SUPPLEMENTARY DATA SUPPLEMENTARY FIGURES: Supplementary Figure S1: Correlations of the 2-week change in the breast cancer hypoxia metagene with the 2-week change in AvERG and TFF1/pS2 A. Two-week change in the breast cancer hypoxia metagene versus 2-week change in AvERG. B. Two-week change in the breast cancer hypoxia metagene versus 2-week change in TFF1/pS2. 1 SUPPLEMENTARY TABLES: Supplementary Table S1: Annotation of the proliferation metagene Gene Accession symbol Number Gene name apolipoprotein B mRNA editing enzyme, catalytic APOBEC3B NM_004900 polypeptide-like 3B asp (abnormal spindle) homolog, microcephaly associated ASPM NM_018136 (Drosophila) AURKB NM_004217 aurora kinase B BIRC5 NM_001012270 baculoviral IAP repeat-containing 5 BUB1 NM_004336 budding uninhibited by benzimidazoles 1 homolog (yeast) budding uninhibited by benzimidazoles 1 homolog beta BUB1B NM_001211 (yeast) C21orf45 NM_018944 chromosome 21 open reading frame 45 CCNA2 NM_001237 cyclin A2 CCNB1 NM_031966 cyclin B1 CCNB2 NM_004701 cyclin B2 CCNE2 NM_057749 cyclin E2 CDC2 NM_001170407 cyclin-dependent kinase 1 CDC23 NM_004661 cell division cycle 23, yeast, homolog CDC7 NM_001134419 cell division cycle 7 homolog (S. cerevisiae) CDCA3 NM_031299 cell division cycle associated 3 CDCA8 NM_018101 cell division cycle associated 8 CDKN3 NM_001130851 cyclin-dependent kinase inhibitor 3 CENPA NM_001042426 centromere protein A CENPF NM_016343 centromere protein F, 350/400kDa (mitosin) CEP55 NM_001127182 centrosomal protein 55kDa CKAP2 NM_001098525 cytoskeleton associated protein 2 CKS2 NM_001827 CDC28 protein kinase regulatory subunit 2 CLCC1 NM_001048210 chloride channel CLIC-like 1 COP9 constitutive photomorphogenic homolog subunit 6 COPS6 NM_006833 (Arabidopsis) CSE1L NM_001316 CSE1 chromosome segregation 1-like (yeast) CTPS NM_001905 CTP synthase DDX39 NM_005804 DEAD (Asp-Glu-Ala-Asp) box polypeptide 39 DLG7 NM_014750 discs, large (Drosophila) homolog-associated protein 5 DNAJC9 NM_015190 DnaJ (Hsp40) homolog, subfamily C, member 9 DONSON NM_017613 downstream neighbor of SON DTL NM_016448 denticleless homolog (Drosophila) ECT2 NM_018098 epithelial cell transforming sequence 2 oncogene elongation of very long chain fatty acids (FEN1/Elo2, ELOVL1 NM_022821 SUR4/Elo3, yeast)-like 1 ENOSF1 NM_001126123 enolase superfamily member 1 2 EZH2 NM_004456 enhancer of zeste homolog 2 (Drosophila) FBXO5 NM_001142522 F-box protein 5 FEN1 NM_004111 flap structure-specific endonuclease 1 FOXM1 NM_021953 forkhead box M1 gamma-glutamyl hydrolase (conjugase, GGH NM_003878 folylpolygammaglutamyl hydrolase) GMNN NM_015895 geminin, DNA replication inhibitor HMGB2 NM_001130688 high-mobility group box 2 HMGB3 NM_005342 high-mobility group box 3 HMMR NM_001142556 hyaluronan-mediated motility receptor (RHAMM) HSPA14 NM_016299 heat shock 70kDa protein 14 KIAA0101 NM_001029989 KIAA0101 KIF11 NM_004523 kinesin family member 11 KIF14 NM_014875 kinesin family member 14 KIF23 NM_004856 kinesin family member 23 KIF2C NM_006845 kinesin family member 2C KIF4A NM_012310 kinesin family member 4A KNTC1 NM_014708 kinetochore associated 1 MAD2L1 NM_002358 MAD2 mitotic arrest deficient-like 1 (yeast) MCM2 NM_004526 