425974046
182	00000030435	n.d.	4.645840978	0.228959766	7.71E-05	0.004468544	2.392982948
183	00000042606	Hirip3	4.640669384	0.17511509	7.83E-05	0.004478626	1.743909864
184	00000045122	Atp6v0c	-4.638554235	0.135699902	7.87E-05	0.004478626	0.655108605
185	00000000247	Lhx2	4.637635883	0.214739316	7.89E-05	0.004478626	2.426177411
186	00000032041	n.d.	-4.637205468	0.104175243	7.90E-05	0.004478626	0.712173162
187	00000054545	Ugt1a6b	4.631772048	0.340897777	8.01E-05	0.004493885	2.97824025
188	00000036503	Rnf13	-4.631425021	0.151074497	8.01E-05	0.004493885	0.62928456
189	00000027274	Mkks	-4.625795597	0.112165028	8.13E-05	0.004519715	0.712489671
190	00000005718	Tcfap4	4.625266729	0.054014905	8.14E-05	0.004519715	1.189286011
191	00000041264	Uspl1	4.620583958	0.127841224	8.24E-05	0.004520523	1.580102952
192	00000033006	Sox10	4.616639382	0.157054361	8.32E-05	0.004520523	1.637665819
193	00000026470	Stx6	4.615864664	0.148063246	8.33E-05	0.004520523	1.603370992
194	00000020225	Tmbim4	-4.61550506	0.116108216	8.34E-05	0.004520523	0.695432256
195	00000040225	Bat2d	4.610173165	0.20198687	8.46E-05	0.004520523	1.968445961
196	00000049775	n.d.	-4.609208164	0.207705614	8.48E-05	0.004520523	0.507623105
197	00000050731	n.d.	4.608072979	0.179973762	8.50E-05	0.004520523	1.784790027
198	00000032591	Mst1	4.60721176	0.17384106	8.52E-05	0.004520523	1.96460711
199	00000031200	Mtcp1	4.604074597	0.099829714	8.59E-05	0.004520523	1.361394673
200	00000040152	Thbs1	-4.601763725	0.226681146	8.63E-05	0.004520523	0.466955988
201	00000039770	Ypel5	-4.601019679	0.162561059	8.65E-05	0.004520523	0.625549975
202	00000031066	Usp11	4.60052531	0.17503956	8.66E-05	0.004520523	1.84687292
203	00000046280	She	-4.596169434	0.073458857	8.77E-05	0.004553015	0.791424541
204	00000030528	Blm	4.592798795	0.123417996	8.84E-05	0.004567218	1.50868178
205	00000061397	BC031593	4.587341628	0.430026871	8.97E-05	0.004611568	3.429396108
206	00000038147	Cd84	-4.584016392	0.067900864	9.05E-05	0.004611859	0.811456436
207	00000050777	Tmem37	-4.58373549	0.268051331	9.05E-05	0.004611859	0.391619019
208	00000017707	Serinc3	-4.579723236	0.232877244	9.14E-05	0.00461747	0.491444755
209	00000019982	Myb	4.578172088	0.417192102	9.19E-05	0.00461747	3.825236221
210	00000025133	2610034N24Rik	4.576994902	0.147759685	9.22E-05	0.00461747	1.605598204
211	00000030987	Stim1	4.575868157	0.203833288	9.24E-05	0.00461747	1.899764766
212	00000025701	Alox5	-4.573290956	0.154741439	9.31E-05	0.00462436	0.616945846
213	00000045609	n.d.	4.572052802	0.157436087	9.34E-05	0.00462436	1.731503548
214	00000015812	Gnrh1	-4.570148389	0.143082605	9.39E-05	0.004627066	0.644382446
215	00000002489	Tiam1	4.558553157	0.204465838	9.67E-05	0.004635479	1.893343976
216	00000032470	Mras	-4.558492958	0.103786348	9.67E-05	0.004635479	0.712849014
217	00000047832	Cdca4	4.558340706	0.098906439	9.68E-05	0.004635479	1.39775979
218	00000040434	n.d.	4.555806652	0.260157178	9.75E-05	0.004635479	2.387522964
219	00000021319	Sfrp4	-4.555547355	0.19511907	9.75E-05	0.004635479	0.54640235
220	00000027248	Pdia3	-4.555482132	0.168744198	9.76E-05	0.004635479	0.596291058
221	00000022421	Cbx6	4.555461937	0.308900968	9.76E-05	0.004635479	2.48333597
222	00000040528	Gm885	-4.553549374	0.214665845	9.80E-05	0.004635479	0.501799554
223	00000045482	Trrap	4.553504723	0.114141683	9.80E-05	0.004635479	1.448242018
224	00000046691	5830457O10Rik	4.55000346	0.172694739	9.90E-05	0.00465966	1.661526541
225	00000034248	Slc25a37	-4.546978808	0.194308425	9.98E-05	0.00466081	0.516194456
226	00000018927	Ccl6	-4.546388784	0.177564857	9.99E-05	0.00466081	0.569592773
227	00000018930	Ccl4	-4.543495655	0.184020159	0.000100645	0.004674922	0.575261224
228	00000028832	Stmn1	4.541328952	0.178351219	0.000101234	0.004681649	1.784832702
229	00000038071	Npy6r	-4.537426332	0.092990382	0.000102243	0.004707683	0.746182215
230	00000034057	Gm239	4.531513959	0.192098644	0.000103897	0.004763055	2.021116604
231	00000038295	Nos3as	-4.528042922	0.172916528	0.0001048	0.004775003	0.55714816
232	00000062519	Zfp398	4.523930687	0.135253007	0.000106028	0.004775003	1.579432854
233	00000025511	Tspan4	-4.523478597	0.247079106	0.000106124	0.004775003	0.430299671
234	00000000409	Lck	4.521444434	0.277899566	0.0001066	0.004775003	2.93071729
235	00000037362	Nov	-4.520903223	0.247477721	0.000106741	0.004775003	0.455999991
236	00000002803	Btbd6	4.520440308	0.126139221	0.000106875	0.004775003	1.527110521
237	00000040522	Tlr8	-4.515719461	0.120012083	0.000108199	0.004795001	0.69154627
238	00000035401	2210018M11Rik	4.515558246	0.114156852	0.000108232	0.004795001	1.460740557
239	00000026048	Ercc5	4.51342314	0.103567396	0.000108799	0.004799926	1.400096376
240	00000031264	Btk	-4.509514001	0.114256819	0.000110004	0.004812409	0.709132742
241	00000016554	Eif3s7	4.507909201	0.093366506	0.000110448	0.004812409	1.325478485
242	00000059714	Flot1	-4.507823901	0.132032583	0.000110464	0.004812409	0.699722619
243	00000026605	Cenpf	4.506153501	0.274226848	0.000110907	0.004812409	2.222233945
244	00000028621	2810410C14Rik	4.49927902	0.129717776	0.000112893	0.004878473	1.551416779
245	00000028195	Cyr61	-4.489778016	0.283329738	0.000115831	0.004985027	0.423248195
246	00000014778	Fhod1	-4.482162251	0.184425505	0.000118029	0.005038743	0.557314152
247	00000030744	Rps3	4.48208475	0.104972825	0.000118035	0.005038743	1.395528874
248	00000038623	Tm6sf1	-4.470719669	0.11804399	0.000121596	0.005169827	0.702615041
249	00000032596	Ube1l	-4.463951248	0.212936811	0.000123856	0.005244766	0.508780277
250	00000029861	6330503C03Rik	-4.460479506	0.07747178	0.000125034	0.005273456	0.800620641
251	00000038781	AW049765	-4.456684089	0.249746874	0.000126228	0.005302624	0.444849606
252	00000067599	Klra11	-4.454653082	0.085293343	0.000126996	0.005313728	0.780760383
253	00000038068	Ibrdc2	4.449442872	0.20778896	0.000128903	0.005372188	2.125581471
254	00000038305	2810022L02Rik	4.447831586	0.395717639	0.000129441	0.005373387	3.507703005
255	00000027287	Snap23	-4.440252182	0.15448575	0.000131786	0.005440659	0.648547314
256	00000029390	Tmed2	-4.439490947	0.138982123	0.000132094	0.005440659	0.650370823
257	00000022463	Srebf2	4.432952132	0.152157065	0.000134416	0.005489689	1.600977664
258	00000032422	Snx14	-4.432432589	0.103254144	0.000134595	0.005489689	0.733814036
259	00000048398	n.d.	4.431448484	0.095048148	0.000134988	0.005489689	1.366670619
260	00000040952	Rps19	4.430159815	0.133375223	0.000135476	0.005489689	1.524799499
