Arsenic trioxide in ovarian cancer

ARSENIC TRIOXIDE IN OVARIAN CANCER ONG PEI SHI B.Sc (Pharm) Hons, NUS A THESIS SUBMITTED FOR THE DEGREE OF DOCTOR OF PHILOSOPHY DEPARTMENT OF PHARMACY NATIONAL UNIVERSITY OF SINGAPORE 2007 ACKNOWLEDGEMENTS I am indebted to the university and a large number of people for their invaluable assistance and support in the accomplishment of this thesis. In particular, I wish to express my sincere gratitude to: The National University of Singapore and Department of Pharmacy for providing me with a research scholarship during the course of this work. A/P Ho Chi Lui, Paul, my supervisor, for his kindness, patience, continuous guidance and encouragement throughout the course of this work. He has inspired me with his enthusiasm and has shown me the perseverance needed to good research. I have benefited immensely from his insight and his wide scientific knowledge. A/P Chan Sui Yung, my co-supervisor, for her kindness, guidance, concern, invaluable support and understanding. Thank you for believing in me, for being my mentor and friend. A/P Victor Yu and Dr Wong Siew Cheng, from IMCB, Singapore for the kind gift of the plasmid containing the Bclxl cDNA and assistance in the 3H thymidine uptake study, respectively. Ms Ting Wee Lee from Department of Pharmacology, NUS for her help with the use of the scintillation counter. Mrs Phang Beng Choo from the Laboratory of Environmental and Civil Engineering, NTU for her guidance in the use of the high pressure asher. Ms Ng Swee Eng, Mr Tang Chong Wing, Ms Ng Sek Eng, Ms Wong Mei Yin and Mrs Tham-Wong Pheng for the excellent technical support. Mrs Teo Say Moi, Ms Chew Ying Ying, Ms Napsiah Bte Suyod, Auntie Hua Yeong and Auntie Jenny for assisting me in numerous different ways. Ms Wong Lilian and Ms Tan Mui Ling for their encouragement and concern. It has been a very fun and enjoyable experience working with both of you. My seniors and fellow postgraduate students, with special thanks to Anandroop and Perry for their friendship and comaradie. My grandmother, for her love and care, especially during those difficult early childhood years. My parents, whom I delicate this work to, for their unconditional love, selflessness, support, encouragement and sacrifices they have made for me. My sister, brother-in-law and brother for all their help and constant encouragement and my little nephew, Kahao, whose presence and laughter never fails to brighten up my day. Table of Contents I TABLE OF CONTENTS CONTENTS PAGE Table of Contents …………………………………………………… Summary ……………………………………………………………… Publications and Conference Abstracts …………………………… List of Figures ………………………………………………………… List of Tables …………………………………………………………. Abbreviations … …………………………………………………… I VII X XII XV XVII Chapter Introduction ………………………………………… … 1.1 General Concepts of Cell Death Processes in Cancer Biology …… 1.1.1 Cellular Homeostasis and Overview of Cell Death Processes. 1.1.2 Definition, Morphological and Biochemical Characterization of Apoptosis, Autophagy and Necrosis …………………… . 1.1.3 Molecular Regulation of Apoptotic Cell Death …………… . 1.1.4 Death Programs Beyond Caspases: Caspase-Independent Cell Death ………………………………………………………… 1.1.5 PCD: Significance in Cancer Development and Treatment … 1.2 Cellular Antioxidant System and Glutathione ………………… . 1.2.1 Cellular Redox Regulation and Chemotherapy …………… . 1.2.2 Cellular GSH System – Biochemistry and Cellular Regulation 1.2.3 The Role of GSH in Oxidative Stress, Detoxification and PCD ………………………………………………………… 1.2.4 The Role of GSH in Disease and Cancer Chemotherapy …… 1.3 Ovarian Cancer … …………………………………………… . 1.3.1 Ovarian Cancer and Chemotherapy …………………………. 1.3.2 Cddp: Mode of Cytotoxic Action and Mechanisms of Resistance ………………………………………………… 1.3.3 Paclitaxel: Mode of Cytotoxic Action and Related Toxicity Issues ……………………………………………… 1.3.4 Investigational Agents for Ovarian Cancer Chemotherapy …. 1.4 Arsenic Trioxide and Cancer Chemotherapy …………………… . 1.4.1 Arsenical Compounds, their Reactivity, Biotransformation And Cellular Uptake ……………………………………… 1.4.2 Carcinogenic Effects and Therapeutic History of Arsenical Compounds 1.4.3 Anticarcinogenic Mechanisms of As2O3 …………………… 1.5 Statement of Purpose …………………………………………… . 1 18 23 24 24 27 31 33 35 35 37 42 45 49 49 51 55 59 Table of Contents Chapter Comparison of the Cytotoxicity Profiles of As2O3 and Paclitaxel in Ovarian Cancer and Normal Cells and Investigation of the Apoptotic and Cell Cycle Effects of As2O3 in Ovarian Cancer Cells ………………………………………………………… . 2.1 Introduction ……………………………………………………… . 2.2 Materials and Methods ……………… ………………………… 2.2.1 Materials ……………………………………………………. 2.2.2 Cell Lines and Cell Culture …………………………………. 2.2.3 Growth Inhibition and Cytotoxicity Measured by Fluorometric Microculture Cytotoxicity Assay …………… 2.2.3.1 Correlation between Cell Numbers and Fluorescence Intensity ………………………………………………… 2.2.3.2 FMCA ……………………………………… .……… … 2.2.4 Cell Morphology Evaluation ……………………………… . 2.2.4.1 Phase Contrast Microscopy ……………………………… 2.2.4.2 Confocal Microscopy ……………………………………. 2.2.5 Analysis of Apoptosis Rate and Cell Cycle Distribution by Flow Cytometry …………………………………………… 2.2.6 Statistics …………………………………………………… 2.3 Results ……………………………………………………………. 2.3.1 Linear Relationship Between FDA Fluorescence and Cell Number …………………………………………………… . 2.3.2 Cytotoxicity Profiles of As2O3 and Paclitaxel in Ovarian Tumour and Normal Cell Lines . 2.3.3 Reduction in Cell Number and Apoptosis Induction in As2O3 Responsive Ovarian Tumour Cells ………………………… 2.3.4 Time- and Concentration-Dependent Increase in Apoptotic Effects of As2O3 in OVCAR-3 Cells . 2.3.5 Low Concentrations of As2O3-Induced G2/M Phase Cell Cycle Arrest in OVCAR-3 Cells …………………………… 2.4 Discussion ……………………………………………………… Chapter The Role of Caspases, Antioxidants, Bcl2, Bclxl, Bax, Mitochondria and AIF in Arsenic-Induced Ovarian Cancer Cell Death ………………………………………………………………… 3.1 Introduction……………………………………………………… 3.2 Materials and Methods ……………… ………………………… 3.2.1 Materials …………………………………………………… . 3.2.2 Cell Culture and Transfection ……………………………… . 3.2.3 Quantification of Cell Death …………………………………. 3.2.4 Measurement of Caspase Activity ………………………… 3.2.5 Western Blotting …………………………………………… . 3.2.6 Isolation of RNA and Quantitative Polymerase Chain Reaction ……………………………………………………… 3.2.7 Measurement of ΔΨm ……………………………………… . 3.2.8 Localization of AIF by Immunofluorescence …………… . II 63 63 65 65 66 66 66 67 68 68 68 69 70 70 70 72 74 83 84 85 89 89 91 91 91 92 92 93 93 94 95 Table of Contents 3.2. Statistics ………………………………………………… . 3.3 Results ……………………………………………………………. 3.3.1 Cell Death Induced by As2O3 Is Caspase-Independent 3.3.2 As2O3-Mediated Cell Kill Occurred Independently of ROS in Ovarian Cancer Cells …………………………………… 3.3.3 Both Bclxl Protein and Gene Expression Were Consistently Down-Regulated In Arsenic Sensitive Cell Lines While Bcl2 and Bax Protein and Gene Expression Remained Unchanged In Response to Low As2O3 Concentration …………………. 3.3.4 Bclxl Overexpression Partially Protected Against ArsenicInduced Cytotoxicity ……………………………………… . 3.3.5 Depolarization of ΔΨm in a Fraction of OVCAR-3 Cells after As2O3 Treatment ………………………………………. 3.3.6 AIF Translocation in a Fraction of OVCAR-3 Cells After As2O3 Treatment ……………………………………………. 3.4 Discussion……………………………………………………… Chapter Correlation of Intracellular GSH Levels to ArsenicInduced Cell Death And Effects of GSH Modulating Agents in Enhancing The Cytotoxicity of As2O3 . 4.1 Introduction ………………………………………………….…… 4.2 Materials and Methods ……………… ………………………… 4.2.1 Chemicals …………………………………………………… 4.2.2 Cell Lines …………………………………………………… 4.2.3 3H-Thymidine Uptake Study ……………………………… . 4.2.4 Determination of Intracellular GSH Content ……………… 4.2.5 Assay For Cellular GPx Level ……………………………… 4.2.6 Western Blotting for Cellular CAT Level ………………… 4.2.7 Measurement of Cellular AA Uptake ………………………. 4.2.8 Measurement of Intracellular Arsenic Concentration ………. 4.2.9 Effects of Antioxidants on the Cytotoxicity of Combined Treatments ………………………………………………… . 4.2.10 Statistics…………………………………………………… . 4.3 Results…………………………………………………………… . 4.3.1 Correlation of Intracellular GSH Levels in Ovarian Cancer Cells and Normal Fibroblast Cells to their Sensitivity to As2O3 Treatment ……………………………………………. 4.3.2 BSO and Pharmacological Doses of AA Sensitized Ovarian Tumor Cells to the Cytotoxic Effects of As2O3 ……………… 4.3.3 Selective Kill of Ovarian Cancer Cells Over Normal Fibroblast Cells Using Clinically Achievable Concentrations of As2O3 with BSO and Pharmacologic Doses of AA with As2O3 ……………………………………………………… 4.3.4 JAM Cells Were Able to Accumulate AA Better Than OVCAR and OVCAR-3 Cells………………………………. III 95 96 96 98 102 106 108 109 110 114 114 115 115 116 116 117 117 118 119 120 121 121 122 122 123 131 132 Table of Contents 4.3.5 Combined As2O3 with BSO But Not Pharmacological Dose of AA Results in Increase in Apoptosis Induction… … 4.3.6 Reduction of Intracellular GSH Levels by BSO But Not Pharmacological Doses of AA in Ovarian Cancer Cells ……. 4.3.7 Effects of NAC, CAT and BHA on BSO or AA Augmentation of As2O3-Mediated Cell Kill ………………… 4.3.8 Sensitivity of Ovarian Cancer Cells to Pharmacological Doses of AA and As2O3 Treatment Was Related to Cellular Antioxidant Enzyme Levels …………………………………. 4.3.9 Increase in Intracellular Arsenic Accumulation Following Concurrent BSO and As2O3 Treatment ……………………… 4.4 Discussion ………………………………………………………. Chapter Establishment of an Arsenic Resistant OVCAR-3 Cell Line, OVCAR-3/AsR and Investigations of the Gene Expression Changes After Acute and Chronic Arsenic Treatment Using Microarray Analysis . 5.1 Introduction ……………………………………………………… 5.2 Materials and Methods ……………… ………………………… . 5.2.1 Materials ……………………………………………………. 