minichromosome maintenance complex component 2 MCM6 NM_005915 minichromosome maintenance complex component 6 MCM7 NM_005916 minichromosome maintenance complex component 7 MELK NM_014791 maternal embryonic leucine zipper kinase MKI67 NM_001145966 antigen identified by monoclonal antibody Ki-67 MPP1 NM_001166460 membrane protein, palmitoylated 1, 55kDa MRPL47 NM_020409 mitochondrial ribosomal protein L47 MRS2L NM_020662 MRS2 magnesium homeostasis factor homolog-like MSH2 NM_000251 mutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli) MYBL2 NM_002466 v-myb myeloblastosis viral oncogene homolog (avian)-like 2 NEK2 NM_002497 NIMA (never in mitosis gene a)-related kinase 2 NUP155 NM_004298 nucleoporin 155kDa NUSAP1 NM_001129897 nucleolar and spindle associated protein 1 OIP5 NM_007280 Opa interacting protein 5 ORC6L NM_014321 origin recognition complex, subunit 6 PBK NM_018492 PDZ binding kinase POLE2 NM_001197330 polymerase (DNA directed), epsilon 2 (p59 subunit) PRC1 NM_003981 protein regulator of cytokinesis 1 PSME4 NM_014614 proteasome (prosome, macropain) activator subunit 4 RACGAP1 NM_001126103 Rac GTPase activating protein 1 RAD51AP1 NM_001130862 RAD51 associated protein 1 RFC3 NM_002915 replication factor C (activator 1) 3, 38kDa RFC4 NM_002916 replication factor C (activator 1) 4, 37kDa RPL39L NM_052969 ribosomal protein L39-like RPP40 NM_006638 ribonuclease P/MRP 40kDa subunit RRM2 NM_001034 ribonucleotide reductase M2 3 SEPHS1 NM_001195602 selenophosphate synthetase 1 solute carrier family 4, sodium bicarbonate cotransporter, SLC4A5 NM_021196 member 5 SRPK1 NM_003137 SRSF protein kinase 1 STIL NM_001048166 SCL/TAL1 interrupting locus STMN1 NM_001145454 stathmin 1 TACC3 NM_006342 transforming, acidic coiled-coil containing protein 3 TFRC NM_001128148 transferrin receptor (p90, CD71) TOP2A NM_001067 topoisomerase (DNA) II alpha 170kDa TPX2 NM_012112 TPX2, microtubule-associated, homolog (Xenopus laevis) TRIP13 NM_001166260 thyroid hormone receptor interactor 13 TTK NM_001166691 TTK protein kinase UBE2C NM_007019 ubiquitin-conjugating enzyme E2C UNG NM_003362 uracil-DNA glycosylase VRK1 NM_003384 vaccinia related kinase 1 WDR12 NM_018256 WD repeat domain 12 ZWINT NM_001005413 ZW10 interactor Supplementary Table S2: Proliferation-associated genes in the original breast cancer metagene Gene Accession Gene name symbol number ADM NM_001124 Adrenomedullin BTG3 NM_006806 BTG family, member 3 BUB1 NM_004336 BUB1 budding uninhibited by benzimidazoles 1 homolog (yeast) CCNB1 NM_031966 Cyclin B1 CCNB2 NM_004701 Cyclin B2 CDC2 NM_033379 Cell division cycle 2, G1 to S and G2 to M CDC20 NM_001255 Cell division cycle 20 homolog (S. cerevisiae) CDKN3 NM_005192 Cyclin-dependent kinase inhibitor 3 (CDK2-associated dual specificity phosphatase) CEP55 NM_018131 Centrosomal protein 55kDa DLG7 NM_014750 Disc large (Drosophila) homolog-associated protein 5 GGH NM_003878 Gamma-glutamyl hydrolase (conjugase, folylpolygammaglutamyl hydrolase) HMGB3 NM_005342 High-mobility group box 3 KIF4A NM_012310 Kinesin family member 4A MAD2L1 NM_002358 MAD2 mitotic arrest deficient-like 1 (yeast) MCTS1 NM_014060 Malignant T cell amplified sequence 1 MELK NM_014791 Maternal