261	00000021917	Spcs1	-4.42761742	0.13912005	0.000136294	0.005489689	0.652096307
262	00000036478	Btg1	-4.426217389	0.221064653	0.000136788	0.005489689	0.489443334
263	00000015807	Dock5	-4.425166095	0.151533132	0.00013713	0.005489689	0.660120266
264	00000030457	2810426N06Rik	4.4244255	0.151175904	0.00013745	0.005489689	1.609480729
265	00000028186	Uox	-4.422293017	0.172991267	0.00013819	0.005498427	0.607509761
266	00000002265	Peg3	4.418086944	0.35695285	0.000139609	0.005533996	2.698893026
267	00000048409	1700052K11Rik	4.413582987	0.112870048	0.000141151	0.005541121	1.425382506
268	00000021470	0610007P08Rik	4.412560472	0.114886837	0.000141543	0.005541121	1.467386168
269	00000030469	Zfp719	4.410898291	0.143862717	0.000142255	0.005541121	1.581156178
270	00000024565	Sall3	-4.40899635	0.046924477	0.000142917	0.005541121	0.867250297
271	00000018651	Tada2l	4.407881204	0.208367297	0.000143259	0.005541121	2.11583355
272	00000031107	Rbmx2	4.407240095	0.055182462	0.000143478	0.005541121	1.187280147
273	00000036109	Mbnl3	4.404481252	0.238042415	0.000144409	0.005541121	2.127830699
274	00000022215	1110028A07Rik	-4.401456719	0.163500527	0.000145592	0.005541121	0.604940545
275	00000026688	Mgst3	-4.400260799	0.179991579	0.000146035	0.005541121	0.562034118
276	00000027900	Tmem77	-4.399216032	0.164620941	0.000146456	0.005541121	0.619242608
277	00000030222	Rerg	4.398736419	0.102472176	0.000146652	0.005541121	1.388702462
278	00000018849	Wwc1	4.398285395	0.196582218	0.000146837	0.005541121	2.006147767
279	00000030218	Mgp	4.397746552	0.308293346	0.000147	0.005541121	2.72980289
280	00000020982	Sdccag1	4.397173455	0.122955573	0.000147146	0.005541121	1.495300387
281	00000032013	Trim29	4.390060374	0.432903377	0.000149983	0.005595911	2.950571455
282	00000031078	Cttn	-4.390027176	0.164556848	0.000149994	0.005595911	0.591183292
283	00000050105	Grrp1	4.388263253	0.118559539	0.000150639	0.005595911	1.472947909
284	00000042389	Tsen2	4.388101104	0.190324022	0.000150723	0.005595911	1.824455472
285	00000032540	Abhd5	-4.382774631	0.136613673	0.000152899	0.005615948	0.680953632
286	00000064201	Krt2-17	4.38207075	0.06976777	0.00015323	0.005615948	1.246844065
287	00000028261	1110007M04Rik	4.381141576	0.162367507	0.000153617	0.005615948	1.629113414
288	00000029784	1700025E21Rik	-4.375555743	0.127139289	0.000155956	0.005615948	0.686145135
289	00000032434	Cmtm6	-4.375410196	0.105539656	0.000155995	0.005615948	0.7288462
290	00000026574	Dpt	-4.375324587	0.304270203	0.000156034	0.005615948	0.351344088
291	00000003227	Edar	4.374805605	0.354819225	0.00015623	0.005615948	3.85484531
292	00000003863	2410127E16Rik	-4.374680484	0.077599548	0.000156292	0.005615948	0.796517914
293	00000022967	Ifnar1	-4.374672079	0.126932136	0.000156292	0.005615948	0.674645354
294	00000032570	Atp2c1	-4.373833899	0.13587832	0.000156589	0.005615948	0.668590845
295	00000034377	Tulp4	-4.371679138	0.120455343	0.000157492	0.005629182	0.702443112
296	00000049964	D530005L17Rik	4.369016516	0.173460123	0.000158726	0.005654113	1.761319095
297	00000010048	Ifrd2	4.36747499	0.147562248	0.000159309	0.005655781	1.543211827
298	00000020994	Pnn	4.365576117	0.112568389	0.000160117	0.005665375	1.449168152
299	00000030035	Wbp1	4.359972622	0.119330854	0.000162393	0.005726717	1.442194952
300	00000036537	Rnf113a1	4.358206483	0.12060579	0.000163106	0.00573266	1.480433252
301	00000044674	Fzd1	4.353839765	0.084245278	0.000164956	0.005778441	1.300883157
302	00000031871	Cdh5	-4.349778067	0.112463586	0.000166784	0.005823137	0.725455821
303	00000071060	Gypa	4.34602037	0.161971306	0.000168557	0.005836622	1.679827909
304	00000032313	AI118078	4.345555898	0.145927883	0.000168781	0.005836622	1.645844871
305	00000047669	1700060H10Rik	4.345469173	0.122302534	0.000168831	0.005836622	1.448037725
306	00000058070	n.d.	-4.342316017	0.110940944	0.000170239	0.00586605	0.708809673
307	00000024150	Mcfd2	-4.340722532	0.189931487	0.000171108	0.005873904	0.554132598
308	00000023048	Prr13	-4.338704293	0.085454673	0.000171989	0.005873904	0.77525209
309	00000020941	1700028N14Rik	-4.338095888	0.123839961	0.00017223	0.005873904	0.700003279
310	00000020120	Plek	-4.336864417	0.234996659	0.000172695	0.005873904	0.46725173
311	00000007041	Clic1	-4.329191378	0.180926588	0.00017643	0.005981643	0.587979634
312	00000040557	Wbscr27	4.32671119	0.181520597	0.000177501	0.005984299	1.759709825
313	00000039109	F13a1	-4.326152267	0.100933442	0.00017786	0.005984299	0.755229015
314	00000051451	Zf	4.324919292	0.111315723	0.000178438	0.005984299	1.423403188
315	00000042699	Dhx9	4.324255229	0.075786594	0.000178802	0.005984299	1.256036527
316	00000048266	n.d.	4.323019457	0.107753136	0.000179346	0.005984299	1.390597907
317	00000044030	Irf2bp1	4.321587989	0.154990854	0.000180053	0.005988924	1.577542841
318	00000025795	Rassf3	-4.317536279	0.210676041	0.000182072	0.005995347	0.514393006
319	00000035258	Abi3bp	-4.317155072	0.360968213	0.000182251	0.005995347	0.276924748
320	00000026586	Prrx1	-4.317142325	0.262327803	0.000182262	0.005995347	0.471222264
321	00000032735	Ablim3	-4.316529962	0.081065423	0.00018252	0.005995347	0.797728037
322	00000029868	Trpv6	4.315297083	0.194450859	0.000183109	0.005996009	1.924206427
323	00000035314	Gdpd5	4.309165283	0.210613563	0.000185862	0.00604655	1.844173418
324	00000028354	Fmn2	4.309041715	0.223289094	0.000185913	0.00604655	2.224657496
325	00000044141	E130201H02Rik	4.308183232	0.149821334	0.000186373	0.00604655	1.612234227
326	00000040511	Pvr	-4.304751045	0.091057283	0.000188038	0.006067974	0.762265653
327	00000023885	Thbs2	-4.304320006	0.433549276	0.000188184	0.006067974	0.216286792
328	00000034164	Emid1	4.302838403	0.199218353	0.000188852	0.006070927	1.828068434
329	00000021549	Rasa1	-4.301469463	0.121142191	0.000189524	0.006074042	0.706244248
330	00000005566	Trim28	4.300082406	0.140698136	0.00019022	0.006077854	1.585218609
331	00000020929	Eftud2	4.290727438	0.093111553	0.00019479	0.00619715	1.338878822
332	00000033227	Wnt6	4.28970666	0.253625684	0.00019534	0.00619715	2.438155725
333	00000025779	Ly96	-4.288176556	0.163552099	0.000196074	0.00619715	0.653141348
334	00000041736	Bzrp	-4.287774111	0.263827506	0.000196304	0.00619715	0.43470595
335	00000021981	Cab39l	-4.283692074	0.167095724	0.000198548	0.006249254	0.597822818
336	00000041852	Tcf20	4.282049238	0.088157183	0.000199439	0.006258636	1.304036524
337	00000024603	Dctn4	-4.274271703	0.118976542	0.000203454	0.006347735	0.724680095