5.2.2 Establishment of Arsenic Resistant OVCAR-3 Cell Line … 5.2.3 Cell Treatment, RNA Isolation, Quality Assessment and Microarray Hybridisation and Image Acquisition ………… 5.2.4 Data Mining For Microarray Study ………………………… 5.2.5 Pathway Analysis of Differentially Expressed Genes ……… 5.3 Results …………………………………………………………… . 5.3.1 Establishment of Arsenic Resistant OVCAR-3 Cell Line, OVCAR-3/AsR …………………………………………… . 5.3.2 Lack of Cross Resistance of OVCAR-3/AsR to Cddp and Paclitaxel ……………………………………………………. 5.3.3 Microarray Profiling of the Gene Expression Changes After Acute and Chronic As2O3 Treatment ……………………… 5.3.4 Network and Pathway Analysis of Differentially Expressed Genes Between Parental OVCAR-3 Cells versus Resistant OVCAR-3/AsR Cells ……………………………………… . 5.4 Discussion …………………………………………………………. IV 133 135 138 142 144 145 151 151 152 152 152 153 155 155 156 156 159 160 174 177 Chapter Investigations of Synergistic and Antagonistic Cytotoxic Drug Combinations of As2O3 and Cddp with HDACIs, SAHA and MS-275 ……………………………………………………………… . 184 6.1 Introduction ……………………………………………………… 185 Table of Contents V 6.2 Materials and Methods ……………… ………………………… . 6.2.1 Chemicals ……………………………………………………. 6.2.2 Cell Lines and Cell Culture ………………………………… 6.2.3 Analysis of Drug Interaction ………………………………… 6.2.4 Sequence Dependent Interaction Between Cddp and HDACIs 6.2.5 Statistical Analysis ………………………………………… . 6.3 Results ……………………………………………………………. 6.3.1 Evaluation of The Sensitivities of OVCAR-3 and SKOV-3 Cells to Individual Drug Treatment After 48 hrs of Incubation …………………………………………………… 6.3.2 As2O3 and HDACIs Combinations Resulted in Antagonism while Cddp and HDACIs Combinations Interacted Synergistically in SKOV-3 and OVCAR-3 Cell Lines Following Simultaneous Drug Exposure ………………… . 6.3.3 Therapeutically Relevant Concentrations of SAHA and MS275 Achieved Synergism with Cddp in Ovarian Tumour Cells …………………………………………………………. 6.3.4 Synergistic Combinations Showed Selectivity for Ovarian Cancer Cells …………………………………………………. 6.3.5 Effects of Synergistic Combinations on Cell Morphology of OVCAR-3 and SKOV-3 Cells ………………………………. 6.3.6 Increased Apoptotic Cell Kill with Cddp and SAHA Combination in OVCAR-3 and SKOV-3 Cells and Cddp and MS-275 Combination in OVCAR-3 Cells ……………… 6.3.7 Enhanced Cell Kill with Cddp and SAHA and Cddp and MS-275 Synergistic Combinations Was Not Attributed to Cell Cycle Arrest …………………………………………… 6.3.8 Optimization of Combination Dosing Schedule Using OVCAR-3 Cells …… .……………………………………… 6.4 Discussion ……………………………………………………… . 185 185 186 186 187 188 189 Chapter Summary and Future Studies ………………………… 7.1 Summary ………………………………………………………… . 7.2 Future Studies …………………………………………………… . 7.2.1 Validation of Microarray Results With Real Time Polymerase Chain Reaction, Western Blotting and Intracellular GSH Measurement in OVCAR-3/AsR Cells ………………………. 7.2.2 Investigation of the Mode(s) of Non-Apoptotic PCD Induced by As2O3 in Ovarian Tumour Cells ………………………… 7.2.3 Identification of the Mode of Cell Death Induced By Pharmacological Concentrations of AA in Combination with As2O3 Using Electron Microscopic Study and Translation of the Use of this Drug Combination into an In Vivo Animal Model ………………………………………………………… 7.2.4 Targeted Delivery of BSO for Greater Tumour Cell Selectivity of BSO During Augmentation of the Drug Activity of As2O3 ……………………………………………………… 213 213 216 189 191 194 198 199 202 205 207 209 216 216 217 219 Table of Contents 7.2.5 Use of an IL1R Antagonist to Disrupt IL1A Mediated Chemoresistant Signalling in OVCAR-3/AsR Cells ……… Bibliography Appendices VI 219 221 Summary VII SUMMARY Arsenic trioxide (As2O3) has been proven to induce clinical remission in patients with acute promyelocytic leukaemia without severe side effects. Previously, Du and Ho showed that arsenical compounds were able to induce cytotoxicity and apoptosis in both cisplatin (Cddp)-sensitive and -resistant ovarian cancer cells (Du and Ho, 2001). In the present study, the potential use of As2O3 for ovarian cancer treatment, its mechanisms of action, the factors responsible for As2O3 resistance in OVCAR-3 cells and the combined use of As2O3 with histone deacetylase inhibitors (HDACIs) were evaluated. It was found that As2O3 displayed a similar pattern of cytotoxic effect with paclitaxel against various Cddp-sensitive and resistant ovarian cancer cell lines. This further reinforced its potential usefulness for the treatment of platinum refractory disease, especially in patients who cannot tolerate paclitaxel therapy. Investigations into the effects of As2O3 confirmed apoptosis induction. In OVCAR-3 cells, apoptosis induction was a late event that was time and concentration-dependent. It was accompanied by cell cycle arrest at either the G2/M or S phase that was again concentration-dependent. Cell death induced by As2O3 was found to be caspase- and oxidative stress independent. It was accompanied by the dissipation of the mitochondrial membrane potential and the mitochondria to nucleus translocation of caspase-independent apoptosis inducing factor in a fraction of arsenic-treated cells. In addition, As2O3 treatment was associated with the down-regulation of Bclxl gene and protein levels. Ectopic expression of Bclxl in OVCAR-3 cells not only completely blocked apoptosis but conferred a greater protection against cell death beyond Summary VIII apoptosis induction. This suggests that multiple complex modes of cell death processes might be involved in As2O3-mediated ovarian cancer cell death. Intracellular glutathione (GSH) levels were found to be correlated to the arsenic sensitivities of the ovarian cancer cell lines studied. Modulation of intracellular GSH levels using buthionine sulfoximine (BSO) resulted in a reactive oxygen species (ROS) independent augmentation of arsenic-induced cell death. It also caused a net increase in cellular arsenic levels, suggesting that transporter mediated efflux of arsenic-GSH conjugate may play a role in determining arsenic sensitivity of ovarian carcinoma cells. In this study, physiological level of ascorbic acid (AA), another reported GSH modulator, was unable to modulate the intracellular GSH levels of ovarian tumour cells. Likewise, pharmacological levels of AA did not bring about GSH reduction but increased arsenic-induced cell kill in part through ROS. Microarray analysis of gene expression patterns of parental OVCAR-3 cells after acute arsenic treatment further revealed the novel role of endoplasmic recticulum (ER) stress in arsenic-induced cell death. Accompanying the induction of ER stress, parental OVCAR-3 cells mounted a survival response to increase intracellular GSH levels. This formed another rationale with which BSO was able to effectively enhanced arsenicinduced cell kill. It further revealed the existence of a complex crosstalk between the mitochondria and ER in response to acute As2O3 exposure. In arsenic-resistant OVCAR-3 (OVCAR-3/AsR) cells, gene expression analysis showed the involvement of multiple factors in mediating As2O3 chemoresistance. Of particular importance was the PH_hs_0022469 PH_hs_0022539 PH_hs_0022560 PH_hs_0022589 PH_hs_0022632 PH_hs_0022734 PH_hs_0022739 PH_hs_0022779 PH_hs_0022919 PH_hs_0022944 PH_hs_0022977 PH_hs_0022999 PH_hs_0023101 PH_hs_0023398 PH_hs_0023411 PH_hs_0023504 PH_hs_0023550 PH_hs_0023568 PH_hs_0023584 PH_hs_0023602 PH_hs_0023636 PH_hs_0023739 PH_hs_0023764 PH_hs_0023894 PH_hs_0023937 PH_hs_0023962 PH_hs_0023967 PH_hs_0024008 PH_hs_0024009 PH_hs_0024014 PH_hs_0024015 PH_hs_0024092 PH_hs_0024094 PH_hs_0024164 PH_hs_0024170 PH_hs_0024307 PH_hs_0024364 GeneBank ID NM_005715 NM_006384 NM_005862 NM_003986 NM_007361 NM_016339 XM_114303 NM_017664 NM_013246 NM_006867 NM_153811 NM_003567 NM_033254 NM_006714 NM_138451 NM_014432 NM_004665 NM_015570 NM_001946 NM_178012 NM_001751 NM_152282 NM_002061 NM_021158 NM_006120 NM_052832 NM_017786 NM_182487 NM_002604 NM_003199 AL832164 NM_007129 NM_145035 XM_031553 NM_002272 NM_014857 - Entrez Gene Name UST CIB1 STAG1 BBOX1 NID2 RAPGEFL1 FRMD4B ANKRD10 CLC RBPMS SLC38A6 BCAR3 BOC SMPDL3A IQCD IL20RA VNN2 AUTS2 DUSP6 MGC8685 CARS ACPL2 GCLM TRIB3 HLA-DMA SLC26A7 FLJ20366 OLFML2A PDE7A TCF4 LOC283666 ZIC2 ADMP SR140 KRT4 RABGAP1L - Batch vs 24 hrs Fold vs 24 hrs p-value vs 48 hrs Fold 1.226 -1.073 1.218 -1.559 1.267 1.048 -1.034 -1.202 1.826 1.011 2.144 1.928 -3.841 1.477 -1.022 -1.403 -1.856 -1.112 2.221 1.092 1.217 -1.256 4.939 2.012 -2.098 -3.503 1.920 -1.503 -1.559 -1.412 1.157 1.260 -2.579 -1.112 -4.266 1.312 -1.609 0.216 0.636 0.105 0.0341 0.242 0.705 0.757 0.0880 0.0493 0.963 0.0676 0.0431 0.00792 0.0629 0.916 0.362 0.116 0.305 0.0283 0.703 0.135 0.135 0.0230 0.0411 0.0266 0.0101 0.0570 0.0368 0.0826 0.295 0.189 0.335 0.0269 0.408 0.0249 0.225 0.394 1.189 -1.014 -1.350 -1.586 1.215 1.421 -1.288 -1.274 1.400 1.333 2.104 1.620 -4.380 1.214 -1.229 -3.820 -3.316 -1.082 2.194 1.201 1.164 -1.298 3.817 2.399 -1.753 -4.992 2.148 -1.519 -1.862 -1.430 1.564 1.906 -4.333 -1.186 -6.642 1.221 -1.369 A vs 48 hrs p-value 0.0721 0.906 0.0211 0.00687 0.295 0.0841 0.0429 0.0242 0.0105 0.0509 0.0311 0.0508 0.00418 0.0204 0.156 0.116 0.0120 0.155 0.0210 0.333 0.055 0.0679 0.00835 0.00239 0.0477 0.00141 0.0268 0.0267 0.00729 0.0278 0.0344 0.0257 0.0120 0.0479 0.00266 0.0309 0.137 vs R vs R Fold p-value 4.697 2.134 -2.268 -4.296 2.337 2.148 -2.846 -2.219 3.007 2.608 2.077 2.522 -1.019 -3.717 2.859 1.723 3.319 -2.112 1.937 -4.489 -2.948 -5.893 3.817 -1.213 1.817 -3.634 1.382 -2.245 -2.224 -3.580 -3.196 6.229 -3.868 -2.172 6.936 2.661 6.962 0.00122 0.0161 0.0118 0.000651 0.00406 0.0169 0.0136 0.0407 0.00271 0.0101 0.0236 0.0133 0.631 0.0214 0.0126 0.0135 0.00626 0.000689 0.00685 0.00109 0.00311 0.00248 0.00697 0.0231 0.0130 