SUPPLEMENTAL DIGITAL CONTENT (SDC) SDC-METHODS …

SUPPLEMENTAL DIGITAL CONTENT (SDC)

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SDC-METHODS Microarray processing: Total RNA was reverse-transcribed using the One-Cycle Target

Labeling kit or the 3’ IVT Express kit from Affymetrix (Santa Clara, CA) following the

manufacturer’s protocol. Samples were then hybridized to Affymetrix GeneChip Human Genome

U133A v2.0 arrays, scanned with a GeneChip Scanner 3000 and the CEL files processed using the

GeneChip Operating software, version 5.0.

Interaction networks and functional analysis: Gene ontology and gene interaction

analyses were carried out using ToppGene [1] and Ingenuity Pathways Analysis (IPA, Ingenuity®

Systems, Redwood City, CA). Gene lists containing Entrez GeneIDs (ToppGene) or Affymetrix

IDs (IPA) were used as inputs. A Bonferroni correction was used in the Toppgene analyses while

the default settings were used for IPA. Biological functions and pathways with a p-value <0.05

were considered significant in the analyses.

Cytoscape: Cytoscape [2] was used to create a single gene interaction network from the

differentially expressed genes. The MiMI [3] plug-in was used to individually query six protein-

protein interaction databases - BIND, IntAct, DIP, MINT, CCSB, MDC [4-9] - and create separate

interaction networks. The GeneMania [10] plug-in was also used as a second source of protein-

protein interaction information. The individually generated networks were then merged, duplicate

interactions were removed and only first neighbors shared by two or more query genes were

retained. Biological processes were then identified from genes within the network and mapped

using the BiNGO [11] plug-in. To reduce the complexity of the figure only biological processes

with p-values <0.001 after a Bonferroni correction were mapped.

Validation of microarray results: Real-time (RT) quantitative-PCR (qPCR) reactions were

used for quantifying the expression of CCL5 (chemokine (C-C motif) ligand 5, Hs99999048_m1),


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ITGB2 (integrin, beta 2 (complement component 3 receptor 3 and 4 subunit), Hs00164957_m1),

CXCR4 (chemokine (C-X-C motif) receptor 4, Hs00976734_m1), and EGF (epidermal growth

factor, Hs00153181_m1) using pre-developed TaqMan® gene expression assays (Life

Technologies, Grand Island, NY). Glyceraldehyde 3-phosphate dehydrogenase (GAPDH, ID:

4310884E) expression was used as the endogenous control for normalization. Threshold cycle (Ct)

values were used to calculate relative expression using the ∆∆Ct method.


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REFERENCES for SDC-METHODS

[1] Chen J, Bardes EE, Aronow BJ, Jegga AG (2009) ToppGene Suite for gene list enrichment analysis and candidate gene prioritization. Nucleic Acids Res 37:W305-11.

[2] Smoot ME, Ono K, Ruscheinski J, Wang PL, Ideker T (2011) Cytoscape 2.8: new features for data integration and network visualization. Bioinformatics 27:431-432.

[3] Gao J, Ade AS, Tarcea VG, Weymouth TE, Mirel BR, Jagadish HV, States DJ (2009) Integrating and annotating the interactome using the MiMI plugin for cytoscape. Bioinformatics 25:137-138.

[4] Isserlin R, El-Badrawi RA, Bader GD (2011) The Biomolecular Interaction Network Database in PSI-MI 2.5. Database (Oxford) 2011:baq037.

[5] Aranda B, Achuthan P, Alam-Faruque Y, Armean I, Bridge A, Derow C, Feuermann M, Ghanbarian AT, Kerrien S, Khadake J et al. (2010) The IntAct molecular interaction database in 2010. Nucleic Acids Res 38:D525-31.

[6] Salwinski L, Miller CS, Smith AJ, Pettit FK, Bowie JU, Eisenberg D (2004) The Database of Interacting Proteins: 2004 update. Nucleic Acids Res 32:D449-51.

[7] Ceol A, Chatr Aryamontri A, Licata L, Peluso D, Briganti L, Perfetto L, Castagnoli L, Cesareni G (2010) MINT, the molecular interaction database: 2009 update. Nucleic Acids Res 38:D532-9.

[8] Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N et al. (2005) Towards a proteome-scale map of the human protein-protein interaction network. Nature 437:1173-1178.