338	00000020265	Sumo3	4.274231227	0.152722002	0.000203483	0.006347735	1.574414228
339	00000000631	Myo18a	4.271537504	0.199845972	0.000204997	0.006376105	1.884443747
340	00000040162	C030027K23Rik	-4.26972542	0.15918473	0.000206017	0.00638466	0.64492273
341	00000027501	F730031O20Rik	-4.26880135	0.094526719	0.000206483	0.00638466	0.762201985
342	00000024425	Ndfip1	-4.265827416	0.172621476	0.000207997	0.006412673	0.618749573
343	00000019647	Sema6a	4.263230235	0.093589959	0.000209376	0.006419737	1.337913108
344	00000025577	Cbx2	4.263072445	0.193023095	0.000209444	0.006419737	1.854460764
345	00000036928	Stag3	4.257039383	0.350006181	0.000212808	0.006490714	3.875800264
346	00000027581	Stmn3	-4.256127988	0.12028019	0.00021333	0.006490714	0.710904596
347	00000035751	Tubgcp6	4.254891934	0.0524418	0.000214171	0.006490714	1.172209786
348	00000062190	Lancl2	4.254784843	0.127375302	0.000214222	0.006490714	1.503060054
349	00000020961	Ston2	4.252897843	0.148850714	0.000215293	0.006504477	1.653646626
350	00000050323	n.d.	4.250141876	0.177384419	0.000216818	0.006506995	1.692639226
351	00000024158	Hagh	-4.249569265	0.142085422	0.000217093	0.006506995	0.67764053
352	00000040586	Ofd1	4.249307151	0.112760338	0.000217227	0.006506995	1.431184133
353	00000049718	n.d.	-4.247593811	0.143137563	0.000218186	0.006512566	0.667851611
354	00000021998	Lcp1	-4.245025344	0.268365012	0.000219701	0.006512566	0.421906146
355	00000037509	Arhgef4	4.243357807	0.155299288	0.000220777	0.006512566	1.690996882
356	00000019775	Rgs17	-4.243096245	0.262393451	0.000220929	0.006512566	0.415752455
357	00000030726	Pold3	4.243017594	0.117784014	0.000220957	0.006512566	1.428870073
358	00000042363	1110067D22Rik	4.242796921	0.137891787	0.000221119	0.006512566	1.555281748
359	00000037892	Pcdh18	4.236992532	0.092796014	0.000224434	0.006571582	1.339980607
360	00000019362	D8Ertd738e	-4.236716435	0.143090631	0.000224607	0.006571582	0.658704857
361	00000044811	Cd300d	-4.234960619	0.097050617	0.000225639	0.006571582	0.756173445
362	00000044694	2010007H06Rik	4.234867323	0.258765356	0.00022569	0.006571582	2.448760351
363	00000033055	C730048E16Rik	4.234081596	0.086980012	0.000226239	0.006571582	1.301129294
364	00000052410	n.d.	4.2323705	0.086223814	0.000227176	0.006575587	1.305095508
365	00000032475	Nck1	-4.231675384	0.103199549	0.000227624	0.006575587	0.751933169
366	00000031314	Taf1	4.229654552	0.114649436	0.000228897	0.006594295	1.41973533
367	00000007564	Ppp2r1a	4.2251476	0.070878768	0.000231544	0.006645384	1.237920386
368	00000031388	Ard1	4.224518305	0.115021327	0.000231931	0.006645384	1.406287868
369	00000045946	n.d.	4.219592319	0.099537461	0.000235055	0.006712458	1.378032867
370	00000020467	Efemp1	-4.218810563	0.266885751	0.000235588	0.006712458	0.433654302
371	00000031155	Pim2	4.217909349	0.121769042	0.000236182	0.006712458	1.480527459
372	00000024660	Incenp	4.21638194	0.113110961	0.000237085	0.006717331	1.398325784
373	00000003161	Sri	-4.214093672	0.117006728	0.000238386	0.006717331	0.72763349
374	00000002524	2410104I19Rik	4.213732269	0.089901479	0.00023865	0.006717331	1.29506513
375	00000009687	Fxyd5	-4.211956056	0.303297063	0.000239754	0.006717331	0.366876689
376	00000002265	Peg3	4.210449843	0.366305162	0.000240741	0.006717331	2.609291627
377	00000036381	P2ry14	-4.209496177	0.064198595	0.000241313	0.006717331	0.839293923
378	00000035448	Ccr3	4.209044956	0.176323331	0.000241611	0.006717331	1.64034938
379	00000006576	Slc4a3	4.208906226	0.139628469	0.000241712	0.006717331	1.518727994
380	00000022360	Atad2	4.208407586	0.149283019	0.000242087	0.006717331	1.581538923
381	00000035373	Ccl7	-4.205520042	0.38464444	0.000243899	0.006749829	0.255817193
382	00000005225	Plekha8	4.202906523	0.219497466	0.000245704	0.006777227	2.038345141
383	00000031950	Gabarapl2	-4.201248649	0.143478141	0.000246635	0.006777227	0.642351096
384	00000070898	n.d.	4.200190479	0.091025653	0.000247359	0.006777227	1.31036069
385	00000045794	4930526D03Rik	-4.200074006	0.18871102	0.00024746	0.006777227	0.61343226
386	00000030967	Zranb1	4.197279939	0.105272811	0.000249103	0.006804553	1.381903125
387	00000031555	n.d.	-4.19557501	0.22063886	0.000250045	0.006812639	0.504405801
388	00000043632	BC035954	4.193414152	0.186899111	0.00025138	0.006827471	1.7493142
389	00000041361	n.d.	-4.192486245	0.15404897	0.000251884	0.006827471	0.631321122
390	00000028582	Cc2d1b	4.183400439	0.138027443	0.000258053	0.00696525	1.586783243
391	00000041355	Ssr2	-4.183075925	0.1243524	0.000258288	0.00696525	0.704987622
392	00000031373	Car5b	-4.180500499	0.097857766	0.00026015	0.006977348	0.754257785
393	00000019982	Myb	4.179660388	0.451501418	0.000260666	0.006977348	3.818047798
394	00000003541	Ier3	-4.179553269	0.271851048	0.000260756	0.006977348	0.477564959
395	00000026872	Zfhx1b	-4.178459248	0.154126988	0.000261384	0.006977348	0.663380379
396	00000009575	Cbx5	4.174740693	0.148221441	0.000263874	0.007004922	1.610872366
397	00000051124	Gimap9	4.173492334	0.11181451	0.000264766	0.007004922	1.385584633
398	00000027932	Slc27a3	4.172285764	0.101360007	0.000265545	0.007004922	1.347745134
399	00000048047	Zbtb33	4.171366225	0.111510335	0.000266162	0.007004922	1.436757064
400	00000047386	n.d.	4.171148267	0.075898026	0.000266285	0.007004922	1.268854181
401	00000023073	Slc10a2	4.17089491	0.094291533	0.000266403	0.007004922	1.339934729
402	00000000555	Itga5	-4.167184364	0.210778015	0.000268882	0.007052511	0.515372854
403	00000032271	Nnmt	-4.162050853	0.077629791	0.000272611	0.007104014	0.805098295
404	00000032089	Il10ra	-4.161249291	0.150190464	0.000273133	0.007104014	0.640311993
405	00000054203	Ifi205	-4.161109284	0.362061877	0.00027325	0.007104014	0.344604123
406	00000040794	C1qtnf4	4.160684768	0.135569983	0.000273637	0.007104014	1.505651115
407	00000020850	Prpf8	4.159101766	0.125272548	0.00027477	0.007104014	1.467792178
408	00000031922	Cep57	4.15895277	0.111413641	0.000274888	0.007104014	1.419602414
409	00000047952	n.d.	4.153010886	0.168772404	0.00027897	0.007191893	1.667664819
410	00000047261	Gap43	-4.151559266	0.239473831	0.000280086	0.007194014	0.512080701
411	00000049620	Prss33	4.151136703	0.174251712	0.000280417	0.007194014	1.790632663
412	00000038079	n.d.	4.14748282	0.191274562	0.000283115	0.007245586	1.864607742
413	00000015013	1810017G16Rik	-4.142650127	0.153917548	0.000286586	0.007316666	0.63507463
414	00000001930	Vwf	-4.140161061	0.119957195	0.000288425	0.007345839	0.717279354
415	00000030560	Ctsc	-4.138255511	0.256128188	0.000289833	0.007363902	0.474008818