0.00775 0.0620 0.00936 0.00353 0.00824 0.00268 0.00573 0.00308 0.00697 0.00211 0.0101 0.00409 Batch B vs 24 hrs Fold vs 24 hrs p-value vs 48 hrs Fold vs 48 hrs p-value 1.158 1.046 -1.146 -1.411 -1.056 1.164 -1.050 -1.123 2.115 1.172 1.781 1.544 -2.366 1.208 1.108 -1.746 -1.629 -1.105 1.485 -1.000 1.349 -1.313 4.008 2.150 -1.221 -2.996 1.446 -1.382 -1.187 -1.952 1.062 1.028 -2.461 -1.064 -4.038 -1.197 -1.864 0.397 0.778 0.197 0.174 0.740 0.223 0.823 0.430 0.0519 0.485 0.0562 0.0936 0.0519 0.149 0.425 0.143 0.180 0.273 0.148 1.000 0.252 0.139 0.0265 0.0519 0.290 0.0520 0.0718 0.188 0.180 0.134 0.126 0.770 0.0913 0.594 0.0311 0.308 0.150 1.573 1.074 -1.223 -1.246 1.256 1.310 -1.116 -1.088 2.083 1.259 2.169 1.469 -2.079 1.127 1.219 -2.266 -2.772 -1.013 2.022 1.078 1.698 -1.331 3.810 3.389 -1.065 -4.965 2.457 -1.353 -1.743 -2.043 2.000 1.309 -3.613 -1.251 -4.817 -1.656 -2.631 0.0217 0.371 0.0432 0.0165 0.0664 0.0560 0.379 0.401 0.0180 0.208 0.0133 0.0222 0.0317 0.229 0.128 0.0296 0.0469 0.835 0.0597 0.689 0.0740 0.0617 0.00942 0.00670 0.517 0.0107 0.0194 0.0216 0.0148 0.0846 0.0291 0.0414 0.00638 0.0544 0.00377 0.0473 0.0664 vs R vs R Fold p-value 5.096 2.197 -2.137 -3.565 5.901 2.191 -2.391 -2.015 3.351 2.408 2.305 2.268 1.250 -3.222 3.186 1.847 4.680 -2.422 1.407 -4.321 -2.159 -4.396 4.523 -1.003 2.398 -6.112 1.373 -2.746 -2.731 -3.553 -3.695 4.111 -3.298 -2.121 12.560 -3.003 5.244 0.00631 0.00933 0.0628 0.0297 0.0160 0.00711 0.0375 0.0200 0.00911 0.00945 0.00649 0.00359 0.0967 0.0512 0.0138 0.0318 0.0084 0.00677 0.0799 0.0160 0.0466 0.00307 0.00412 0.951 0.0152 0.0112 0.0368 0.00970 0.00478 0.0178 0.0349 0.0228 0.0247 0.00945 0.000887 0.638 0.000887 Appendix Phalanx Probe ID PH_hs_0024398 PH_hs_0024437 PH_hs_0024448 PH_hs_0024475 PH_hs_0024509 PH_hs_0024531 PH_hs_0024685 PH_hs_0024713 PH_hs_0024752 PH_hs_0024758 PH_hs_0024812 PH_hs_0024827 PH_hs_0024837 PH_hs_0024839 PH_hs_0024845 PH_hs_0024930 PH_hs_0024953 PH_hs_0024961 PH_hs_0024978 PH_hs_0025004 PH_hs_0025057 PH_hs_0025078 PH_hs_0025081 PH_hs_0025088 PH_hs_0025139 PH_hs_0025184 PH_hs_0025212 PH_hs_0025250 PH_hs_0025269 PH_hs_0025272 PH_hs_0025293 PH_hs_0025324 PH_hs_0025342 PH_hs_0025406 PH_hs_0025490 PH_hs_0025524 PH_hs_0025581 GeneBank ID NM_004207 NM_003810 NM_003730 NM_001099 NM_006820 NM_002037 NM_001846 NM_003034 NM_052941 NM_016105 NM_004304 NM_022817 NM_004631 NM_000132 NM_032466 NM_001565 NM_014234 NM_000350 NM_001394 NM_016831 NM_212474 NM_001449 NM_024907 NM_015993 NM_003108 NM_013343 NM_025080 NM_006097 NM_182729 NM_153365 NM_005269 NM_203447 NM_001845 Entrez Gene Name SLC16A3 TNFSF10 RNASET2 ACPP IFI44L FYN COL4A2 SIAT8A GBP4 FKBP7 ALK PER2 LRP8 F8 ASPH CXCL10 HSD17B8 ABCA4 DUSP4 PER3 FN1 FHL1 FBXO17 TM4SF11 SOX11 LOH3CR2A ASRGL1 MYL9 TXNRD1 FLJ90013 GLI DOCK8 COL4A1 Batch vs 24 hrs Fold vs 24 hrs p-value vs 48 hrs Fold 1.072 -1.765 1.056 -3.865 -2.066 1.677 -1.093 -1.122 -1.344 1.062 -2.387 -1.339 -1.401 -2.114 2.092 1.144 3.100 -1.876 2.339 -1.126 -1.603 3.012 -1.965 -1.201 1.238 1.149 -2.001 -1.141 -2.388 1.226 1.121 4.035 1.390 1.108 1.553 -1.134 1.086 0.568 0.0383 0.734 0.0393 0.0393 0.0269 0.214 0.386 0.192 0.714 0.0412 0.114 0.152 0.123 0.0492 0.299 0.0953 0.072 0.0383 0.257 0.112 0.0269 0.0283 0.0436 0.169 0.118 0.0408 0.210 0.0851 0.250 0.567 0.0314 0.0535 0.547 0.101 0.483 0.506 1.066 -2.801 1.413 -4.435 -2.372 1.490 -1.287 -1.164 -1.210 -1.266 -2.354 -1.522 -1.179 -1.781 2.073 -1.124 2.936 -1.994 1.883 -1.188 -1.605 3.183 -1.237 -2.218 1.406 1.365 -1.934 1.172 -2.156 1.024 1.450 3.716 1.343 1.210 2.002 -3.232 -1.082 A vs 48 hrs p-value 0.552 0.0107 0.0179 0.0107 0.0292 0.0339 0.0245 0.0699 0.0850 0.129 0.00899 0.0179 0.113 0.0351 0.0205 0.213 0.0245 0.00607 0.0143 0.228 0.0184 0.00577 0.0635 0.00786 0.0525 0.0629 0.0154 0.116 0.0230 0.860 0.0863 0.0105 0.0563 0.264 0.0454 0.0487 0.247 vs R vs R Fold p-value 5.350 1.061 2.677 1.252 -7.283 -2.538 2.406 -2.883 -2.924 -2.678 -3.259 -3.171 2.448 1.688 2.308 -3.295 3.826 5.196 1.461 -3.018 2.446 -5.686 -2.459 -1.984 -2.569 -3.031 -2.594 -4.750 -3.171 -3.718 -2.808 2.297 2.265 3.600 -1.427 4.804 -2.795 0.00301 0.183 0.00122 0.101 0.0114 0.0161 0.00202 0.00248 0.0034 0.00705 0.00655 0.00819 0.00819 0.0212 0.00598 0.0286 0.000651 0.00449 0.0174 0.00608 0.00433 0.00755 0.00450 0.00425 0.0102 0.00383 0.00995 0.00521 0.0122 0.00657 0.0104 0.0229 0.00521 0.00689 0.0835 0.00809 0.00624 Batch B vs 24 hrs Fold vs 24 hrs p-value vs 48 hrs Fold vs 48 hrs p-value 1.243 -1.468 1.039 -2.512 -2.332 1.479 -1.278 1.112 -1.093 -1.236 -1.678 -1.165 -1.066 -2.258 1.824 -1.117 2.328 -2.246 2.063 -1.084 -1.391 2.217 -2.139 -1.119 1.126 1.066 -1.677 -1.033 -1.760 -1.058 1.013 2.945 1.236 1.139 1.357 -1.290 1.077 0.428 0.111 0.268 0.0612 0.118 0.186 0.188 0.503 0.552 0.287 0.0913 0.347 0.293 0.0196 0.0630 0.553 0.136 0.0519 0.0210 0.733 0.121 0.0653 0.0311 0.186 0.252 0.241 0.120 0.851 0.082 0.841 0.961 0.0999 0.211 0.286 0.129 0.393 0.624 -1.214 -3.004 1.277 -3.340 -1.830 2.170 1.078 1.377 1.095 -1.785 -1.873 -1.373 1.035 -2.234 2.210 -1.133 2.225 -4.406 1.996 -1.328 -1.410 2.963 -1.306 -1.508 1.327 1.318 -1.709 1.191 -2.313 -1.138 1.115 3.439 1.036 1.166 2.738 -2.479 -1.032 0.349 0.0101 0.0165 0.00942 0.0752 0.0345 0.437 0.0944 0.414 0.0289 0.0250 0.0612 0.640 0.00767 0.0148 0.416 0.0611 0.0132 0.00789 0.233 0.0673 0.0251 0.0703 0.018 0.0251 0.0301 0.0315 0.0957 0.0218 0.541 0.537 0.0176 0.746 0.00975 0.0315 0.0642 0.763 vs R vs R Fold p-value 5.667 1.189 2.501 1.025 -5.435 -1.653 3.292 -2.481 -2.862 -3.058 -3.928 -3.034 2.553 -1.078 2.068 -2.623 2.656 3.434 1.668 -2.929 3.241 -5.801 -2.486 -2.055 -2.567 -3.116 -2.148 -4.515 -3.129 -4.191 -4.913 2.108 2.218 4.150 -1.674 5.378 -2.965 0.0212 0.0791 0.00964 0.785 0.0104 0.0532 0.00714 0.0258 0.0197 0.0297 0.00499 0.0338 0.00677 0.575 0.0151 0.0170 0.0259 0.00471 0.00723 0.0426 0.00726 0.0125 0.0237 0.00523 0.0209 0.0211 0.0148 0.00237 0.00853 0.0209 0.0124 0.0151 0.00365 0.0123 0.0375 0.0241 0.0162 Appendix Phalanx Probe ID PH_hs_0025588 PH_hs_0025607 PH_hs_0025690 PH_hs_0025701 PH_hs_0025782 PH_hs_0025799 PH_hs_0025826 PH_hs_0025862 PH_hs_0025869 PH_hs_0025875 PH_hs_0025907 PH_hs_0025925 PH_hs_0025967 PH_hs_0026045 PH_hs_0026095 PH_hs_0026211 PH_hs_0026354 PH_hs_0026357 PH_hs_0026522 PH_hs_0026578 PH_hs_0026589 PH_hs_0026600 PH_hs_0026605 PH_hs_0026662 PH_hs_0026765 PH_hs_0026808 PH_hs_0026823 PH_hs_0026843 PH_hs_0026899 PH_hs_0027024 PH_hs_0027041 PH_hs_0027066 PH_hs_0027088 PH_hs_0027090 PH_hs_0027093 PH_hs_0027127 PH_hs_0027137 GeneBank ID NM_020453 NM_004998 NM_017842 NM_001431 NM_001744 NM_000904 NM_002065 NM_014883 NM_002589 NM_000140 NM_033138 NM_003937 NM_025130 NM_022036 NM_014391 NM_023938 NM_002627 NM_005965 NM_145909 NM_006500 NM_006317 NM_001955 NM_016356 NM_006512 NM_004613 NM_024896 NM_014243 NM_000359 NM_002423 NM_001550 NM_031430 NM_020770 NM_005704 NM_004282 NM_018988 Entrez Gene Name ATP10D MYO1E FLJ20489 EPB41L2 CAMK4 NQO2 GLUL FAM13A1 PCDH7 FECH CALD1 KYNU FLJ22761 GPRC5C ANKRD1 SARG PFKP MYLK ZNF323 MCAM BASP1 EDN1 DCDC2 SAA4 TGM2 KIAA1815 ADAMTS3 TGM1 MMP7 IFRD1 RILP CGN PTPRU BAG2 GFOD1 Batch vs 24 hrs Fold vs 24 hrs p-value vs 48 hrs Fold 1.272 1.265 -1.166 1.576 -1.166 -1.308 3.704 1.201 -1.656 1.118 3.336 1.218 3.227 2.448 1.387 -1.276 1.189 -1.455 1.350 -1.895 1.732 1.173 -1.213 -1.682 -1.074 1.355 -1.356 1.464 -1.141 -1.281 1.501 2.152 1.100 -1.964 1.026 1.829 -2.326 0.0246 0.0564 0.704 0.210 0.0566 0.159 0.0101 0.0569 0.0493 0.689 0.0372 0.452 0.0283 0.0440 0.0312 0.177 0.134 0.431 0.179 0.0665 0.0668 0.169 0.196 0.0597 0.820 0.184 0.169 0.147 0.429 0.310 0.0941 0.0227 0.778 0.0661 0.630 0.0283 0.0481 -1.044 1.112 -1.090 1.281 -1.443 -1.867 3.894 1.054 -2.973 1.249 3.502 -1.360 2.148 3.037 1.148 -1.763 1.343 -1.414 1.505 -2.069 1.921 1.184 -1.009 -2.319 -1.496 1.842 -1.774 1.535 -2.328 -1.079 -1.352 1.678 1.383 -2.435 1.927 1.560 -2.543 A vs 48 hrs p-value 0.587 0.192 0.139 0.0212 0.0107 0.0074 0.0046 0.191 0.0120 0.114 0.0127 0.0168 0.0131 0.0120 0.122 0.071 0.0262 0.133 0.0344 0.0254 0.00892 0.116 0.950 0.0161 0.0333 0.0379 0.0524 0.0845 0.0228 0.348 0.0245 0.0141 0.0980 0.0154 0.00786 0.0120 0.00468 vs R vs R Fold p-value 3.968 2.658 -2.408 2.189 -2.065 -3.325 3.414 -3.211 -2.856 4.469 1.958 -3.336 2.076 1.697 2.068 -4.543 2.173 3.001 4.018 -4.474 -2.920 -3.010 -3.443 -3.539 -2.237 10.820 4.013 3.590 -1.170 2.731 2.568 -1.907 2.588 -1.378 3.352 2.574 -1.227 0.00983 0.00245 0.00383 0.00248 0.00516 0.00438 0.00276 0.00145 0.000651 0.00717 0.00771 0.00384 0.00809 0.0108 0.00986 0.0141 0.00481 0.0120 0.00934 0.00402 0.00481 0.00269 0.00611 0.0112 0.00455 0.00867 0.00614 0.00763 0.258 0.00269 0.00675 0.00806 0.00383 0.0768 0.0129 0.00225 0.0139 Batch B vs 24 hrs Fold vs 24 hrs p-value vs 48 hrs Fold vs 48 hrs p-value -1.021 1.239 -1.273 1.323 -1.228 -1.303 2.785 -1.049 -1.441 1.056 2.144 -1.022 1.618 1.612 1.507 -1.198 1.363 -1.665 1.269 -1.887 1.744 1.079 1.042 -1.757 -1.614 1.223 -1.214 1.412 -1.220 -1.438 1.232 2.000 -1.120 -1.657 -1.013 1.565 -1.771 0.927 0.303 0.304 0.197 0.199 0.186 0.0822 0.582 0.145 0.678 0.0731 0.542 0.108 0.0913 0.0860 0.425 0.103 0.188 0.134 0.0973 0.0890 0.493 0.873 0.0913 0.123 0.583 0.483 0.111 0.372 0.188 0.0822 0.0769 0.354 0.118 0.935 0.115 0.0693 -1.555 1.323 -1.239 1.082 -1.512 -1.660 2.953 -1.063 -2.689 1.187 2.252 1.024 1.317 2.910 1.387 -1.680 1.300 -2.085 1.263 -1.509 1.830 1.009 1.049 -2.493 -1.735 1.259 -1.301 1.904 -2.502 -1.022 -1.692 2.245 1.038 -2.257 -1.096 1.270 -2.069 0.101 0.120 0.211 0.420 0.0333 0.0673 0.0287 0.617 0.0287 0.157 0.0166 0.425 0.101 0.0155 0.0523 0.0497 0.192 0.0555 0.0549 0.0414 0.0289 0.880 0.793 0.0141 0.0478 0.433 0.292 0.0216 0.0468 0.849 0.0751 0.0359 0.429 0.0280 0.341 0.160 0.0291 vs R vs R Fold p-value 3.817 2.264 -2.523 