embryonic leucine zipper kinase MIF NM_002415 Macrophage migration inhibitory factor (glycosylation- inhibiting factor) NUP155 NM_004298 Nucleoporin 155kDa 4 PTTG1 NM_004219 Pituitary tumor-transforming 1 RACGAP1 NM_013277 Rac GTPase activating protein 1 RRM2 NM_001034 Ribonucleotide reductase M2 polypeptide STK6 NM_198434 Aurora kinase A TFRC NM_003234 Transferrin receptor (p90, CD71) TPX2 NM_012112 TPX2, microtubule-associated, homolog (Xenopus laevis) Supplementary Table S3: Annotation of the breast cancer hypoxia metagene excluding proliferation-associated genes Gene symbol Accession Gene name Meta- number connectivity score PGAM1 NM_002629 Phosphoglycerate mutase 1 (brain) 1.00 GARS NM_002047 Glycyl-tRNA synthetase 1.00 BNIP3 NM_004052 BCL2/adenovirus E1B 19kDa interacting 1.00 protein 3 LDHA NM_005566 Lactate dehydrogenase A 1.00 P4HA1 NM_000917 Procollagen-proline, 2-oxoglutarate 4- 1.00 dioxygenase (proline 4-hydroxylase), alpha polypeptide I GPI NM_000175 Glucose phosphate isomerase 0.99 NDRG1 NM_006096 N-myc downstream regulated 1 0.99 GAPDH NM_002046 glyceraldehyde-3-phosphate 0.99 dehydrogenase DDIT4 NM_019058 DNA-damage-inducible transcript 4 0.99 VEGF NM_001025366 vascular endothelial growth factor A 0.99 PFKP NM_002627 Phosphofructokinase, platelet 0.99 LOC388642 XM_934933 TPI1 pseudogene 0.99 PGK1 NM_000291 Phosphoglycerate kinase 1 0.99 ENO1 NM_001428 Enolase 1, (alpha) 0.98 DSCR2 NM_203433 proteosome assembly chaperone 1 0.98 SLC16A3 NM_004207 Solute carrier family 16, member 3 0.98 (monocarboxylic acid transporter 4) PRDX4 NM_006406 Peroxiredoxin 4 0.98 SLC2A1 NM_006516 Solute carrier family 2 (facilitated glucose 0.98 transporter), member 1 AK3L1 NM_016282 Adenylate kinase 3 like 1 0.97 GOLT1B NM_016072 Golgi transport 1 homolog B (S. 0.97 cerevisiae) RANBP1 NM_002882 RAN binding protein 1 0.97 RALA NM_005402 V-ral simian leukemia viral oncogene 0.97 homolog A (ras related) RIS1 NM_015444 transmembrane protein 158 0.97 SEC61G NM_001012456 Sec61 gamma subunit 0.97 ENY2 NM_020189 Enhancer of yellow 2 homolog 0.97 5 (Drosophila) MRPS17 NM_015969 Mitochondrial ribosomal protein S17 0.97 MTFR1 NM_014637 Mitochondrial fission regulator 1 0.97 MRPL15 NM_014175 Mitochondrial ribosomal protein L15 0.97 ANKRD37 NM_181726 Ankyrin repeat domain 37 0.97 CTSL2 NM_001333 Cathepsin L2 0.97 SLC7A5 NM_003486 Solute carrier family 7 (cationic amino 0.97 acid transporter, y+ system), member 5 MMP1 NM_002421 Matrix metallopeptidase 1 (interstitial 0.96 collagenase) PSMB5 NM_002797 Proteasome (prosome, macropain) 0.96 subunit, beta type, 5 TMEM70 NM_017866 Transmembrane protein 70 0.96 IMPAD1 NM_017813 Inositol monophosphatase domain 0.96 containing 1 PDIA6 NM_005742 Protein disulfide isomerase family A, 0.96 member 6 MRPL13 NM_014078 Mitochondrial ribosomal protein L13 0.96 IL8 NM_000584 interleukin 8 0.96 MTCH2 NM_014342 Mitochondrial carrier homolog 2 (C. 0.96 elegans) PSMA5 NM_002790 Proteasome (prosome, macropain) 0.95 subunit, alpha type, 5 KIF20A NM_005733 Kinesin family member 20A 0.95 ATP1B3 NM_001679 ATPase, Na+/K+ transporting, beta 3 0.95 polypeptide ATP5G3 NM_001002256 ATP synthase, H+ transporting, 0.95 mitochondrial F0 complex, subunit