416	00000026283	Ing5	4.136758842	0.084393452	0.0002911	0.007367112	1.295402778
417	00000034560	A230046K03Rik	-4.135053584	0.133586894	0.000292452	0.007367112	0.703716369
418	00000026179	Pnkd	4.134280794	0.240162727	0.00029299	0.007367112	1.871723099
419	00000032883	Utp14b	4.134077307	0.127623573	0.000293114	0.007367112	1.437800606
420	00000026308	4631423F02Rik	-4.133581939	0.096677793	0.000293472	0.007367112	0.771126545
421	00000034023	Fancd2	4.130764364	0.127181058	0.000295626	0.007367112	1.516093103
422	00000030515	Tarsl2	4.130671151	0.109125696	0.000295744	0.007367112	1.361745647
423	00000000958	Slc7a7	-4.127909328	0.117041277	0.000297734	0.007367112	0.719147246
424	00000026240	Cops7b	4.126422611	0.075150542	0.000298912	0.007367112	1.243738519
425	00000035359	Ccr5	-4.125775701	0.210039054	0.000299467	0.007367112	0.517904934
426	00000027349	2610510H03Rik	4.125734339	0.350202733	0.000299529	0.007367112	2.808134911
427	00000044121	5430402E10Rik	4.125642601	0.083239754	0.000299585	0.007367112	1.290040371
428	00000031758	Cdyl2	-4.124354359	0.075451492	0.000300572	0.007367112	0.812118428
429	00000031903	Lypla3	-4.123806874	0.173338822	0.000301082	0.007367112	0.588145519
430	00000024853	Sf3b2	4.123719547	0.096650129	0.000301116	0.007367112	1.334209557
431	00000025340	Rabgef1	-4.123674984	0.117430657	0.000301138	0.007367112	0.720600287
432	00000021458	2010111I01Rik	4.122753861	0.110690588	0.000301935	0.007369495	1.412831222
433	00000028194	Ddah1	-4.117376256	0.188205886	0.000306141	0.007452432	0.593367656
434	00000045658	5033414K04Rik	-4.116493652	0.129951166	0.000306746	0.007452432	0.688135962
435	00000041075	Fzd7	4.11229022	0.094622353	0.000310044	0.007515227	1.340889043
436	00000066842	n.d.	4.107369195	0.294601239	0.000314059	0.007595094	2.385670486
437	00000029439	Sfrs8	4.105081683	0.130317334	0.000315893	0.00762196	1.459157366
438	00000028076	Cd1d1	-4.099455349	0.244150595	0.000320699	0.007702694	0.505224291
439	00000026670	Uap1	-4.09740121	0.055326076	0.000322319	0.007702694	0.85789597
440	00000040264	Gbp5	4.097381013	0.07409328	0.000322336	0.007702694	1.25081384
441	00000026718	Stam	-4.097050772	0.106291722	0.000322639	0.007702694	0.743138911
442	00000038608	Dock10	-4.096726333	0.064699231	0.000322891	0.007702694	0.838292224
443	00000050069	Grem2	-4.095233177	0.185332306	0.000324063	0.007713203	0.570403772
444	00000020467	Efemp1	-4.094128418	0.307972637	0.000325034	0.007718871	0.383570143
445	00000036438	Calm1	-4.086773044	0.122555067	0.000330961	0.007830889	0.705424522
446	00000026516	Nvl	4.086493899	0.096865912	0.000331236	0.007830889	1.307462607
447	00000050493	BC030183	-4.085335642	0.09181903	0.000332257	0.007834338	0.787772751
448	00000031818	Cox4i1	-4.084544148	0.123202897	0.000332868	0.007834338	0.697096599
449	00000022510	Trp63	4.082161938	0.4339581	0.00033492	0.007853244	2.520348937
450	00000030649	3200002M19Rik	4.07954982	0.089521002	0.000337349	0.007853244	1.298831686
451	00000030521	Mphosph10	4.078970816	0.110266071	0.000337831	0.007853244	1.379128938
452	00000000159	Jam4	-4.078721335	0.230619704	0.000337993	0.007853244	0.512625101
453	00000003824	Syce2	4.077221215	0.201395989	0.000339278	0.007853244	1.836955311
454	00000037533	Rapgef6	4.07528513	0.215853125	0.000341033	0.007853244	1.937522986
455	00000041040	Als2cr13	4.074728012	0.128470459	0.000341521	0.007853244	1.498461819
456	00000027498	Cstf1	4.074544672	0.106371496	0.000341661	0.007853244	1.377202497
457	00000027322	Siglec1	4.074310131	0.129559014	0.000341863	0.007853244	1.499910722
458	00000022488	Nckap1l	-4.073544787	0.132026473	0.000342541	0.007853244	0.682787952
459	00000051074	4930579K19Rik	4.073523688	0.121612011	0.000342541	0.007853244	1.416233188
460	00000024224	Gm749	-4.073393428	0.085441815	0.000342609	0.007853244	0.791894836
461	00000019734	Tmc4	-4.06808985	0.396602081	0.000347308	0.007943695	0.340337788
462	00000009216	C630035N08Rik	-4.062693489	0.191050411	0.00035212	0.008028662	0.550132944
463	00000026797	Stxbp1	-4.062103055	0.222489486	0.000352546	0.008028662	0.510399587
464	00000015575	Atp6v0e	-4.05913529	0.159700692	0.000355389	0.008075969	0.657602261
465	00000022901	Cd86	-4.053259346	0.141077137	0.000360829	0.008181948	0.656777821
466	00000025983	4930511H11Rik	4.048504034	0.156867331	0.000365354	0.008266789	1.600425896
467	00000038910	Plcl2	-4.043936024	0.054518341	0.000369566	0.008330138	0.864277255
468	00000017386	Traf4	4.043795027	0.104951203	0.000369734	0.008330138	1.373451154
469	00000050867	n.d.	-4.040457505	0.117172106	0.000372948	0.008339937	0.724659073
470	00000008976	Gabpa	4.04026893	0.125516082	0.000373138	0.008339937	1.485608478
471	00000031644	Nek1	4.03928411	0.129146827	0.000374103	0.008339937	1.478137067
472	00000037370	Enpp1	4.038554547	0.138434028	0.000374742	0.008339937	1.51974315
473	00000025535	4930579G22Rik	4.03817453	0.119191656	0.000375129	0.008339937	1.456750024
474	00000018654	Zfpn1a1	-4.037780406	0.10224667	0.000375499	0.008339937	0.751112303
475	00000032564	Cpne4	4.037280819	0.096678219	0.000375965	0.008339937	1.338568685
476	00000020919	Stat5b	-4.03622861	0.149018135	0.000377086	0.008339937	0.653801018
477	00000070544	Top1	4.035451627	0.089515301	0.000377961	0.008339937	1.30334305
478	00000020692	Nle1	4.035278496	0.146161533	0.000378079	0.008339937	1.581445241
479	00000011486	4933406J04Rik	-4.032569563	0.124913391	0.000380995	0.008386717	0.721556605
480	00000029186	Pi4k2b	-4.029578311	0.170448361	0.000383883	0.008432686	0.60742778
481	00000028191	Bcl10	-4.026553199	0.147116266	0.000386664	0.008476129	0.67389575
482	00000047207	Olfr1495	4.018499941	0.158246885	0.000394858	0.008637774	1.63117967
483	00000048962	n.d.	4.013284803	0.143420994	0.000400578	0.008728893	1.481151164
484	00000022385	Gtse1	4.013173413	0.130611275	0.000400679	0.008728893	1.449702389
485	00000057133	Chd6	4.01114403	0.112573742	0.00040286	0.008743874	1.377752241
486	00000041147	Brca2	4.009708528	0.221491164	0.000404352	0.008743874	1.927898724
487	00000031838	Ifi30	-4.009566011	0.141989135	0.000404498	0.008743874	0.665211791
488	00000017548	Suz12	4.009104467	0.132353616	0.000404963	0.008743874	1.500449082
489	00000037892	Pcdh18	4.008558046	0.209637757	0.000405513	0.008743874	1.936202603
490	00000049484	n.d.	4.006254935	0.097321977	0.000407896	0.008770124	1.326313852
491	00000024742	Fen1	4.005360408	0.129818855	0.00040886	0.008770124	1.475652694