2.434 -2.230 -2.460 2.567 -2.364 -2.210 3.971 1.563 -3.066 2.335 1.706 2.871 -3.728 2.273 3.200 3.649 -4.406 -2.967 -4.086 -2.46 -6.346 -2.343 9.186 5.914 5.031 -1.193 2.359 2.729 -1.181 2.310 -1.328 2.361 2.266 -1.419 0.0171 0.0434 0.0173 0.0155 0.0274 0.0121 0.0124 0.00359 0.0141 0.00523 0.0317 0.0613 0.0297 0.0349 0.00677 0.0939 0.0139 0.0211 0.00238 0.0218 0.0287 0.00384 0.0440 0.0267 0.0415 0.018 0.0286 0.0114 0.284 0.0115 0.0226 0.0823 0.0431 0.114 0.00653 0.0154 0.0253 Appendix Phalanx Probe ID PH_hs_0027158 PH_hs_0027161 PH_hs_0027162 PH_hs_0027200 PH_hs_0027214 PH_hs_0027279 PH_hs_0027301 PH_hs_0027323 PH_hs_0027514 PH_hs_0027536 PH_hs_0027544 PH_hs_0027715 PH_hs_0027908 PH_hs_0028098 PH_hs_0028187 PH_hs_0028196 PH_hs_0028696 PH_hs_0028708 PH_hs_0028763 PH_hs_0028818 PH_hs_0028833 PH_hs_0028850 PH_hs_0028931 PH_hs_0028942 PH_hs_0028961 PH_hs_0028988 PH_hs_0029016 PH_hs_0029204 PH_hs_0029218 PH_hs_0029236 PH_hs_0029418 PH_hs_0029660 PH_hs_0029732 PH_hs_0029926 PH_hs_0029946 PH_hs_0029964 PH_hs_0029983 GeneBank ID NM_006756 NM_015149 NM_002394 BC010607 NM_003843 NM_020698 NM_024909 NM_021127 NM_030754 NM_000916 NM_002264 NM_000096 NM_024692 NM_021105 NM_001735 NM_000346 NM_018389 NM_003512 NM_016262 NM_003551 NM_000165 NM_003739 NM_000227 NM_001233 NM_144684 NM_018159 NM_006096 NM_000846 NM_153699 Entrez Gene Name TCEA1 RGL1 SLC3A2 MGC18216 SCEL KIAA1145 C6orf134 PMAIP1 SAA2 OXTR KPNA1 CP RSNL2 PLSCR1 C5 SOX9 SLC35C1 HIST1H2AC TUBE1 NME5 GJA1 AKR1C3 LAMA3 CAV2 ZNF480 NUDT11 NDRG1 GSTA2 GSTA5 Batch vs 24 hrs Fold vs 24 hrs p-value vs 48 hrs Fold 2.074 -1.602 2.333 1.318 -1.066 -1.650 -1.224 1.320 2.498 -1.454 -1.807 -1.077 1.102 -1.451 3.151 -1.042 -1.059 -1.421 -1.087 2.622 -3.665 2.315 -1.549 -1.310 -1.043 12.560 -1.523 1.099 1.165 -1.301 1.197 21.380 -2.003 -1.291 -1.893 1.403 -1.829 0.0428 0.0977 0.0649 0.216 0.653 0.0477 0.269 0.0542 0.0386 0.136 0.253 0.283 0.457 0.0902 0.0312 0.763 0.652 0.0396 0.619 0.0875 0.0266 0.0366 0.246 0.0706 0.797 0.00732 0.238 0.599 0.320 0.209 0.417 0.0127 0.157 0.137 0.0424 0.146 0.185 2.337 -1.445 2.417 1.497 1.081 -1.842 -1.389 1.366 2.164 -1.685 -2.535 -1.195 -1.126 -2.763 2.409 1.281 -1.252 -1.538 1.144 4.018 -3.073 1.881 -2.370 -1.002 -1.272 20.810 -1.969 -1.158 -1.082 -1.987 -1.181 33.250 -1.359 1.163 -2.450 1.324 -2.523 A vs 48 hrs p-value 0.0114 0.0452 0.0217 0.0150 0.264 0.0133 0.0107 0.0490 0.0150 0.0116 0.00742 0.142 0.249 0.00942 0.0367 0.0744 0.0487 0.0242 0.149 0.00607 0.00687 0.0349 0.0180 0.980 0.0768 0.00126 0.0223 0.273 0.282 0.0249 0.384 0.0117 0.0367 0.0174 0.00607 0.0167 0.0188 vs R vs R Fold p-value -1.154 -2.006 3.743 3.853 3.888 -9.601 3.190 4.277 1.483 14.240 -2.473 -3.255 -3.588 -4.869 1.149 -2.664 -2.564 -5.303 3.492 1.441 -1.685 -1.347 -3.941 -3.197 -4.295 14.200 2.966 2.108 -2.202 -2.550 -2.030 31.380 1.827 -2.181 1.324 2.821 1.204 0.0521 0.0162 0.00308 0.00128 0.00764 0.000926 0.00104 0.00269 0.0181 0.000756 0.00854 0.000790 0.00880 0.00400 0.312 0.00383 0.0542 0.00820 0.00880 0.105 0.0146 0.0601 0.000902 0.0125 0.00300 0.000601 0.00824 0.0100 0.00613 0.0163 0.0404 0.00438 0.0178 0.0185 0.0102 0.0352 0.234 Batch B vs 24 hrs Fold vs 24 hrs p-value vs 48 hrs Fold vs 48 hrs p-value 1.531 -1.552 1.999 1.065 1.123 -1.282 1.008 1.369 1.789 -1.267 -1.996 -1.043 1.019 -1.450 1.839 1.206 -1.040 -1.428 1.052 1.705 -2.486 1.387 -1.614 -1.175 -1.506 10.06 -1.452 -1.099 1.097 -1.878 -1.008 11.890 -1.729 -1.181 -1.518 1.664 -1.448 0.0973 0.0666 0.0820 0.643 0.357 0.115 0.966 0.0690 0.0477 0.289 0.0561 0.737 0.932 0.0822 0.112 0.348 0.817 0.0519 0.659 0.0842 0.0519 0.121 0.180 0.491 0.170 0.0513 0.230 0.426 0.563 0.183 0.950 0.0784 0.133 0.429 0.0973 0.0491 0.0930 2.568 -1.495 2.155 1.333 -1.259 -1.126 -1.302 1.091 2.456 -2.086 -2.166 -1.345 -1.200 -1.633 2.286 2.264 1.011 -1.453 -1.013 2.104 -2.003 2.060 -1.699 -1.343 -1.908 15.330 -3.122 -1.036 -1.048 -2.001 -1.268 21.850 -1.621 -1.194 -2.623 1.701 -2.149 0.0251 0.0357 0.0288 0.0761 0.0742 0.180 0.139 0.444 0.0148 0.0624 0.0296 0.0957 0.317 0.0218 0.0362 0.00670 0.888 0.0386 0.898 0.0368 0.0322 0.0207 0.0390 0.196 0.0500 0.00522 0.0218 0.784 0.664 0.0148 0.0538 0.0211 0.0732 0.296 0.0195 0.0270 0.0176 vs R vs R Fold p-value -1.114 -2.632 2.793 3.855 3.951 -6.321 3.592 5.065 1.552 17.49 -2.072 -3.815 -2.682 -2.199 1.350 -1.401 -2.145 -8.293 3.019 -1.256 -1.163 -1.381 -3.629 -2.567 -8.582 13.980 3.609 2.004 -2.088 1.025 -2.705 25.84 2.017 -3.247 1.034 3.607 1.501 0.253 0.0122 0.0324 0.00309 0.0118 0.00175 0.00901 0.00979 0.0292 0.00240 0.0505 0.00901 0.0115 0.00750 0.212 0.0229 0.0510 0.00147 0.0124 0.246 0.173 0.121 0.0188 0.0432 0.00600 0.00289 0.0153 0.0119 0.0224 0.887 0.0147 0.000887 0.0358 0.0150 0.724 0.00194 0.241 Appendix Phalanx Probe ID GeneBank ID PH_hs_0030079 PH_hs_0030089 PH_hs_0030119 PH_hs_0030157 PH_hs_0030211 PH_hs_0030239 PH_hs_0030259 PH_hs_0030302 PH_hs_0030600 PH_hs_0030754 PH_hs_0030871 PH_hs_0030881 PH_hs_0030898 PH_hs_0030903 PH_hs_0030926 PH_hs_0031064 PH_hs_0031078 PH_hs_0031089 PH_hs_0031096 PH_hs_0031238 PH_hs_0031245 PH_hs_0031365 PH_hs_0031396 PH_hs_0031496 PH_hs_0031510 PH_hs_0031568 PH_hs_0031572 PH_hs_0031600 PH_hs_0031608 PH_hs_0031658 PH_hs_0031712 PH_hs_0031749 PH_hs_0031870 PH_hs_0031884 PH_hs_0031932 PH_hs_0032059 PH_hs_0032109 NM_018393 XM_378178 NM_020129 NM_207387 NM_002986 NM_030913 NM_002925 NM_001683 NM_003633 NM_198147 NM_003088 NM_002237 NM_003116 NM_014474 NM_024605 NM_013253 NM_012168 NM_015385 NM_000067 NM_002264 NM_005434 NM_004566 Entrez Gene Name NM_019111 NM_018357 NM_004815 HLA-DRA FLJ11196 PARG1 NM_001332 NM_005504 NM_005338 CTNND2 BCAT1 HIP1 NM_000187 NM_005130 NM_002309 NM_032932 NM_012121 NM_015892 HGD FGFBP1 LIF RAB11FIP4 CDC42EP4 GALNAC4S -6ST FLJ11336 MGC9913 LGALS14 FLJ35696 CCL11 SEMA6C RGS10 ATP2B2 ENC1 LOC116236 FSCN1 KCNG1 SPAG4 SMPDL3B ARHGAP10 RIG FBXO2 SORBS1 CA2 KPNA1 BENE PFKFB3 Batch A vs 24 hrs Fold vs 24 hrs p-value vs 48 hrs Fold vs 48 hrs p-value vs R vs R Fold p-value 1.253 -1.962 1.311 -1.347 2.689 1.258 1.516 1.240 -2.259 2.666 -1.520 -1.318 -1.785 1.116 -1.062 0.196 0.0383 0.243 0.205 0.106 0.147 0.0497 0.231 0.0548 0.0696 0.0434 0.395 0.0126 0.428 0.573 1.109 -1.355 2.338 -2.022 3.338 -1.142 1.897 1.021 -2.300 3.596 -1.886 -1.754 -2.104 -1.076 1.569 0.269 0.0324 0.0402 0.0193 0.0640 0.204 0.0114 0.471 0.00696 0.0135 0.0131 0.0936 0.0159 0.527 0.0223 -2.537 2.164 -1.375 -1.513 1.498 -2.865 -2.702 -3.509 -2.704 1.925 3.020 3.153 -2.379 -2.064 2.583 -1.053 -1.279 -3.614 1.561 -1.792 -1.176 -1.328 -3.611 -1.391 1.155 1.402 1.268 1.214 -1.382 1.032 1.314 1.603 1.353 -2.111 1.165 1.123 -1.087 0.784 0.233 0.0611 0.125 0.0567 0.101 0.193 0.0193 0.0408 0.503 0.0749 0.133 0.313 0.148 0.804 0.291 0.0523 0.129 0.0344 0.231 0.213 0.442 -1.397 -1.030 -5.705 1.680 -2.287 -1.095 -1.075 -3.663 -2.776 1.191 1.823 1.710 1.529 -1.402 1.061 1.877 3.340 1.122 -2.576 -1.172 -1.298 -1.282 0.0297 0.792 0.00789 0.0204 0.0127 0.223 0.465 0.0116 0.0143 0.194 0.0228 0.0119 0.0230 0.103 0.151 0.0343 0.00371 0.354 0.0143 0.138 0.0707 0.0975 2.190 -2.026 -3.045 -2.083 -12.21 -2.441 -3.078 -9.902 1.044 2.135 -2.171 -6.467 2.301 -2.420 2.795 -2.124 1.966 -4.333 -1.252 -3.475 3.210 2.845 Batch B vs 24 hrs Fold vs 24 hrs p-value vs 48 hrs Fold vs 48 hrs p-value vs R vs R Fold p-value 0.00406 0.00475 0.108 0.0574 0.204 0.00705 0.0219 0.0105 0.000790 0.0186 0.00933 0.0149 0.0153 0.0136 0.0174 1.048 -1.230 1.445 -1.172 2.022 -1.047 1.216 -1.008 -1.709 2.258 -1.335 -1.066 -1.991 -1.219 -1.035 0.539 0.0962 0.120 0.581 0.0879 0.731 0.388 0.845 0.0822 0.101 0.0561 0.808 0.0561 0.276 0.908 -1.256 -1.318 2.631 -2.233 2.903 -1.083 1.166 1.364 -1.684 3.139 -1.969 -1.230 -2.428 -1.062 1.172 0.0386 0.0326 0.0155 0.0377 0.039 0.414 0.355 0.0432 0.0550 0.0545 0.00670 0.335 0.0175 0.547 0.437 -3.891 2.034 -1.146 -1.052 1.027 -2.970 -2.441 -2.518 -2.449 1.755 3.506 3.086 -2.265 -2.088 2.065 0.00849 0.0249 0.236 0.739 0.946 0.0126 0.0355 0.0295 0.00945 0.0788 0.000887 0.0374 0.0819 0.0132 0.0545 0.00622 0.00772 0.00645 0.00697 0.00229 0.00670 0.00935 0.00292 0.462 0.0141 0.0139 0.00726 0.00446 0.0113 0.00109 0.0298 0.0331 0.00438 0.0450 0.00763 0.00124 0.00940 -1.313 -1.190 -2.712 1.359 -1.357 -1.165 -1.251 -2.786 -1.595 1.078 1.441 1.522 1.164 -1.241 -1.029 -1.097 1.553 1.290 -2.926 1.014 1.318 1.018 0.304 0.223 0.0173 0.193 0.393 0.271 0.304 0.0820 0.113 0.403 0.216 0.0415 0.233 0.269 0.692 0.485 0.156 0.214 0.0165 0.782 0.126 0.937 -1.308 -1.007 -5.202 1.941 -3.337 -1.117 -1.644 -2.409 -2.180 1.331 1.496 2.489 1.456 -1.161 -1.009 1.376 2.086 1.294 -2.120 1.195 1.249 -1.226 0.1480 0.933 0.0165 0.0301 0.0742 0.167 0.0591 0.0101 0.0141 0.148 0.0681 0.0133 0.0166 0.200 0.885 0.0580 0.0323 0.107 0.0113 0.0900 0.0386 0.225 2.328 -2.226 -5.014 -2.243 -13.62 -3.071 -3.901 -11.360 1.326 2.359 -3.317 -4.188 2.200 -2.250 2.089 -2.806 1.401 -3.026 -1.094 -2.476 5.507 3.227 0.0200 0.0821 0.0112 0.0199 0.000887 0.0132 0.00964 0.000887 0.0337 0.0198 0.00945 0.00151 0.00286 0.0150 0.0119 0.00455 0.0913 0.0199 0.0908 0.0124 0.000887 0.0149 Appendix Phalanx Probe ID PH_hs_0032238 PH_hs_0032260 PH_hs_0032264 PH_hs_0032279 PH_hs_0032346 PH_hs_0032385 PH_hs_0032398 PH_hs_0032470 PH_hs_0032478 PH_hs_0032525 PH_hs_0032565 PH_hs_0032566 PH_hs_0032595 PH_hs_0032710 PH_hs_0032764 PH_hs_0032872 PH_hs_0032879 PH_hs_0032897 PH_hs_0032959 PH_hs_0032990 PH_hs_0033042 PH_hs_0033092 PH_hs_0033096 PH_hs_0033101 PH_hs_0033119 PH_hs_0033196 PH_hs_0033323 PH_hs_0033367 PH_hs_0033374 PH_hs_0033390 PH_hs_0033480 PH_hs_0033599 PH_hs_0033908 PH_hs_0034019 PH_hs_0034059 PH_hs_0034096 PH_hs_0034256 GeneBank ID NM_152305 NM_052942 NM_003530 NM_201535 NM_152282 NM_005969 NM_006952 XM_292021 NM_005574 NM_133455 NM_000699 NM_014431 NM_000610 NM_018476 NM_033445 NM_000900 NR_001296 