492	00000022061	Nkx3-1	4.004390329	0.165831179	0.000409876	0.008770124	1.751890412
493	00000021464	Ror2	4.004139878	0.12897272	0.000410094	0.008770124	1.466262632
494	00000031381	Piga	4.003147386	0.172312723	0.00041112	0.008770124	1.709603032
495	00000023336	Wfdc1	-4.00254325	0.117006599	0.000411721	0.008770124	0.724731808
496	00000024381	Bin1	-4.000059577	0.275903497	0.000414295	0.0088011	0.46912883
497	00000030533	Unc45a	3.999584119	0.197185419	0.000414844	0.0088011	1.846299092
498	00000045092	Edg1	-3.996730176	0.16926613	0.000417985	0.008832894	0.608780522
499	00000029867	1700034O15Rik	-3.996689088	0.093850017	0.000418018	0.008832894	0.772374116
500	00000035390	Brsk1	-3.994743561	0.087934833	0.000420216	0.008861586	0.798959922
501	00000017405	Nek8	3.993150541	0.099851408	0.000421927	0.008879896	1.32478253
502	00000031158	Timm17b	3.991836027	0.111261262	0.000423323	0.008891493	1.404480818
503	00000037922	Bank1	-3.991060321	0.152154848	0.000424164	0.008891493	0.656312504
504	00000002332	Dhrs1	-3.990251764	0.061216684	0.000425084	0.008893091	0.844261905
505	00000046865	Fbl	3.987893597	0.135292152	0.000427697	0.008930045	1.495108652
506	00000037475	n.d.	3.986904437	0.109571913	0.000428841	0.008936236	1.377652615
507	00000026620	Mark1	3.984585281	0.241270845	0.00043118	0.008939095	1.860541479
508	00000002228	Ppm1j	-3.984411329	0.090401908	0.00043141	0.008939095	0.781434739
509	00000026172	Bcs1l	3.984303299	0.138367211	0.000431522	0.008939095	1.470709535
510	00000021969	Zdhhc20	-3.983158954	0.150110015	0.000432716	0.008946263	0.678093645
511	00000024232	Bambi	3.981068918	0.102362647	0.000434892	0.008973653	1.335852637
512	00000028948	Nol9	3.97846718	0.153024581	0.000438038	0.009020915	1.533268518
513	00000024483	Ankhd1	3.975597172	0.16166778	0.000441257	0.009054838	1.595086153
514	00000030780	BC017158	3.975488844	0.057535689	0.000441403	0.009054838	1.175891261
515	00000008999	Bmp7	3.97374786	0.658433758	0.000443568	0.009081574	2.825759425
516	00000021591	Glrx	-3.972918241	0.314898176	0.000444583	0.00908183	0.374225892
517	00000028582	Cc2d1b	3.972159257	0.126476802	0.000445424	0.00908183	1.442053474
518	00000030714	1700023O11Rik	3.971514645	0.137215818	0.000446164	0.00908183	1.480802989
519	00000015468	Notch4	-3.962709833	0.145202666	0.000456449	0.00927328	0.695278724
520	00000045733	Sprn	-3.958945641	0.084855116	0.00046102	0.009348122	0.806737143
521	00000032892	2400006H24Rik	3.95806077	0.265489532	0.000461917	0.009348339	2.032065329
522	00000001100	Poldip2	3.956659254	0.103156565	0.000463459	0.009361581	1.365969467
523	00000006014	Prg4	-3.951828846	0.36666675	0.000469056	0.009439145	0.414438157
524	00000028677	4931406I20Rik	3.951784681	0.082424011	0.000469089	0.009439145	1.256124573
525	00000050978	n.d.	3.948080934	0.129022207	0.000473604	0.009511831	1.429121644
526	00000004100	Ppan	3.946969539	0.107970349	0.00047509	0.009523538	1.375239891
527	00000019945	1700040L02Rik	3.946007072	0.330121099	0.000476436	0.009532395	3.918553114
528	00000013539	D16H22S680E	-3.944323065	0.108677768	0.000478202	0.009533217	0.74139043
529	00000031377	Bmx	3.943707698	0.089273678	0.000478987	0.009533217	1.298607676
530	00000037674	Rfxdc2	3.943517984	0.164302964	0.000479189	0.009533217	1.626955688
531	00000022500	Litaf	-3.942266394	0.192772245	0.000480748	0.009546221	0.574699365
532	00000000204	Slfn2	-3.937219602	0.243997122	0.000487214	0.009650115	0.487435911
533	00000026604	Ptpn14	3.935777862	0.152146564	0.000489138	0.009650115	1.597732895
534	00000024381	Bin1	-3.935158097	0.244055745	0.000489973	0.009650115	0.516793758
535	00000049583	Grm5	3.93472115	0.160835263	0.000490545	0.009650115	1.631709598
536	00000035745	Grin3b	3.934715377	0.145083335	0.000490556	0.009650115	1.467130734
537	00000021929	Kpna3	-3.93307273	0.085960215	0.000492766	0.009675529	0.796307826
538	00000025085	Ablim1	3.93204322	0.31090371	0.000494039	0.009677584	3.596497543
539	00000050191	n.d.	-3.931585712	0.099173207	0.000494706	0.009677584	0.767580068
540	00000034850	Tmem127	-3.929535999	0.102039875	0.000497342	0.009711128	0.752111011
541	00000038644	Pold1	3.926078997	0.112175666	0.000501912	0.009782255	1.365105507
542	00000026024	Als2	3.921756285	0.168862695	0.000507425	0.009856535	1.664542099
543	00000042787	Endogl1	3.92155751	0.107224959	0.000507593	0.009856535	1.357656133
544	00000026343	Gpr39	-3.919107327	0.16859285	0.000510896	0.009902438	0.629147877
545	00000022089	Bin3	-3.916495049	0.15875638	0.000514289	0.009949908	0.645096055
546	00000030428	Ttyh1	3.91392834	0.382904047	0.000517856	0.010000562	2.466807598
547	00000021811	Dnajc9	3.912671656	0.131264494	0.0005196	0.010015898	1.441021195
548	00000048227	n.d.	3.909555096	0.120221987	0.000523542	0.010061555	1.393388912
549	00000031148	Gpkow	3.908785259	0.094433831	0.000524624	0.010061555	1.313602682
550	00000020377	Ltc4s	-3.908080656	0.12726295	0.000525527	0.010061555	0.708792214
551	00000039901	9130011E15Rik	3.907868557	0.109012371	0.000525785	0.010061555	1.382605063
552	00000038811	Gngt2	-3.906150384	0.100885297	0.000527899	0.010079755	0.761166607
553	00000029398	Mphosph9	3.904986934	0.226305787	0.000529419	0.010079755	1.996928999
554	00000003135	D1Bwg0212e	3.904863831	0.169200801	0.000529604	0.010079755	1.63743951
555	00000040728	Rbm35a	3.904245965	0.214321665	0.000530563	0.010079812	1.821516631
556	00000050107	Gsg2	3.902107117	0.107333596	0.000533675	0.010120706	1.353371992
557	00000048930	Tada3l	3.892431949	0.078798991	0.000547432	0.010252502	1.251212125
558	00000046679	C87436	3.890002174	0.069735614	0.000550937	0.010299849	1.221195582
559	00000067653	Ankrd39	3.888117072	0.115297916	0.000553712	0.010333424	1.404607337
560	00000022676	Snai2	3.879730887	0.424016761	0.000566246	0.010474632	2.494661687
561	00000032897	Nfyc	3.878139614	0.081675059	0.000568652	0.010496205	1.256830762
562	00000005917	Otx1	3.877228735	0.264619663	0.000569936	0.010496205	2.366938197
563	00000039323	Igfbp2	3.874859457	0.422621463	0.000573385	0.010514457	2.730181838
564	00000052763	Zfp212	3.873898062	0.091389644	0.000574888	0.010523714	1.303075907
565	00000025050	Pcgf6	3.869923569	0.156355876	0.00058067	0.010592773	1.614036868
566	00000020594	Pum2	3.863569704	0.172079793	0.000590237	0.010700615	1.620986142
567	00000033295	Ptprf	3.862957445	0.160734905	0.00059124	0.010700615	1.562160269
568	00000014232	Cluap1	3.862604113	0.128480659	0.000591655	0.010700615	1.460593694
569	00000044716	A930013K19Rik	3.860250172	0.070263035	0.000595469	0.010751142	1.218469956
570	00000041815	Poldip3	3.859101269	0.127830356	0.000597202	0.010763997	1.462045424
571	00000071262	n.d.	3.85690335	0.099736051	0.000600684	0.01080829	1.307814666
572	00000030424	n.d.	3.855153051	0.12856711	0.000603269	0.010836315	1.448676039
573	00000029726	Bcdin3	3.850337296	0.180195929	0.000610846	0.010953744	1.719502935
574	00000030141	V2r1b	3.849219683	0.089962514	0.000612635	0.010967172	1.301000885
575	00000020258	6230410P16Rik	3.847611391	0.107527735	0.000615085	0.010992379	1.382296078
576	00000066248	n.d.	3.845614625	0.181470791	0.000618299	0.011009958	1.785887383
577	00000048031	Fcrl5	3.841976623	0.079552023	0.000624327	0.011045773	1.257430731
578	00000041415	Dicer1	3.84085103	0.108032456	0.000626037	0.011045773	1.373609556
579	00000022466	D15Ertd682e	3.839962247	0.152214327	0.000627501	0.011045773	1.537459575
580	00000034227	Foxj1	3.837778084	0.126906142	0.000631034	0.01108945	1.437361248
581	00000037275	Gemin5	3.834422985	0.125814962	0.000636474	0.011166432	1.455736349
582	00000020840	Blmh	3.831499702	0.095939786	0.000641319	0.011206029	1.305073323
583	00000047921	n.d.	3.831237732	0.085667569	0.000641756	0.011206029	1.278513257
584	00000049761	4930479M11Rik	3.82703835	0.045095999	0.000648744	0.011275918	1.129839414
585	00000026470	Stx6	3.826780545	0.122992936	0.000649131	0.011275918	1.456119104
586	00000018395	Kif3a	3.825371097	0.092944885	0.000651576	0.011282305	1.312170923
587	00000047193	Dync2h1	3.823901595	0.130310622	0.000654032	0.011282305	1.467864487
588	00000022565	Plec1	3.823087494	0.307773877	0.000655479	0.011282305	2.235073409
589	00000016427	Ndufa1	3.822967391	0.112879955	0.000655686	0.011282305	1.368227044
590	00000037280	Galnt6	3.821586359	0.229730171	0.00065798	0.011282305	2.177960739
591	00000046848	n.d.	3.819436272	0.090733889	0.000661833	0.011325276	1.286796588
592	00000031171	Ftsj1	3.818063542	0.123309257	0.000664295	0.011333932	1.432289612
593	00000001120	Pcbp3	3.814143706	0.141892871	0.000671147	0.011432354	1.555444538
594	00000032940	Rbm11	3.813382707	0.136119592	0.000672437	0.011433777	1.518152952
595	00000036305	Rpl39	3.81220839	0.135059215	0.000674484	0.011433777	1.483793963
596	00000034168	6430527G18Rik	3.808982694	0.104013598	0.000680154	0.011474544	1.340027215
597	00000038600	Atp6v0a4	3.80622452	0.258619182	0.000685223	0.011541603	2.361773348
598	00000001632	Brpf1	3.79930458	0.103766204	0.000697594	0.011712555	1.333614401
599	00000025474	Tubgcp2	3.795064058	0.106996314	0.000705501	0.011778952	1.366132466
600	00000038740	2610528K11Rik	3.785655632	0.240970541	0.000722538	0.011978766	2.321083211
601	00000016262	Sertad4	3.779375478	0.182288489	0.000734522	0.012101337	1.637787441
602	00000022557	Bop1	3.778331872	0.119983188	0.000736603	0.012104191	1.40977475
603	00000046394	n.d.	3.778009873	0.060012777	0.00073718	0.012104191	1.17071927
604	00000022201	Zfr	3.775661661	0.108711809	0.000741538	0.012112616	1.337978496
605	00000019996	Mtap7	3.774792621	0.210234304	0.000743248	0.012112616	1.827611151
606	00000051517	E130306D19Rik	3.772843736	0.125436737	0.000747179	0.01214107	1.401407038
607	00000025384	2310003H01Rik	3.765846261	0.116954786	0.000761294	0.01231175	1.38505901
608	00000003031	Cdkn1b	3.763716125	0.333843081	0.00076531	0.012338655	2.513069878
609	00000040482	Dom3z	3.762396742	0.081926977	0.00076776	0.012359267	1.262873945
610	00000049092	Gm908	3.758018831	0.128930293	0.000776447	0.012459909	1.4530916
611	00000020807	4933427D14Rik	3.755829371	0.181299439	0.000780972	0.012495645	1.790044275
612	00000021037	Ahsa1	3.754121766	0.099105496	0.000784578	0.012498417	1.313550997
613	00000030556	Lrrc28	3.754033426	0.145079545	0.000784702	0.012498417	1.577533836
614	00000036980	Taf6	3.751334743	0.091164965	0.000790153	0.012511445	1.276048576
615	00000031028	Tub	3.750704923	0.07308528	0.000791543	0.012511445	1.223264125
616	00000035202	Lars2	3.75007031	0.253122265	0.000792985	0.012511445	1.91608471
617	00000026131	Dst	3.749605017	0.233581453	0.000793826	0.012511445	1.868484016
618	00000027570	Col9a3	3.748622606	0.225030485	0.000795917	0.012525689	1.866094127
619	00000047109	Cldn14	3.74687293	0.136214605	0.00079963	0.012565359	1.50185443
620	00000024795	Mphosph1	3.743592448	0.147439601	0.000806718	0.012657882	1.524537327
621	00000041530	Eif2c1	3.741394652	0.095101043	0.000811547	0.012673865	1.280849482
622	00000031644	Nek1	3.741117796	0.241868154	0.000812197	0.012673865	2.056615048
623	00000039187	BC025462	3.738125879	0.136067291	0.000818343	0.012707913	1.460798158
624	00000014907	BC053440	3.731969057	0.220920455	0.000831673	0.0128301	1.979037605
625	00000041789	2700046A07Rik	3.731662867	0.150432147	0.000832296	0.0128301	1.557872178
626	00000010554	n.d.	3.730990358	0.135310267	0.000833816	0.012834763	1.475500647
627	00000020961	Ston2	3.729911299	0.306633997	0.000836233	0.012842622	2.560347167
628	00000043162	Pigy	3.729385975	0.121259208	0.000837421	0.012842622	1.389563265
629	00000054545	Ugt1a2	3.728410001	0.241460283	0.000839698	0.012842622	1.940957906
630	00000058825	Olfr456	3.728063894	0.150473009	0.000840416	0.012842622	1.534661902
631	00000027378	Nphp1	3.726472331	0.078749888	0.000843893	0.012877091	1.236783227
632	00000031154	Otud5	3.725425449	0.102046151	0.000846192	0.012893516	1.316277898
633	00000033161	Atp1a1	3.723949173	0.295320357	0.000849523	0.012898777	2.070387818
634	00000040414	Slc25a28	3.723599489	0.086176177	0.000850207	0.012898777	1.256274404
635	00000019326	Psme3	3.722077841	0.09585948	0.000853735	0.012915126	1.291597957
636	00000028540	Dph2	3.7215336	0.058254394	0.000854985	0.012915514	1.17252472
637	00000025815	Dhtkd1	3.720712196	0.070934085	0.000856948	0.012926644	1.214104192
638	00000031491	Chrna6	3.718695025	0.100865049	0.000861457	0.012939124	1.310229544
639	00000044025	Olfr790	3.715340139	0.121241489	0.000868753	0.012993182	1.364069528
640	00000035047	BC021438	3.712095652	0.096767155	0.000875886	0.013029464	1.297052313
641	00000027793	Ccna1	3.712017156	0.094849034	0.000876122	0.013029464	1.296948396
642	00000048122	n.d.	3.710213987	0.114939844	0.000880361	0.013074074	1.386756758
643	00000025529	n.d.	3.704779347	0.250771308	0.000893377	0.013204969	2.008396403
644	00000047649	Cd3eap	3.70443034	0.103990826	0.000894185	0.013204969	1.32234164
645	00000022000	3110050K21Rik	3.703581008	0.168887083	0.000896119	0.013207972	1.575509771
646	00000001089	Luzp1	3.703239951	0.202054827	0.000896893	0.013207972	1.624928813