NM_003872 NM_021034 XM_370724 NM_015286 NM_002510 NM_002037 NM_004083 XM_171078 NM_005823 NM_006271 NM_021199 NM_002771 NM_000690 NM_003613 XM_371429 NM_003681 NM_030758 NM_033069 XM_379623 XM_211090 Entrez Gene Name MDS010 GBP5 HIST1H3D NDRG2 ACPL2 NAP1L4 UPK1B LOC341346 LMO2 EMID1 AMY2A KIAA1274 CD44 BEX1 HIST3H2A MGP PRSS2 NRP2 IFITM3 C13orf21 DMN GPNMB FYN DDIT3 LOC255324 MSLN S100A1 SQRDL PRSS3 ALDH2 CILP KIAA1666 PDXK OSBP2 C6orf114 LOC401492 LOC283587 Batch vs 24 hrs Fold vs 24 hrs p-value vs 48 hrs Fold -1.031 1.374 -1.706 -1.203 -1.146 1.081 -1.363 1.290 -1.625 -1.378 -1.143 -2.242 2.022 1.010 -2.884 -5.607 -1.157 -1.213 -1.273 1.384 2.310 1.298 1.633 2.126 -1.058 -1.362 -1.144 1.456 -1.095 1.948 -2.919 1.579 1.238 -1.718 -1.769 -1.082 -1.214 0.773 0.0899 0.0431 0.248 0.179 0.573 0.0447 0.111 0.0746 0.332 0.706 0.0570 0.158 0.878 0.0436 0.0298 0.491 0.393 0.142 0.0687 0.0961 0.0703 0.0772 0.0855 0.754 0.179 0.483 0.250 0.516 0.0875 0.0245 0.157 0.0686 0.182 0.244 0.478 0.380 -1.469 1.522 -2.177 -1.146 -1.649 -1.404 -3.571 1.335 -1.560 -1.000 -1.027 -1.875 1.642 1.109 -2.589 -15.120 -1.060 -1.636 1.008 1.415 1.941 1.736 1.874 3.928 1.010 -1.235 -1.261 1.448 -1.220 2.511 -3.614 2.684 1.474 -1.853 -2.409 -1.294 1.041 A vs 48 hrs p-value 0.0263 0.0136 0.0179 0.132 0.0256 0.105 0.00468 0.0243 0.00650 0.999 0.801 0.0268 0.0129 0.199 0.0126 0.000692 0.665 0.0537 0.934 0.0519 0.00607 0.0349 0.0525 0.00607 0.819 0.0548 0.235 0.0366 0.145 0.0105 0.0074 0.0235 0.0368 0.0127 0.0207 0.0796 0.813 vs R vs R Fold p-value -3.329 -2.844 -1.497 2.557 -7.768 -3.825 1.629 13.170 4.586 -3.923 -2.201 -1.783 3.059 -2.738 -2.174 2.268 -3.247 5.176 -2.307 -2.108 4.558 2.574 -2.369 1.286 3.595 -6.842 2.885 3.882 -3.109 1.348 2.190 1.870 2.454 4.144 1.093 -4.782 3.508 0.00609 0.000590 0.0347 0.00583 0.0110 0.00444 0.00639 0.000651 0.00101 0.0133 0.00755 0.0199 0.00609 0.00202 0.00318 0.00152 0.00732 0.00313 0.00863 0.00726 0.000902 0.00710 0.0155 0.0468 0.00494 0.00301 0.0219 0.00333 0.0100 0.0189 0.0171 0.0605 0.00541 0.00611 0.119 0.00308 0.0189 Batch B vs 24 hrs Fold vs 24 hrs p-value vs 48 hrs Fold vs 48 hrs p-value -1.347 1.432 -1.520 -1.188 -1.178 -1.026 -1.658 1.273 -1.540 -1.623 -1.768 -2.026 1.295 -1.052 -2.086 -2.930 -1.045 -1.125 -1.176 1.207 1.420 1.252 1.164 2.309 1.129 -1.140 -1.276 1.187 -1.095 1.943 -1.869 1.253 1.328 -2.252 -1.646 -1.145 1.274 0.153 0.120 0.317 0.195 0.144 0.877 0.084 0.0519 0.108 0.0561 0.211 0.130 0.314 0.692 0.0561 0.0196 0.934 0.667 0.268 0.271 0.205 0.202 0.282 0.0519 0.428 0.144 0.0939 0.271 0.594 0.0384 0.0230 0.432 0.205 0.105 0.180 0.159 0.563 -1.123 2.321 -2.006 -1.014 1.005 1.149 -3.105 1.250 -1.244 -1.336 -2.121 -1.890 1.327 -1.009 -1.886 -13.840 -1.231 -1.557 1.042 1.145 1.493 1.853 2.201 3.794 1.317 -1.150 -1.063 1.129 -1.172 2.665 -1.943 2.150 1.568 -3.294 -2.717 -1.136 1.017 0.0694 0.0113 0.0071 0.852 0.950 0.0900 0.00942 0.0560 0.136 0.102 0.0900 0.0155 0.0824 0.776 0.0291 0.00334 0.569 0.150 0.561 0.353 0.0304 0.0443 0.0176 0.0214 0.0629 0.0888 0.450 0.0717 0.274 0.0184 0.0260 0.0176 0.0271 0.0433 0.0293 0.186 0.962 vs R vs R Fold p-value -2.711 -1.876 -1.147 2.006 -4.322 -2.215 1.543 11.48 6.057 -4.347 -4.670 -2.014 2.214 -3.123 -1.545 2.129 -3.620 5.435 -2.621 -2.180 2.572 3.372 -1.926 1.073 2.702 -4.694 2.911 4.072 -4.105 1.344 2.746 1.497 2.198 2.955 1.068 -3.565 6.182 0.0434 0.0249 0.190 0.00955 0.0198 0.0254 0.0139 0.000767 0.0124 0.0232 0.0200 0.0396 0.0677 0.0153 0.0345 0.00831 0.0915 0.0201 0.00589 0.0458 0.0786 0.00676 0.148 0.449 0.0119 0.0167 0.00556 0.00719 0.0197 0.0279 0.00526 0.136 0.00359 0.0243 0.692 0.0438 0.0294 Appendix Phalanx Probe ID PH_hs_0034360 PH_hs_0034471 GeneBank ID PH_hs_0034684 PH_hs_0034753 PH_hs_0035407 PH_hs_0035435 PH_hs_0035466 PH_hs_0035585 PH_hs_0035694 PH_hs_0035772 PH_hs_0035781 PH_hs_0035830 PH_hs_0035877 PH_hs_0035912 PH_hs_0035989 PH_hs_0036005 PH_hs_0036058 PH_hs_0036148 PH_hs_0036211 PH_hs_0036464 PH_hs_0036468 PH_hs_0036576 XM_371141 NM_001004 441 NM_003518 XM_498675 NM_024610 NM_021194 NM_003739 NM_052813 NM_152663 NM_002982 NM_002276 XM_047499 NM_138373 XM_498994 NM_005241 NM_003153 NM_000598 XM_044166 NM_003983 AK096819 AK096267 BC028572 PH_hs_0036714 PH_hs_0036776 PH_hs_0036845 PH_hs_0037071 PH_hs_0037182 PH_hs_0037318 PH_hs_0037434 PH_hs_0037781 PH_hs_0037802 PH_hs_0037912 PH_hs_0037948 PH_hs_0038086 PH_hs_0038111 PH_hs_0038263 PH_hs_0038290 AK123310 AK097245 BC040486 CR593560 AF131784 BG354579 AK125888 NM_016577 BX640888 AK124907 AK091102 AL355708 AK098422 BC022980 AB028952 Entrez Gene Name Batch A vs 24 hrs Fold vs 24 hrs p-value vs 48 hrs Fold vs 48 hrs p-value vs R vs R Fold p-value LOC388508 DP58 1.298 -1.280 0.217 0.0283 1.284 -1.745 0.138 0.0193 2.731 -3.797 HIST1H2BG LOC440449 HSPBAP1 SLC30A1 AKR1C3 CARD9 RALGPS2 CCL2 KRT19 LOC149603 MYADM LOC441062 EVI1 STAT6 IGFBP3 LOC92312 SLC7A6 SLC2A9 LOC90525 DKFZp761A 132 GA17 CLC ZFP90 LOC440934 RAB27B CBX2 FBXO32 RAB6B GPC6 TMOD2 MGC11082 LOC388134 FLJ36031 LOC202451 SYNPO -3.916 -2.238 1.099 2.048 22.34 1.256 2.145 -1.801 -2.453 1.202 1.179 1.378 -1.523 1.209 -2.392 1.013 1.824 -2.220 1.497 1.851 0.0665 0.0312 0.186 0.0383 0.0397 0.434 0.0766 0.0245 0.0720 0.133 0.227 0.199 0.0605 0.245 0.0495 0.922 0.176 0.0447 0.0787 0.179 -3.785 -1.911 -1.006 1.679 35.99 -1.055 2.230 -2.334 -1.905 1.016 1.155 2.046 -1.273 1.234 -4.327 -1.204 1.355 -2.157 1.739 2.301 0.00755 0.00924 0.887 0.0117 0.00607 0.718 0.0387 0.00608 0.0180 0.755 0.154 0.0133 0.0806 0.0807 0.0091 0.0683 0.317 0.0230 0.0338 0.0349 -1.083 1.927 1.065 -1.711 -1.628 -1.048 -1.962 -1.063 1.461 -1.142 2.615 -1.379 1.048 1.500 -1.819 0.623 0.0952 0.657 0.0572 0.235 0.516 0.0829 0.402 0.164 0.698 0.0262 0.0312 0.672 0.0257 0.0611 -2.389 1.756 1.317 -2.132 -2.060 1.051 -3.150 1.644 1.896 -1.001 3.300 -1.144 -1.139 1.852 -2.101 0.289 0.0135 0.034 0.0136 0.0383 0.371 0.00468 0.0126 0.0450 0.995 0.0105 0.103 0.201 0.0228 0.0127 Batch B vs 24 hrs Fold vs 24 hrs p-value vs 48 hrs Fold vs 48 hrs p-value vs R vs R Fold p-value 0.00798 0.00477 1.150 -1.341 0.478 0.186 1.083 -1.369 0.571 0.0280 2.233 -3.439 0.0236 0.00534 -2.815 5.068 -2.761 2.255 29.39 3.524 2.040 -11.470 2.044 -2.146 2.421 6.399 2.593 2.240 1.277 -2.094 2.143 -1.855 -2.033 1.522 0.00821 0.00059 0.00194 0.0109 0.00059 0.0108 0.0319 0.000651 0.00992 0.00647 0.00598 0.00109 0.00394 0.00691 0.127 0.00350 0.0761 0.0295 0.0100 0.0437 -2.389 -1.450 -1.041 1.852 14.23 1.417 1.479 -1.318 -2.145 1.305 1.205 1.682 -1.764 1.395 -2.187 1.104 1.358 -1.949 1.314 1.704 0.0519 0.0666 0.802 0.0934 0.0519 0.255 0.115 0.162 0.140 0.138 0.493 0.185 0.153 0.281 0.0718 0.233 0.161 0.0728 0.165 0.133 -2.486 -1.595 1.105 1.570 23.250 1.080 1.684 -2.328 -2.405 2.079 1.856 1.986 -1.767 1.678 -3.395 -1.158 1.435 -2.168 1.287 2.251 0.0235 0.0195 0.110 0.0552 0.00942 0.654 0.0300 0.0148 0.0352 0.0148 0.0777 0.0413 0.0817 0.106 0.0155 0.0140 0.0587 0.0238 0.237 0.0285 -2.221 4.997 -2.284 2.615 19.950 3.451 2.627 -18.140 1.615 1.105 2.717 6.676 2.149 2.311 1.618 -2.431 2.558 -1.518 -2.484 2.020 0.0445 0.000887 0.00324 0.0151 0.00324 0.0154 0.0255 0.000887 0.0657 0.249 0.0519 0.00726 0.0280 0.0413 0.0704 0.0813 0.0198 0.0485 0.0742 0.0460 2.141 3.790 -2.214 1.000 1.307 -2.051 -1.383 -2.169 -6.335 -4.233 1.188 -2.638 -2.754 3.447 -2.540 0.0200 0.00598 0.00726 0.996 0.0375 0.00331 0.0457 0.0470 0.0148 0.00675 0.0945 0.00209 0.00398 0.00263 0.00978 -1.284 2.307 1.037 -1.482 -1.798 -1.050 -1.595 -1.369 1.009 -1.973 2.277 -1.104 -1.022 1.269 -1.626 0.354 0.0519 0.830 0.153 0.221 0.454 0.101 0.330 0.956 0.134 0.0519 0.205 0.922 0.263 0.0906 -2.180 1.650 1.255 -2.178 -2.233 1.093 -2.940 -1.092 1.171 -2.531 2.755 -1.028 -1.057 1.513 -1.773 0.0250 0.0282 0.0757 0.0205 0.0845 0.159 0.0385 0.632 0.118 0.0454 0.0127 0.677 0.662 0.0477 0.0509 1.231 2.951 -2.439 -1.015 1.330 -2.130 -1.077 -4.515 -10.740 -5.951 1.267 -2.642 -2.352 2.682 -2.239 0.138 0.00365 0.00584 0.901 0.329 0.00419 0.656 0.0206 0.00556 0.0125 0.281 0.00359 0.0251 0.0226 0.0124 Appendix Phalanx Probe ID PH_hs_0038537 PH_hs_0038844 PH_hs_0038876 PH_hs_0038883 PH_hs_0038919 PH_hs_0038991 PH_hs_0039790 PH_hs_0040130 PH_hs_0040288 PH_hs_0040625 PH_hs_0040710 PH_hs_0040800 PH_hs_0040823 PH_hs_0040930 PH_hs_0041072 GeneBank ID XM_375747 XM_499353 NM_005953 BX649128 BC030694 NM_021123 BC042436 NM_002958 NM_005165 NM_203481 NM_002053 NM_012338 AK091558 NM_001874 NM_016577 Entrez Gene Name LOC400759 LOC401330 LOC441019 SESN3 MYCL1 GAGE7 GPCR5A RYK ALDOC MGC70870 GBP1 TM4SF12 LIPA CPM RAB6B Batch vs 24 hrs Fold vs 24 hrs p-value vs 48 hrs Fold -1.416 -1.305 3.066 -2.321 -1.835 1.029 1.551 1.086 -1.037 1.107 -1.378 -2.381 1.313 -3.562 1.229 0.183 0.254 0.0257 0.142 0.0953 0.867 0.0209 0.374 0.854 0.272 0.190 0.0629 0.520 0.0665 0.270 -2.372 -1.650 3.649 -1.817 -1.975 1.002 1.691 -1.349 -1.307 -1.729 -2.983 -3.318 2.570 -8.712 1.138 A vs 48 hrs p-value 0.0135 0.0116 0.0105 0.0162 0.0271 0.977 0.0333 0.0141 0.0886 0.0292 0.00607 0.00854 0.0813 0.0327 0.359 vs R vs R Fold p-value -4.986 3.524 1.370 -1.061 -2.139 8.032 4.503 -5.643 2.223 -4.082 -4.166 6.694 3.075 -1.130 -2.985 0.00459 0.00672 0.0349 0.539 0.0190 0.000902 0.00824 0.00059 0.00730 0.00170 0.00350 0.00444 0.0480 0.0546 0.0171 Batch B vs 24 hrs Fold vs 24 hrs p-value vs 48 hrs Fold vs 48 hrs p-value -1.638 -1.126 2.759 -2.299 -2.278 -1.027 1.449 -1.058 -1.267 -1.216 -1.712 -2.413 2.211 -3.466 -1.075 0.222 0.176 0.0862 0.0912 0.0718 0.882 0.233 0.607 0.309 0.219 0.0891 0.0666 0.257 0.0520 0.718 -2.232 1.010 3.348 -2.254 -1.776 -1.102 1.569 1.216 -1.032 1.291 -1.230 -4.249 3.139 -3.752 1.212 0.101 0.876 0.0418 0.0355 0.0287 0.425 0.113 0.0686 0.806 0.0527 0.0301 0.00670 0.104 0.0101 0.0816 vs R vs R Fold p-value -3.321 4.791 1.183 -1.242 -2.297 6.986 5.000 -2.642 3.396 -2.662 -3.751 4.149 3.965 -1.103 -2.696 0.0121 0.00251 0.296 0.210 0.0466 0.0132 0.0234 0.0132 0.0115 0.255 0.00212 0.00794 0.0778 0.291 0.0182 Appendix Phalanx Probe ID Appendix Phalanx Probe ID GeneBank ID Entrez Gene Name Average Fold Change# PH_hs_0035466 PH_hs_0027536 PH_hs_0005148 PH_hs_0005671 PH_hs_0004352 PH_hs_0011943 PH_hs_0032470 PH_hs_0001558 PH_hs_0011511 PH_hs_0004409 PH_hs_0026808 PH_hs_0024170 PH_hs_0004996 PH_hs_0038991 PH_hs_0019619 PH_hs_0022372 PH_hs_0014156 PH_hs_0035912 PH_hs_0005514 PH_hs_0002314 PH_hs_0005421 PH_hs_0000100 PH_hs_0008826 PH_hs_0004098 PH_hs_0000235 PH_hs_0024398 PH_hs_0040800 PH_hs_0032478 PH_hs_0032897 PH_hs_0000953 PH_hs_0002935 PH_hs_0024092 PH_hs_0025524 PH_hs_0006947 PH_hs_0007104 PH_hs_0011503 PH_hs_0011690 PH_hs_0034753 PH_hs_0026823 PH_hs_0022469 PH_hs_0004577 PH_hs_0034256 PH_hs_0039790 PH_hs_0027323 PH_hs_0005870 PH_hs_0006395 PH_hs_0012806 PH_hs_0032059 PH_hs_0001536 PH_hs_0024961 PH_hs_0026843 PH_hs_0025875 PH_hs_0023764 NM_003739 NM_030754 NM_016352 NM_002317 NM_000591 NM_002133 XM_292021 NM_004753 NM_004751 NM_000689 NM_006512 NM_002272 NM_002110 NM_021123 NM_002964 NM_001275 NM_000930 XM_498994 NM_032717 NM_183240 NM_153362 NM_002164 NM_001445 NM_152673 NM_000575 NM_004207 NM_012338 NM_005574 NM_003872 NM_016267 NM_001741 NM_007129 NM_203447 AK097496 NM_022119 NM_003979 NM_005458 XM_498675 NM_004613 NM_005715 XM_027236 XM_211090 BC042436 NM_024909 NM_032034 NM_020299 NM_005725 NM_005434 NM_007150 NM_001565 NM_024896 NM_002589 NM_002061 AKR1C3* SAA2 CPA4 LOX CD14 HMOX1 LOC341346 DHRS3 GCNT3 ALDH1A1 SAA4 KRT4 HCK GAGE7 S100A8 CHGA PLAT LOC441062 MGC11324 TMEM37 PRSS35 INDO FABP6 MUC20 IL1A SLC16A3 TM4SF12 LMO2 NRP2 VGLL1 CALCA ZIC2 DOCK8 LOC283352 PRSS22 GPCR5A GPR51 LOC440449 TGM2 UST TTC9 LOC283587 GPCR5A C6orf134 SLC4A11 AKR1B10 TSPAN-2 BENE ZNF185 CXCL10 KIAA1815 PCDH7 GCLM 24.670 15.865 13.980 13.740 13.490 12.550 12.325 12.220 11.485 10.365 10.003 9.748 7.912 7.509 7.344 7.201 7.109 6.538 6.399 5.971 5.923 5.826 5.730 5.605 5.533 5.509 5.422 5.322 5.306 5.299 5.297 5.170 5.091 5.065 5.061 5.058 5.050 5.033 4.964 4.897 4.883 4.845 4.752 4.671 4.641 4.486 4.374 4.359 4.353 4.315 4.311 4.220 4.170 PH_hs_0000282 NM_004447 EPS8 4.166 # Summary of Function Electron transport Histone acetylation Signal transduction Apoptosis; immune response Oxidative Stress response Cellular metabolism Cellular metabolism Cellular metabolism Lipid transporter Cytoskeleton; cell communication Kinase Calcium ion binding Calcium ion binding Proteolysis; PDGF signalling Cellular metabolism Ion transporter Proteolysis Metal ion binding Cell proliferation Protein oligomerization Cell growth; apoptosis Anion transporter Metal ion binding Cell differentiation Transcription regulation Cell signalling Cell differentiation GTP and GTPAse binding Proteolysis Signal transduction Signal transduction Cell adhesion; cell signalling Enzyme Signal transduction Anion transporter Cellular metabolism Cell proliferation; cell adhesion Protein binding Cell signalling Proteolysis; metal ion binding Cell adhesion Glutathione metabolism, oxidative stress response Cell signaling; cell proliferation Average fold change represents the mean fold change value obtained from averaging the fold change for Batch A and Batch B * Gene with duplicated probe Appendix Phalanx Probe ID GeneBank ID Entrez Gene Name Average Fold Change# PH_hs_0038844 PH_hs_0002434 PH_hs_0022632 PH_hs_0000458 PH_hs_0000305 PH_hs_0005065 PH_hs_0023550 PH_hs_0016124 PH_hs_0033367 PH_hs_0027214 PH_hs_0025588 PH_hs_0014290 PH_hs_0027200 PH_hs_0026522 PH_hs_0003007 PH_hs_0000598 PH_hs_0001407 PH_hs_0002731 PH_hs_0001390 PH_hs_0006160 PH_hs_0002227 PH_hs_0034019 PH_hs_0006423 PH_hs_0012708 PH_hs_0035585 PH_hs_0019591 PH_hs_0013167 PH_hs_0020084 PH_hs_0036776 XM_499353 BM709175 NM_007361 NM_152523 NM_002425 NM_004695 NM_004665 NM_002231 NM_021199 NM_003843 NM_020453 NM_000611 BC010607 NM_002627 NM_005727 NM_005476 NM_002655 NM_002194 NM_002395 NM_002965 NM_004633 NM_030758 NM_181785 NM_031422 NM_052813 NM_019894 NM_023926 NM_018413 AK097245 LOC401330 HSU79275 NID2 FLJ40432 MMP10 SLC16A5 VNN2 KAI1 SQRDL SCEL ATP10D CD59 MGC18216 PFKP TSPAN-1 GNE PLAG1 INPP1 ME1 S100A9 IL1R2 OSBP2 LOC283537 CHST9 CARD9 TMPRSS4 MTNR1A CHST11 CLC* 4.158 4.132 4.119 4.108 4.036 4.030 3.999 3.996 3.977 3.920 3.893 3.871 3.854 3.834 3.798 3.741 3.693 3.685 3.661 3.643 3.551 3.549 3.515 3.597 3.488 3.479 3.399 3.391 3.371 PH_hs_0029016 PH_hs_0014783 PH_hs_0027162 PH_hs_0030871 PH_hs_0028763 PH_hs_0004694 PH_hs_0000152 PH_hs_0024953 PH_hs_0022374 PH_hs_0033119 PH_hs_0030881 PH_hs_0026357 PH_hs_0010092 PH_hs_0004062 PH_hs_0000006 PH_hs_0038263 PH_hs_0032109 PH_hs_0023411 PH_hs_0007351 PH_hs_0000909 PH_hs_0025826 NM_000227 NM_015894 NM_002394 NM_005130 NM_018389 NM_000877 NM_002118 NM_032466 NM_020169 XM_171078 NM_002309 NM_023938 NM_000149 NM_000474 NM_000952 BC022980 NM_004566 NM_138451 NM_001165 NM_006105 NM_000904 LAMA3 STMN3 SLC3A2 FGFBP1 SLC35C1 IL1R1 HLA-DMB ASPH LXN LOC255324 LIF SARG FUT3 TWIST1 PTAFR LOC202451 PFKFB3 IQCD BIRC3 RAPGEF3 NQO2 3.288 3.278 3.268 3.263 3.256 3.252 3.245 3.241 3.201 3.149 3.119 3.100 3.092 3.092 3.067 3.065 3.036 3.023 3.001 2.996 2.991 PH_hs_0006549 PH_hs_0033092 PH_hs_0003939 PH_hs_0001854 NM_004480 NM_002510 NM_001993 NM_020168 FUT8 GPNMB F3 PAK6 2.974 2.973 2.962 2.949 # Summary of Function Cell adhesion Cell cycle Metalloproteinase; cell signalling Anion transporter Hydrolase Protein binding Metal ion binding; protein binding Cation transporter Immune response Antiapoptosis; insulin receptor signalling Cellular metabolism Cell proliferation Cell adhesion; cell metabolism Metal ion binding Signal transduction Cellular metabolism Cell signalling Immune response Lipid transport Proteolysis Apoptosis; cell signalling Proteolysis Signal transduction Carbohydrate metabolism Apoptosis; cell signaling; cell differentiation Cell migration; cell adhesion Signal transduction Transporter Cell proliferation; signal transduction Transporter Cytokine signaling; immune response Immune response Calcium ion binding Carboxypeptidase inhibitor Cell signalling; immune response Cellular metabolism Cell differentiation Cell signalling Cellular metabolism Glycolysis Antiapoptosis Cell proliferation Oxidative stress response; electron transport Cellular metabolism Cell adhesion; cell proliferation Blood coagulation; immune response Protein phosphorylation Average fold change represents the mean fold change value obtained from averaging the fold change for Batch A and Batch B * Gene with duplicated probe Appendix Phalanx Probe ID GeneBank ID Entrez Gene Name PH_hs_0033323 PH_hs_0009300 PH_hs_0003342 PH_hs_0027093 PH_hs_0025057 PH_hs_0009600 PH_hs_0040288 PH_hs_0003982 PH_hs_0002700 PH_hs_0003822 PH_hs_0000382 PH_hs_0004661 PH_hs_0012389 PH_hs_0004472 PH_hs_0019818 PH_hs_0027041 NM_006271 NM_001236 NM_001248 NM_005704 NM_000350 NM_003857 NM_005165 NM_003227 NM_013370 NM_006557 NM_021147 NM_002961 NM_144590 NM_015158 NM_003662 NM_002423 S100A1 CBR3 ENTPD3 PTPRU ABCA4 GALR2 ALDOC* TFR2 OKL38 DMRT2 UNG2 S100A4 ANKRD22 ANKRD15 PIR MMP7 2.898 2.886 2.868 2.857 2.844 2.825 2.809 2.771 2.756 2.739 2.726 2.724 2.719 2.716 2.692 2.649 PH_hs_0024448 PH_hs_0004629 PH_hs_0001733 PH_hs_0005982 PH_hs_0003767 PH_hs_0027024 NM_003730 NM_002371 NM_001902 NM_005689 NM_023915 NM_000359 RNASET2 MAL CTH ABCB6 GPR87 TGM1 2.589 2.587 2.572 2.569 2.569 2.545 PH_hs_0000249 PH_hs_0004626 NM_002633 NM_002275 PGM1 KRT15 2.537 2.535 PH_hs_0001148 PH_hs_0022370 PH_hs_0020591 PH_hs_0022944 PH_hs_0008291 PH_hs_0024837 PH_hs_0000211 PH_hs_0034360 PH_hs_0007485 PH_hs_0026095 PH_hs_0033480 PH_hs_0006823 PH_hs_0025607 PH_hs_0027088 PH_hs_0031658 PH_hs_0035435 PH_hs_0000440 PH_hs_0027127 PH_hs_0003985 PH_hs_0022999 PH_hs_0020618 PH_hs_0035989 NM_024554 NM_172373 NM_153233 NM_006867 NM_053276 NM_004304 NM_000861 XM_371141 NM_022089 NM_022036 NM_003613 NM_173660 NM_004998 NM_031430 NM_024605 NM_021194 NM_014403 NM_004282 NM_004392 NM_003567 NM_000228 NM_005241 PGBD5 ELF1 FLJ36445 RBPMS VIT ALK HRH1 LOC388508 HSA9947 GPRC5C CILP FLJ33718 MYO1E RILP ARHGAP10 SLC30A1 SIAT7D BAG2 DACH1 BCAR3 LAMB3 EVI1 2.533 2.521 2.508 2.508 2.508 2.501 2.486 2.482 2.480 2.469 2.468 2.463 2.461 2.449 2.442 2.435 2.426 2.420 2.398 2.395 2.389 2.371 PH_hs_0011502 PH_hs_0017058 PH_hs_0006124 PH_hs_0000449 PH_hs_0020456 PH_hs_0005058 NM_003976 NM_145280 NM_003890 NM_006499 NM_138768 NM_003786 ARTN LOC151194 FCGBP LGALS8 MYEOV ABCC3 2.369 2.354 2.348 2.347 2.337 2.336 # Average Fold Change# Summary of Function Cell signalling Cellular metabolism Cellular metabolism Cell adhesion; signal transduction Transporter Signal transduction Cellular metabolism Metal transport Cell growth and differentiation Transcription factor Cell cycle Calcium binding; protein binding Cell cycle Cellular transcription Metalloproteinase; tumor progression and metastasis RNA catabolism Apoptosis; cell differentiation Amino acid synthesis Transporter Signal transduction Protein binding; calcium ion binding Cellular metabolism Cytoskeletal component; cell communication Transcription factor Protein binding; RNA binding Cell signalling Cell signalling; inflammatory response Transporter Signal transduction Nucleoside metabolism Protein binding Calmodulin binding ; nucleotide binding Protein transport Signal transduction Cation transporter Antiapoptosis; protein binding Transcription factor Cell cycle Cell adhesion; protein binding Cell proliferation; transcription regulation Signal transduction Cell adhesion Sugar binding Transporter Average fold change represents the mean fold change value obtained from averaging the fold change for Batch A and Batch B * Gene with duplicated probe Appendix Phalanx