values represent the relative difference between gene expression levels in tumors from K14cre;p53^F/F and K14cre;Brca1^F/F;p53^F/F mice. Positive D values indicate upregulation in Brca1^{Δ/Δ};p53^{Δ/Δ} tumors; negative values indicate down-regulation in Brca1^{Δ/Δ};p53^{Δ/Δ} tumors.

Table 5. Selected GO classes overrepresented in the BRCA1 reporter gene set

Biological process	ENSMUSG ID	Symbol	Name
Cell cycle	00000028191	Bcl10	B cell leukemia/lymphoma 10
	00000024381	Bin1	bridging integrator 1
	00000022089	Bin3	bridging integrator 3
	00000041147	Brca2	breast cancer 2
	00000035390	Brsk1	BR serine/threonine kinase 1
	00000036438	Calm2	calmodulin 2
	00000027793	Ccna1	cyclin A1
	00000024791	Cdca5	cell division cycle associated 5
	00000003031	Cdkn1b	cyclin-dependent kinase inhibitor 1B
	00000022770	Dlgh1	discs, large homolog 1 (Drosophila)
	00000026131	Dst	dystonin
	00000034023	Fancd2	Fanconi anemia, complementation group D2
	00000050107	Gsg2	germ cell-specific gene 2
	00000024660	Incenp	inner centromere protein
	00000032968	Inha	inhibin alpha
	00000025809	Itgb1	integrin beta 1 (fibronectin receptor beta)
	00000000409	Lck	lymphocyte protein tyrosine kinase
	00000023186	Loh11cr2a	loss of heterozygosity, 11, chromosomal region 2, gene A homolog
	00000019982	Myb	myeloblastosis oncogene
	00000017861	Mybl2	myeloblastosis oncogene-like 2
	00000000441	Raf1	v-raf-leukemia viral oncogene 1
	00000036928	Stag3	stromal antigen 3
	00000020919	Stat5b	signal transducer and activator of transcription 5B
	00000028832	Stmn1	stathmin 1
	00000003824	Syce2	synaptonemal complex central element protein 2
	00000035235	Trim13	tripartite motif protein 13
	00000032883	Utp14b	UTP14, U3 small nucleolar ribonucleoprotein, homolog B
	00000016458	Wt1	Wilms tumor homolog
Cell differentiation	00000025085	Ablim1	actin-binding LIM protein 1
	00000000861	Bcl11a	B cell CLL/lymphoma 11A (zinc finger protein)
	00000024381	Bin1	bridging integrator 1
	00000008999	Bmp7	bone morphogenetic protein 7
	00000035390	Brsk1	BR serine/threonine kinase 1
	00000036478	Btg1	B cell translocation gene 1, anti-proliferative
	00000027793	Ccna1	cyclin A1
	00000028076	Cd1d1	CD1d1 antigen
	00000003227	Edar	ectodysplasin-A receptor
	00000044674	Fzd1	frizzled homolog 1 (Drosophila)
	00000047261	Gap43	growth associated protein 43
	00000025001	Hells	helicase, lymphoid specific
	00000010048	Ifrd2	interferon-related developmental regulator 2
	00000032968	Inha	inhibin alpha
	00000025809	Itgb1	integrin beta 1 (fibronectin receptor-b)
	00000000409	Lck	lymphocyte protein tyrosine kinase
	00000036109	Mbnl3	muscleblind-like 3 (Drosophila)
	00000030218	Mgp	matrix Gla protein
	00000027274	Mkks	McKusick-Kaufman syndrome protein
	00000020692	Nle1	notchless homolog 1 (Drosophila)
	00000015468	Notch4	Notch gene homolog 4 (Drosophila)
	00000005893	Nr2c2	nuclear receptor subfamily 2, group C, member 2
	00000068206	Pick1	protein interacting with C kinase 1
	00000021549	Rasa1	RAS p21 protein activator 1
	00000021464	Ror2	receptor tyrosine kinase-like orphan receptor 2
	00000040952	Rps19	ribosomal protein S19
	00000019647	Sema6a	Semaphorin 6A
	00000021319	Sfrp4	secreted frizzled-related sequence protein 4
	00000020919	Stat5b	signal transducer and activator of transcription 5B
	00000028832	Stmn1	stathmin 1
	00000026797	Stxbp1	syntaxin binding protein 1
	00000002489	Tiam1	T cell lymphoma invasion and metastasis 1
	00000032041	Tirap	toll-interleukin 1 receptor (TIR) domain-containing adaptor protein
	00000039005	Tlr4	toll-like receptor 4
	00000022510	Trp63	transformation related protein 63
	00000032883	Utp14b	UTP14, U3 small nucleolar ribonucleoprotein, homolog B (yeast)
	00000016458	Wt1	Wilms tumor homolog
	00000027803	Wwtr1	WW domain containing transcription regulator 1
	00000018965	Ywhah	tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, b-polypeptide
	00000026872	Zfhx1b	zinc finger homeobox 1b
Chromatin modification	00000040363	Bcor	Bcl6 interacting corepressor
	00000041147	Brca2	breast cancer 2
	00000025577	Cbx2	chromobox homolog 2 (Drosophila Pc class)
	00000050107	Gsg2	germ cell-specific gene 2
	00000025001	Hells	helicase, lymphoid specific
	00000022394	L3mbtl2	l(3)mbt-like 2 (Drosophila)
	00000000708	Pcaf	p300/CBP-associated factor
	00000039354	Smarcal1	Swi/SNF-related matrix associated, actin-dependent regulator of chromatin, subfamily a-like 1
	00000017548	Suz12	suppressor of zeste 12 homolog (Drosophila)

Table 6. Overlapping gene sets in top-scoring (top-10%) GO and C2 gene sets in human and mouse

Gene set				Human		Mouse
	ID	Description	No. genes	MES score*	MES rank*	MES score*	MES rank*
GO	21	Androgen and estrogen metabolism	5	0.70257687	25	0.69758543	31
GO	43	GPCRs, Class C metabotropic glutamate, pheromone	5	0.66082051	46	0.68934427	36
GO	91	keratan sulfate metabolism	6	0.83775567	4	0.79486614	2
GO	93	cytochrome c oxidase activity	11	0.6525317	54	0.70751291	28
GO	131	lymphocyte antigen	7	0.70125548	26	0.64438202	59
GO	155	phospholipase A2 activity	5	0.64136441	62	0.62532692	84
GO	179	rRNA processing	10	0.67126842	40	0.73089631	17
GO	212	recombinational repair	6	0.66387678	41	0.779	4
GO	259	carbohydrate transport	8	0.59826911	88	0.64024026	68
GO	307	sulfuric ester hydrolase activity	5	0.64704872	59	0.7242533	20
GO	346	pyrimidine nucleotide biosynthesis	6	0.61171103	78	0.76543132	10
GO	357	carbohydrate uptake transporter activity	5	0.72988856	20	0.62485457	85
GO	478	glucose transporter activity	6	0.67512857	38	0.63845839	73
GO	533	eukaryotic translation initiation factor 3 complex	7	0.6330019	65	0.61142087	95
GO	576	inward rectifier potassium channel activity	6	0.62094236	71	0.64421257	61
GO	597	prostaglandin receptor activity	5	0.65357571	52	0.66498175	46
GO	622	cbb3-type cytochrome c oxidase	9	0.61553465	75	0.69467673	32
GO	632	RNA localization	5	0.62145465	70	0.72156698	23
GO	722	telomerase-dependent telomere maintenance	6	0.75142978	12	0.69981002	30
GO	749	mitotic recombination	6	0.66387678	42	0.779	5
GO	814	ribonuclease P activity	5	0.77639129	9	0.68632407	38
GO	847	telomere maintenance	7	0.68237918	31	0.70906119	25
GO	917	efflux permease activity	8	0.60147237	86	0.63864467	71
C2	1523	ctlPathway	6	0.75897778	3	0.63943534	32
C2	1575	GPCRs_Class_C_Metabotropic_glutamate_pheromone	5	0.66082051	15	0.68934427	22
C2	1597	il7Pathway	8	0.65596577	17	0.70575979	20
C2	1618	MAP00062_Fatty_acid_biosynthesis_path_2	6	0.62742037	23	0.67486056	24
C2	1648	MAP00531_Glycosaminoglycan_degradation	8	0.65314186	18	0.7370734	12
C2	1653	MAP00600_Sphingoglycolipid_metabolism	8	0.68997879	9	0.70789717	19
C2	1706	Pentose_Phosphate_Pathway	5	0.67256389	14	0.66508677	28
C2	1760	slrpPathway	5	0.6741084	13	0.68049977	23
C2	1817	ucalpainPathway	5	0.67720797	11	0.74026187	11
C2	1839	XINACT	6	0.57808044	40	0.72967644	15
C2	1864	BRCA_DOWN	6	0.75452668	4	0.7294046	16

GO, gene ontology gene set collection (www.geneontology.org); C2, MSigDb v1 C2 pathways gene set collection (database C2; www.broad.mit.edu/gsea/msigdb/msigdb_index.html).

*MES scores and ranks are determined separately for the GO and C2 gene set collections.

SI Materials and Methods

Generation of Conditional Brca1^F/+ ES Cells.
Brca1^F/+

ES cells were generated by sequential introduction of loxP sequences into Brca1 introns 3 and 13, respectively, resulting in a Brca1^F allele with floxed exons 5-13 (SI Fig. 7). First, a 16-kb genomic fragment containing a neomycin selection cassette flanked by loxP sites inserted into a unique SfuI site in Brca1 intron 13 was electroporated into ES cells. Southern blot analysis of neomycin-resistant ES clones was performed on EcoRV-digested genomic DNA with a Brca1 exon 14 probe, which detected, in addition to an ≈16-kb wild-type band, a 13.5-kb band derived from the targeted allele. After removal of the neomycin selection marker by transient Cre expression, a second round of targeting was performed with a 17-kb genomic fragment in which a neomycin selection cassette flanked by loxP sites had been inserted into a unique SmaI site in Brca1 intron 3. After neomycin selection, correctly targeted ES clones were identified by Southern blot analysis on BamHI-digested genomic DNA with a Brca1 exon 11 probe, revealing a 22-kb wild-type band and a 12-kb band for the targeted allele. A second round of transient Cre expression was used to remove the neomycin selection marker and identify ES clones in which both loxP sites had been inserted in cis on the same chromosome. Transient Cre expression in cis-targeted ES cells induced random recombination between the two loxP sites flanking the neomycin marker and the single loxP site in intron 13, resulting in occasional clones with a complete deletion of Brca1 exons 5-13 as detected by PCR with primers P1+P4. In addition, PCR reactions with primers P1+P2 and P3+P4 were performed to identify Brca1^F ES clones in which transient Cre expression had resulted in selective removal of the neomycin marker, leaving behind single loxP sites in Brca1 introns 5 and 13, respectively. Cre-mediated deletion of Brca1 exons 5-13 resulted in a shifted reading frame and the occurrence of multiple termination codons in exon 14 (data not shown).