Probe ID GeneBank ID Entrez Gene Name Average Fold Change# PH_hs_0019988 PH_hs_0035694 PH_hs_0033908 PH_hs_0005127 PH_hs_0025701 PH_hs_0009153 PH_hs_0012796 PH_hs_0032279 PH_hs_0036005 PH_hs_0031064 PH_hs_0031600 PH_hs_0016000 PH_hs_0031510 PH_hs_0025342 PH_hs_0012041 PH_hs_0005010 PH_hs_0025967 PH_hs_0000788 PH_hs_0025324 PH_hs_0032872 PH_hs_0022977 PH_hs_0001383 PH_hs_0007227 PH_hs_0012825 PH_hs_0024845 PH_hs_0022734 PH_hs_0022539 PH_hs_0002484 PH_hs_0010879 PH_hs_0004398 PH_hs_0023937 PH_hs_0030089 PH_hs_0000490 PH_hs_0007483 PH_hs_0000455 PH_hs_0029204 PH_hs_0003443 PH_hs_0002286 PH_hs_0002304 PH_hs_0025088 PH_hs_0030903 XM_0395153 NM_152663 NM_003681 NM_004598 NM_017842 NM_005923 NM_004925 NM_201535 NM_003153 NM_018393 NM_003116 NM_182920 NM_198147 NM_153365 NM_020467 NM_000120 NM_003937 NM_002005 NM_182729 NM_000900 NM_153811 NM_006332 NM_025045 NM_016354 NM_004631 NM_016339 NM_006384 NM_023935 NM_001835 NM_004105 NM_006120 NM_019111 NM_001262 NM_016240 NM_014294 NM_001233 NM_015187 NM_015464 NM_014112 NM_212474 NM_012121 G2 RALGPS2 PDXK SPOCK FLJ20489 MAP3K5 AQP3 NDRG2 STAT6 FLJ11336 SPAG4 ADAMTS9 LOC116236 FLJ90013 LOC57228 EPHX1 KYNU FES TXNRD1 MGP SLC38A6 IFI30 FLJ22582 SLCO4A1 LRP8 RAPGEFL1 CIB1 C20orf116 CLTCL1 EFEMP1 HLA-DMA HLA-DRA CDKN2C SCARA3 TRAM1 CAV2 KIAA0746 SOSTDC1 TRPS1 FN1 CDC42EP4 2.336 2.334 2.326 2.318 2.312 2.302 2.295 2.282 2.276 2.259 2.251 2.249 2.247 2.242 2.238 2.223 2.206 2.205 2.203 2.199 2.191 2.190 2.189 2.189 2.188 2.169 2.166 2.156 2.126 2.125 2.108 2.099 2.091 2.085 2.083 2.056 1.904 -1.967 -1.969 -2.019 -2.076 PH_hs_0003032 PH_hs_0000076 PH_hs_0037318 PH_hs_0022779 PH_hs_0004982 PH_hs_0032990 PH_hs_0029218 PH_hs_0024164 PH_hs_0025782 PH_hs_0015041 PH_hs_0016017 PH_hs_0004004 PH_hs_0031096 PH_hs_0004265 PH_hs_0001026 PH_hs_0038919 NM_003916 NM_000882 BG354579 NM_017664 NM_004395 XM_370724 NM_144684 XM_031553 NM_001431 NM_023067 NM_182704 NM_002048 NM_207387 NM_023009 NM_006350 BC030694 AP1S2 IL12A CBX2 ANKRD10 DBN1 C13orf21 ZNF480 SR140 EPB41L2 FOXL2 SELV GAS1 FLJ35696 MARCKSL1 FST MYCL1 -2.079 -2.089 -2.091 -2.117 -2.124 -2.144 -2.145 -2.147 -2.148 -2.149 -2.153 -2.161 -2.163 -2.179 -2.190 -2.218 # Summary of Function Signal transduction Metal ion binding Cell proliferation; cell adhesion Apoptosis; Mapkkk signalling Transporter Cell differentiation Apoptosis; signal transduction Cytoskeletal component Proteolysis Detoxification Cellular metabolism Cell proliferation; cell signalling Oxidative stress response Cell differentiation; ECM component Immune response Transporter Signal transduction Signal transduction Apoptosis; DNA damage response Protein binding Immune response Immune response Cell cycle Oxidative stress response Protein transport Cell proliferation; protein binding KIAA0746 protein Sclerostin domain containing Trichorhinophalangeal syndrome I Cell signalling; cell adhesion Regulation of cell shape; signal transduction; protein binding Protein transport Chromatin assembly Cell differentiation Transcription regulation Nucleotide binding Cytosekleton organisation Apoptosis; cell differentiation Oxidative stress response Cell cycle arrest Calmodulin binding Cell differentiation; cell signalling Transcription regulation Average fold change represents the mean fold change value obtained from averaging the fold change for Batch A and Batch B * Gene with duplicated probe Appendix Phalanx Probe ID GeneBank ID Entrez Gene Name PH_hs_0021087 PH_hs_0005744 PH_hs_0002532 PH_hs_0023568 PH_hs_0019710 PH_hs_0000928 PH_hs_0002730 PH_hs_0026765 PH_hs_0005789 PH_hs_0012818 PH_hs_0027161 PH_hs_0036845 PH_hs_0031608 PH_hs_0006015 PH_hs_0015559 PH_hs_0010267 PH_hs_0032260 PH_hs_0014044 PH_hs_0001244 PH_hs_0029418 PH_hs_0025212 PH_hs_0003705 PH_hs_0017206 PH_hs_0038290 PH_hs_0010095 PH_hs_0004394 PH_hs_0020829 PH_hs_0012283 PH_hs_0014077 PH_hs_0015584 PH_hs_0002958 NM_207436 NM_032438 NM_024610 NM_015570 NM_001849 NM_031442 NM_173672 NM_016356 NM_007152 NM_023926 NM_015149 BC040486 NM_014474 NM_006963 NM_207376 NM_173549 NM_052942 NM_017581 XM_084578 NM_018159 NM_015993 NM_152332 NM_003586 AB028952 NM_003238 NM_004364 NM_018494 NM_152742 NM_000944 NM_019558 AK055969 PH_hs_0002058 PH_hs_0032959 PH_hs_0031712 PH_hs_0025081 PH_hs_0024009 PH_hs_0019618 PH_hs_0004817 PH_hs_0014556 PH_hs_0024008 PH_hs_0009662 PH_hs_0022310 PH_hs_0010138 PH_hs_0010138 PH_hs_0034684 PH_hs_0035407 PH_hs_0025869 PH_hs_0038111 PH_hs_0023636 PH_hs_0025139 PH_hs_0030259 PH_hs_0013274 PH_hs_0001684 NM_030817 NM_021034 NM_013253 NM_016831 NM_002604 CR602569 NM_022443 NM_032383 NM_182487 XM_499250 NM_004390 AK023631 AK023631 NM_003518 NM_024610 NM_014883 AK098422 NM_001751 NM_001449 NM_005504 NM_016354 NM_012305 FLJ42957 L3MBTL3 HSPBAP1* AUTS2 COL6A2 TM4SF10 PPIL6 DCDC2 ZNF195 FLJ12895 RGL1 ZFP90 SMPDL3B ZNF22 LOC387882 FLJ39553 GBP5 CHRNA9 PPFIBP2 NUDT11 TM4SF11 MTAC2D1 DOC2A SYNPO TGFB2 CEBPA LRDD GPC2 PPP3CA HOXD8 DKFZP434F03 18 IFITM3 RIG PER3 PDE7A MLF1 HPS3 OLFML2A LFNG CTSH HIST1H2BG HSPBAP1* FAM13A1 FLJ36031 CARS FHL1 BCAT1 TRPC1 AP2A2 # Average Fold Change# -2.224 -2.233 -2.265 -2.267 -2.272 -2.272 -2.281 -2.290 -2.301 -2.312 -2.319 -2.327 -2.335 -2.343 -2.345 -2.358 -2.360 -2.362 -2.364 -2.368 -2.371 -2.379 -2.384 -2.389 -2.390 -2.396 -2.419 -2.421 -2.421 -2.438 -2.452 -2.458 -2.464 -2.465 -2.473 -2.478 -2.481 -2.481 -2.493 -2.496 -2.503 -2.511 -2.517 -2.517 -2.518 -2.523 -2.533 -2.553 -2.554 -2.568 -2.572 -2.584 -2.610 Summary of Function Transcription regulation HSPB associated protein Endopeptidase inhibitor Extracellular matrix component Protein folding Cell signalling Transcription regulation Transcription regulation Signal transduction Transcription regulation Cellular metabolism Transcription regulation Adaptor molecule; immunity Transporter Adaptor protein Signal transduction Transporter Transporter Cytoskeleton organisation Cell growth; cell death Transcription factor Apoptosis; signal transuction Cell cycle Transcription regulation ‐  Immune response Signal transduction Transcription; signal transduction ‐  Cell cycle arrest; cell differentiation Proteolysis ‐  ‐  Protein folding and unfolding Signal transduction Metal ion binding Cell growth; cell differentiation Cell cycle Transporter Adaptor protein Average fold change represents the mean fold change value obtained from averaging the fold change for Batch A and Batch B * Gene with duplicated probe Appendix Phalanx Probe ID GeneBank ID Entrez Gene Name PH_hs_0022739 PH_hs_0005182 PH_hs_0038086 PH_hs_0003912 PH_hs_0024713 PH_hs_0019583 PH_hs_0004441 PH_hs_0031568 PH_hs_0000678 PH_hs_0031245 PH_hs_0020300 PH_hs_0014431 PH_hs_0012930 PH_hs_0025862 PH_hs_0001061 PH_hs_0005123 PH_hs_0041072 PH_hs_0004307 PH_hs_0010944 PH_hs_0024758 PH_hs_0025581 PH_hs_0028942 PH_hs_0025799 PH_hs_0005972 PH_hs_0030239 PH_hs_0022409 PH_hs_0032710 PH_hs_0003660 PH_hs_0026589 PH_hs_0026605 PH_hs_0024930 PH_hs_0002640 PH_hs_0025004 PH_hs_0031932 PH_hs_0007344 PH_hs_0022138 PH_hs_0030302 PH_hs_0032238 PH_hs_0032385 XM_114303 NM_021809 AL355708 AK127315 NM_001846 NM_024430 NM_000345 NM_003088 NM_030792 NM_030913 NM_004385 NM_014583 NM_004925 NM_002065 XM_372774 NM_032512 NM_016577 NM_006026 NM_013396 NM_003034 NM_001845 NM_003551 NM_001744 NM_145244 NM_001332 NM_032867 NM_018476 NM_003149 NM_145909 NM_006317 NM_000132 NM_004093 NM_014234 NM_002264 NM_018431 NM_014548 NM_005338 NM_152305 NM_005969 PH_hs_0000414 PH_hs_0003661 PH_hs_0025184 PH_hs_0016489 PH_hs_0024827 PH_hs_0027908 PH_hs_0007590 PH_hs_0025269 PH_hs_0011706 PH_hs_0020408 PH_hs_0010369 PH_hs_0000554 PH_hs_0037781 PH_hs_0005930 NM_015544 NM_021992 NM_024907 NM_138287 NM_016105 NM_002264 NM_001195 NM_013343 NM_005467 XM_086879 AK091332 NM_006108 NM_016577 NM_014141 FRMD4B TGIF2 LOC388134 COL4A2 PSTPIP2 SNCA FSCN1 PP1665 SEMA6C CSPG2 LMCD1 LTBP1 GLUL DJ159A19.3 PDZK4 RAB6B H1FX USP25 SIAT8A COL4A1 NME5 CAMK4 DDIT4L CTNND2 FLJ14966 BEX1* STAC ZNF323 BASP1 F8 EFNB2 HSD17B8 KPNA1 DOK5 TMOD2 HIP1 MDS010 NAP1L4 DKFZP564K19 64 TMSNB FBXO17 DTX3L FKBP7 KPNA1* BFSP1 LOH3CR2A NAALAD2 LOC150371 SPON1 RAB6B CNTNAP2 # Average Fold Change# -2.619 -2.632 -2.640 -2.644 -2.682 -2.685 -2.718 -2.744 -2.748 -2.756 -2.760 -2.768 -2.781 -2.788 -2.796 -2.821 -2.841 -2.861 -2.864 -2.868 -2.880 -2.882 -2.893 -2.904 -2.918 -2.927 -2.931 -2.931 -2.944 -2.952 -2.959 -2.962 -2.975 -2.976 -2.981 -2.984 -3.014 -3.020 -3.020 -3.031 -3.069 -3.074 -3.082 -3.103 -3.135 -3.144 -3.150 -3.190 -3.207 -3.218 -3.299 -3.342 -3.429 Summary of Function Protein binding Transcription regulation ‐  Extracellular matrix component Antiapoptosis Cell proliferation; cytoskeleton Cellular metabolism Cell differentiation Cell adhesion Transcription regulation TGFb singalling Cellular metabolism Protein binding Signal transduction; vesicle transport Chromosone organisation Proteolysis Metabolism; cell proliferation; Extracellular matrix component Oxidative stress response Signal transduction Signal transduction; transcription Brain expressed, X-linked Cell signalling Transcription regulation Blood coagulation; cell adhesion Cell differentiation; cell signalling Cellular metabolism Karyopherin alpha Mapkkk signalling cascade Tropomodulin (neuronal) Apoptosis Protein binding Cytoskeleton organisation Protein degradation Protein binding; metal ion binding Protein transport; protein binding Cytoskeleton; protein binding Peptidase ‐  Cell adhesion Signal transduction; vesicle transport Cell adhesion Average fold change represents the mean fold change value obtained from averaging the fold change for Batch A and Batch B * Gene with duplicated probe Appendix Phalanx Probe ID PH_hs_0016853 PH_hs_0032565 PH_hs_0024015 PH_hs_0015577 PH_hs_0031365 PH_hs_0028098 PH_hs_0026600 PH_hs_0024014 PH_hs_0024094 PH_hs_0024812 PH_hs_0002179 PH_hs_0033374 PH_hs_0034471 PH_hs_0031870 PH_hs_0011493 PH_hs_0001811 PH_hs_0000691 PH_hs_0022465 PH_hs_0008975 PH_hs_0020156 PH_hs_0025293 PH_hs_0022589 PH_hs_0009360 PH_hs_0025272 PH_hs_0040710 PH_hs_0013301 PH_hs_0031089 PH_hs_0000202 PH_hs_0010807 PH_hs_0032525 PH_hs_0040130 PH_hs_0038537 PH_hs_0034096 PH_hs_0009841 PH_hs_0000763 PH_hs_0000085 PH_hs_0022233 PH_hs_0005961 PH_hs_0023602 PH_hs_0026578 PH_hs_0003766 PH_hs_0003988 PH_hs_0020546 PH_hs_0005583 PH_hs_0025250 PH_hs_0003752 PH_hs_0000702 PH_hs_0020111 PH_hs_0008565 PH_hs_0023962 PH_hs_0026662 PH_hs_0001688 PH_hs_0022217 PH_hs_0037912 # GeneBank ID NM_012219 NM_000699 AL832164 NM_018640 NM_002925 NM_000096 NM_006500 NM_003199 NM_145035 NM_052941 NM_020925 NM_002771 NM_0010044 41 NM_015385 NM_001839 NM_004086 XM_376018 NM_031458 BG546536 NM_000424 NM_006097 NM_003986 NM_021643 NM_025080 NM_002053 NM_006580 NM_020129 NM_001552 NM_001661 NM_133455 NM_002958 XM_375747 XM_379623 NM_007064 NM_022912 NM_023105 NM_022454 NM_031455 NM_178012 NM_005965 NM_145307 NM_000313 NM_021219 NM_000044 NM_003108 NM_001448 NM_015529 NM_000597 NM_004429 NM_052832 NM_001955 XM_378360 NM_003317 AK124907 Entrez Gene Name Average Fold Change# MRAS AMY2A LOC283666 LMO3 RGS10 CP MCAM TCF4 ADMP GBP4 KIAA1573 PRSS3 -3.436 -3.436 -3.446 -3.449 -3.489 -3.534 -3.548 -3.567 -3.583 -3.594 -3.600 -3.607 DP58 SORBS1 CNN3 COCH KIAA1644 PARP9 KRT5 MYL9 BBOX1 TRIB2 ASRGL1 GBP1 CLDN16 LGALS14 IGFBP4 ARF4L EMID1 RYK LOC400759 LOC401492 TRAD C2orf23 FGFR1 SOX17 CCDC3 MGC8685 MYLK PLEKHK1 PROS1 JAM2 AR SOX11 GPC4 MOXD1 IGFBP2 EFNB1 SLC26A7 EDN1 LOC400043 TITF1 TMOD2* -3.618 -3.679 -3.740 -3.746 -3.762 -3.780 -3.802 -3.812 -3.861 -3.931 -3.935 -3.955 -3.959 -3.970 -4.029 -4.034 -4.035 -4.135 -4.143 -4.154 -4.174 -4.196 -4.224 -4.226 -4.257 -4.323 -4.405 -4.440 -4.448 -4.484 -4.491 -4.589 -4.633 -4.649 -4.744 -4.849 -4.868 -4.873 -4.943 -5.055 -5.092 -5.092 Summary of Function Cell signalling Cellular metabolism Transcription regulation Signal transduction Transporter Cell adhesion Transcription factor Proteolysis Insulin receptor signalling Calmodulin binding Perception of sound Enzyme; cell migration Cytoskeleton; protein binding Calcium ion binding Electron transport Regulation of MAPK activity Cellular metabolism Immune response Cell adhesion; ion transport Sugar binding Cell growth; cell proliferation Signal transduction Protein binding Signal transduction Signal transduction MAPKKK signalling cascade Transcription regulation Protein polymerisation Signal transduction Blood coagulation Cell adhesion Cell growth; cell signalling Transcription factor Cell proliferation Cellular metabolism Cell growth Cell proliferation; cell signalling Transporter Cell signalling Transcription factor Cell signalling Average fold change represents the mean fold change value obtained from averaging the fold change for Batch A and Batch B * Gene with duplicated probe Appendix Phalanx Probe ID PH_hs_0023739 PH_hs_0013732 PH_hs_0031572 PH_hs_0003518 PH_hs_0001151 PH_hs_0013028 PH_hs_0025078 PH_hs_0033196 PH_hs_0006770 PH_hs_0032346 PH_hs_0005820 PH_hs_0003194 PH_hs_0004276 PH_hs_0024509 PH_hs_0028961 PH_hs_0022302 PH_hs_0028708 PH_hs_0000236 PH_hs_0018787 PH_hs_0027279 PH_hs_0004511 PH_hs_0037802 PH_hs_0019248 PH_hs_0031396 PH_hs_0005906 PH_hs_0015664 PH_hs_0005801 PH_hs_0031238 PH_hs_0005998 PH_hs_0035772 PH_hs_0014200 PH_hs_0010088 PH_hs_0016413 PH_hs_0002908 PH_hs_0016036 # GeneBank ID NM_152282 NM_002430 NM_002237 NM_012427 NM_178496 NM_005725 NM_001394 NM_005823 NM_025216 NM_152282 NM_018004 NM_021255 NM_016083 NM_006820 NM_000165 NM_001617 NM_000346 NM_002193 NM_004120 NM_020698 NM_003652 BX640888 NM_005302 NM_001683 NM_000076 NM_002982 NM_007196 NM_002986 NM_004626 NM_002982 NM_002776 NM_014289 NM_018476 NM_020386 NM_032539 Entrez Gene Name ACPL2* MN1 KCNG1 KLK5 LOC151963 TIMP3 DUSP4 MSLN WNT10A ACPL2* FLJ10134 PELI2 CNR1 IFI44L GJA1 ADD2 SOX9 INHBB GBP2 KIAA1145 CPZ GPC6 GPR37 ATP2B2 CDKN1C CCL2* KLK8 CCL11 WNT11 CCL2* KLK10 CAPN6 BEX1* HRASLS SLITRK2 Average Fold Change# -5.145 -5.293 -5.328 -5.375 -5.636 -5.649 -5.744 -5.768 -5.874 -6.045 -6.191 -6.258 -6.281 -6.359 -6.439 -6.742 -6.798 -7.272 -7.310 -7.961 -8.492 -8.538 -9.162 -10.631 -11.060 -11.482 -11.491 -12.915 -13.365 -14.805 -15.260 -15.400 -16.615 -26.365 -52.540 Summary of Function acid phosphatase-like Cell cycle progression Transporter Proteolysis Apoptosis Cell cycle; MAPKKK signalling Cell adhesion Cell signalling Protein binding Cell signalling Cell signalling; gap junction Metalion binding Transcription factor; protein binding Cell growth; cell differentiation Nucleotide binding Metal ion binding Signal transduction Calcium ion and calmodulin binding Cell cycle arrest Chemokine (C-C motif) ligand Proteolysis Immune response; cell signalling Signal transduction Antiapoptosis; signal transduction Cell cycle; proteolysis Proteolysis  Cell differentiation Protein binding Average fold change represents the mean fold change value obtained from averaging the fold change for Batch A and Batch B * Gene with duplicated probe [...]... Acid in Modulating the Cytotoxic Effects of Arsenic Trioxide in Ovarian Carcinoma Cell Lines (Manuscript in preparation) 4 Pei-shi Ong, Yuhong Du, Parsons PG, Sui-Yung Chan and Paul Chi-Lui Ho Arsenic Trioxide Induces Cell Death in Ovarian Cancer Cells via a CaspaseIndependent Pathway with a Partial Death-Protective Effect by Bclxl (Manuscript in preparation) Contribution to other publication during... Ho Arsenic Trioxide induced a Caspase-independent Cell Death involving the Downregulation of Bclxl in Cisplatin Resistant Ovarian Cancer Cell Line-OVCAR-3 97th American Association Publications and Conference Abstracts XI of Cancer Research Annual Meeting Washington DC April 2006 Avon Foundation Scholar -in- Training award recipient 4 Pei-shi Ong, Yuhong Du, Sui-Yung Chan, Paul Chi Lui Ho Understanding... Lui Ho Understanding the Mechanism of Arsenic trioxide in Ovarian Cancer Cell Lines - Preliminary Data 17th Singapore Pharmacy Congress, Jul 2005, Singapore Best presenter award recipient Pharmaceutics category 5 Pei-shi Ong, Sui-Yung Chan, Paul Chi Lui Ho Buthionine Sulfoximine But Not Ascorbic Acid Enhances Cytotoxicity of Arsenic Trioxide in Ovarian Cancer Cell Lines Through Modulation of Glutathione... are involved in cytokine processing and inflammation, at least seven caspases (caspases 2, 3, 6, 7, 8, 9, 10) participate in cell death The caspases that are involved in apoptotic signaling and execution can be further classified into initiator caspases (caspase 2, 8, 9, 10) and effector caspases (caspase 3, 6, 7) Initiator caspases are caspases containing a long N-terminal prodomain The long prodomain... Pressure Asher HPA-S …………………………………………………………… ICP-MS main instrument settings ……………………………… IC50 values (mean ± SD) of As2O3 in ovarian cancer cell lines after drug treatment with As2O3 alone or in combination with BSO ……………………………………………………………… IC50 values (mean ± SD) of As2O3 in ovarian cancer cell lines after drug treatment with As2O3 alone or in combination with AA Cell cycle analysis of OVCAR-3/AsR... Cddp, SAHA and MS-275 in ovarian cancer cell lines after 48 hrs of treatment ……………… Combination indices for the drug combinations in OVCAR-3 cells ……………………………………………………………… Combination indices for the drug combinations in SKOV-3 cells IC50 values of Cddp in OVCAR-3 cells after concurrent treatment with therapeutically achievable levels of SAHA ……………… IC50 values (mean ± SD) of Cddp in SKOV-3 cells after... Ho In Vitro Assessment of Synergistic and Antagonistic Combinations of Cytotoxic Agents in Ovarian Cancer Cell Lines (Manuscript in preparation) 2 Pei-shi Ong, Sui-Yung Chan and Paul Chi-Lui Ho Establishment of an ArsenicResistant Ovarian Cancer Cell Line and Characterization of its Molecular Signature (Manuscript in preparation) 3 Pei-shi Ong, Sui-Yung Chan and Paul Chi-Lui Ho Buthionine Sulfoximine... Sequencing Project HMGB1 High-mobility group box 1 protein HDAC Histone deacetylases HDACIs Histone deacetylase inhibitors HF Human dermal fibroblasts H2O2 Hydrogen peroxide HCD Hydrophobic C terminal domain HEPES 4-(2-hydroxyethyl)-1-piperazineethanesulfonic  OH Hydroxyl radical IAPs Inhibitor of apoptosis proteins IB Inhibitor of κB IC 50 Inhibitory concentration 50% ICE Interleukin 1--converting... Phosphate-buffered saline PS Phosphatidylserine PI Popidium idodine PCD Programmed cell death PML promyelocytic leukemia gene QTc QT heart rate corrected interval ROS Reactive oxygen species As 2 S 2 Realgar RIP Receptor-interacting protein NADPH Reduced nicotinamide adenine dinucleotide phosphate RARα Retinoic acid receptor alpha Rh Rhodamine RNase A Ribonuclease A RPMI Roswell Park Memorial Institute SAHA... Caspase-independent cell death triggered by cytotoxic agents … Key events in the medicinal use of arsenic ……………………… Acute toxicities associated with APL patients undergoing As2O3 chemotherapy …………………………………………………… IC50 values of As2O3, Paclitaxel and Cddp in in vitro growth inhibition assay in ovarian cancer cell lines and normal human fibroblast cells …………………………………………………… Parameter for cell digestion using . 4-17 Intracellular GPx level in ovarian cancer cell lines ……………… 4-18 Intracellular CAT level in ovarian cancer cell lines …………… 4-19 Intracellular arsenic concentration in ovarian cancer. Sui-Yung Chan, Paul Chi Lui Ho. Arsenic Trioxide induced a Caspase-independent Cell Death involving the Downregulation of Bclxl in Cisplatin Resistant Ovarian Cancer Cell Line-OVCAR-3. 97th American. increase in cellular arsenic levels, suggesting that transporter mediated efflux of arsenic- GSH conjugate may play a role in determining arsenic sensitivity of ovarian carcinoma cells. In this