Generation of Brca1^F Conditional Mouse Mutants.

Microinjection of 12-15 Brca1^F/+ ES cells into C57BL/6 blastocysts yielded germ-line chimeras, which were crossed with FVB/N mice to produce outbred heterozygous offspring. Cre-mediated deletion of the Brca1^F allele in the germ line was achieved by crossing Brca1^F/+ mice with Cre-deleter mice (1). The resulting Brca1D^/+ mice behaved normal and were not tumor-prone; however, intercrosses of heterozygous Brca1D^/+ mice on mixed 129/Ola and FVB/N genetic background failed to produce any homozygous Brca1D^/D offspring (data not shown), indicating that deletion of Brca1 exons 5-13 creates a Brca1-null allele that causes embryonic lethality.

Genotyping of Brca1^F and Brca1D Alleles by Southern Blotting.

High-molecular weight DNA was isolated from mouse tissues or ES cells by proteinase-K lysis and organic extraction with phenol-chloroform. Ten micrograms of genomic DNA digested with the appropriate restriction enzymes were used for Southern blot analysis. Blotting and hybridization procedures were carried out as described (2). Primers for amplification of the 310-nt Brca1 5' flanking probe were: forward primer, 5'-GAT AGT GCA ACT CTT AAA GC -3'; and reverse primer, 5'-ACA CGA CTA ACT CAT AAC TG -3'. Primers for amplification of the 86-nt Brca1 exon 14 probe were: forward primer, 5'-AGC CAA AAT TTG AAG AGC G -3'; and reverse primer, 5'-ATC CCT GAC TCG TCA TCT CC -3'.

Genotyping of Brca1^F and Brca1D Alleles by PCR.

The Brca1^F allele was detected by PCR amplification of (i) the loxP site in intron 3 with primers P1 and P2, yielding products of 545 bp and 390 bp for the floxed and wild-type alleles, respectively; or (ii) the loxP site in intron 13 with primers P3 and P4, yielding products of 620 bp and 494 bp for the floxed and wild-type alleles, respectively. Detection of the Brca1D allele with primers P1 and P4 yielded a 594-bp fragment. The primer sequences were as follows: P1, 5'-TAT CAC CAC TGA ATC TCT ACC G -3'; P2, 5'-GAC CTC AAA CTC TGA GAT CCA C -3'; P3, 5'-TAT TCT TAC TTC GTG GCA CAT C -3'; and P4, 5'-TCC ATA GCA TCT CCT TCT AAA C -3'. For all PCR reactions, thermocycling conditions consisted of 30 cycles of 30 sec at 94°C, 30 sec at 58°C, and 50 sec at 72°C. Reactions contained »200 ng of template DNA, 0.5 mM primers, 100 mM dNTPs, 2.5 units of TaqDNA polymerase, 2.5 mM MgCl₂, and 10 x PCR buffer in a 20-ml volume.

Immunohistochemistry.

Primary antibodies used were rat anti-CK8 (Troma-1 concentrate, DSHB products, 1:125), rabbit anti-CK14 (Babco; 1:10,000), rabbit anti-SMA (Lab Vision; 1:350), guinea pig anti-vimentin (RDI; 1:400), rabbit anti-cyclin D1(Santa Cruz; 1:200), rabbit anti-ERa (Santa Cruz; 1:2,000), mouse monoclonal anti-p63 (Lab Vision; 1:500), and rabbit anti-CK5 (Babco; 1:1,000). Secondary antibodies were biotin-conjugated anti-rat and anti-rabbit antibodies (Dako) and biotin-conjugated anti-guinea pig (Jackson ImmunoResearch).

RNA Extraction, Amplification, and Microarray Hybridization.

Total RNA was isolated with Trizol (Invitrogen) and purified with RNeasy minicolumns (Qiagen) according to the manufacturer's instructions. The integrity of RNA was verified by denaturing gel electrophoresis. Total RNA was reverse transcribed and amplified using the SuperScript III RNA amplification kit (Invitrogen). A tumor RNA pool, which consisted of equal amounts of amplified RNA from 12 different K14cre;p53^F/F mammary tumors, was used as a common reference for all microarray hybridizations. Oligonucleotide microarrays containing 31,769 longmer probes representing 18,173 genes and 32,829 transcripts (Operon Biotechnologies Inc, Huntsville, AL) were manufactured at the Netherlands Cancer Institute microarray facility. One microgram of amplified RNA was labeled with cyanine 5-conjugated ULS or cyanine 3-conjugated ULS (Kreatech Biotechnology, Amsterdam, The Netherlands). Hybridizations were performed in a solution of 5x saline sodium citrate and 25% formamide for 14-16 h at 42°C in a Tecan microarray hybridization station. Slides were washed, dried, and imaged with a laser scanner (Agilent Technologies). ImaGene software (BioDiscovery Inc, El Segundo, CA) was used for raw data quantification.

Microarray Data Normalization, Selection, and Filtering.

Background-corrected intensities were used to calculate log₂-transformed ratios, which were normalized using a Lowess fit per subarray as described (3). After normalization, a modified Rosetta error model (4) was used on dye-swapped pairs of hybridizations to calculate the weighted average ratio per gene and a P value indicating the chance a gene is falsely classified as deregulated. The error model was validated using self self-hybridizations that yielded no significantly regulated genes (data not shown). The number of gene features was reduced by excluding genes with >10% missing values. Also genes that showed significant changes in expression (log₂ ratio >1 or < -1) in <10% of the samples were excluded from the data sets. Using these criteria, 5,237 of 18,173 gene features were selected for unsupervised clustering and supervised classification.

Cross-Species Comparison of Microarray Data.

For cross-species comparison of gene expression signatures from human and mouse tumors, we used, besides our mouse expression data set containing 18,173 gene features, expression profiles of 16 ER-negative BRCA1 tumors and 28 ER-negative sporadic tumors from a previously published human data set containing 24,483 gene features (5). When genes were represented more than once on the mouse or human microarrays, the averaged expression ratios were used. We used BioMart (www.biomart.org/) to select 8,879 nonredundant genes, which were represented on both mouse and human microarray platforms. Before integration of the mouse and human data sets, the expression of each gene was standardized to mean ±SD of 0 ± 1 independently in both data sets as described (6). The number of gene features of mouse and human combined data sets was reduced by excluding genes with >10% missing values and also genes that showed significant changes in expression (log₂Ratio > 1 or < -1) in <10% of the samples. Using these criteria, 5,410 of 8,879 gene features were selected. Next, complete linkage hierarchical clustering employing Pearson correlation as distance measure was applied to group the 95 mouse and human breast tumors according to similarity in their gene expression profiles and the 5,410 genes according to similarity in their expression pattern over all 95 tumors. Methods used to determine significant co-clustering of human BRCA1-mutated breast cancers with mouse Brca1D^/D;p53D^/D tumors and of human ER-negative sporadic tumors with mouse p53D^/D tumors have been described in Results.

GSEA (www.broad.mit.edu/gsea/) was performed with gene set collections from the GO hierarchy (www.geneontology.org) and the C2 pathways collection of the Molecular Signature Database Version 1 (MSigDB; www.broad.mit.edu/gsea/msigdb/msigdb_index.html) as described previously (7). Of 8,879 nonredundant genes represented on both mouse and human microarray platforms, 7,127 genes were found to have annotations in the GO and/or MSigDB gene set collections. GO and MSigDB gene sets were selected when they contained at least five genes from the list of 7,127 nonredundant genes. The resulting collection of 980 GO and 424 MSigDB gene sets was used for independent GSEA on microarray expression data from human tumors and mouse tumors, respectively.

1. Schwenk F, Baron U, Rajewsky K (1995) Nucleic Acids Res 23:5080-5081.

2. Jonkers J, Meuwissen R, van der Gulden H, Peterse H, van der Valk M, Berns A (2001) Nat Genet 29:418-425.

3. Yang YH, Dudoit S, Luu P, Lin DM, Peng V, Ngai J, Speed TP (2002) Nucleic Acids Res 30:e15.

4. Weng L, Dai H, Zhan Y, He Y, Stepaniants SB, Bassett DE (2006) Bioinformatics 22:1111-1121.

5. van 't Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, Peterse HL, van der Kooy K, Marton MJ, Witteveen AT, et al. (2002) Nature 415:530-536.

6. Ellwood-Yen K, Graeber TG, Wongvipat J, Iruela-Arispe ML, Zhang J, Matusik R, Thomas GV, Sawyers CL (2003) Cancer Cell 4:223-238.

7. Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES, et al. (2005) Proc Natl Acad Sci USA 102:15545-15550.