[9] Stelzl U, Worm U, Lalowski M, Haenig C, Brembeck FH, Goehler H, Stroedicke M, Zenkner M, Schoenherr A, Koeppen S et al. (2005) A human protein-protein interaction network: a resource for annotating the proteome. Cell 122:957-968.

[10] Montojo J, Zuberi K, Rodriguez H, Kazi F, Wright G, Donaldson SL, Morris Q, Bader GD (2010) GeneMANIA Cytoscape plugin: fast gene function predictions on the desktop. Bioinformatics 26:2927-2928.

[11] Maere S, Heymans K, Kuiper M (2005) BiNGO: a Cytoscape plugin to assess overrepresentation of gene ontology categories in biological networks. Bioinformatics 21:3448-3449.


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SDC-FIGURE 1.

Variable by Variable Spearman ρ Prob>|ρ|

eGFR 3mo eGFR 1mo 0.8035 <0.001

eGFR 6mo eGFR 1mo 0.7876 <0.001

eGFR 9mo eGFR 1mo 0.7436 <0.001

eGFR 12mo eGFR 1mo 0.7076 <0.001

eGFR 15mo eGFR 1mo 0.6827 <0.001

eGFR 18mo eGFR 1mo 0.7254 <0.001

eGFR 21mo eGFR 1mo 0.6976 <0.001

eGFR 24mo eGFR 1mo 0.7717 <0.001

A B

SDC-Figure 1. Correlation of eGFR at different time points. A. Scatterplot matrix

comparing the eGFR values at each time point after segregation of patients based on their 1-month

eGFR. B. Table insert with Spearman’s rank correlations between eGFR values at each time point.


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SDC-FIGURE 2.

GroupMean

(Recipient Age ‐Donor Age)Mean

((Recipient Age + Donor Age)/2)GFR‐high 11.8 43.3GFR‐lo 11.0 49.5p‐value (across groups) 0.8348 0.0028

‐40

‐20

0

20

40

60

80

‐20 ‐10 0 10 20 30 40 50 60 70 80

Differen

ce (R

ecipient Age

‐Don

or Age)

Mean ((Recipient Age + Donor Age)/2)

SDC-Figure 2. Age comparison between the two sample groups. Scatterplot of the Mean

(Recipient Age + Donor Age)/2) vs. the Difference (Recipient Age – Donor Age) between

recipient and donor age by group. GFR-low (red) subjects tended to be composed of older

donor-recipient pairs compared to the GFR-high (green) subjects. There was a statistical

significant difference between the two groups when comparing means (table insert).


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SDC-FIGURE 3.

SDC-Figure 3. Network of biological processes identified. Biological processes identified

from up-regulated differentially expressed genes within the gene interaction network in Figure 2.

The size of the category indicates the number of genes indentified within that category; the

coloring represents the p-value according to the scale (inset). To reduce the complexity of the

analysis only biological processes with p-values <0.001 after a Bonferroni correction were

mapped.

p-value


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SDC-FIGURE 4.

SDC-Figure 4. Network analysis by Ingenuity Pathway. Merging of the top 2 scoring

networks identified by IPA from the differentially expressed genes between GFR-high and GFR-

low. Solid lines represent direct interaction; dashed lines represent indirect interactions. The

coloring indicates whether the gene was up-regulated (red) or down-regulated (green).


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SDC-FIGURE 5.

SDC-Figure 5. Results from the Random Forest algorithm. Relative importance based on

permutation procedure of the probesets and clinical values identified by the random forest

algorithm as important predictors of graft function post-transplantation.


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-15

-10

-5

0

5

10

15

Fold

Cha

nge

Det

ecte

d by

Mic

roar

ray

PI K3 IFTA

SDC-FIGURE 6.

SDC-Figure 6. Fold changes of selected genes detected in PI and K3 biopsies. Graphical

representation of the fold changes detected by microarray of the 42 genes found to be

differentially expressed between GFR-high and GFR-low patient groups at pre-implantation (PI,

blue diamonds), 3-months post-transplant (K3, red diamonds) and between NFA and CAD with

IF/TA (IFTA, green diamonds) samples.


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SDC-Table 1. DGF diagnoses. Diagnosed DGF causes listed by subject group. Oliguria

was a common diagnosis within the GFR-low group while hyperkalemia was more often diagnosed within the GFR-high group.

Sample ID DGF Cause eGFR (1mo) Group 51 Fluid Overload 95.5 GFR-high 123-K Fluid Overload, Uremia 80.7 GFR-high 57 Hyperkalemia 78.7 GFR-high 178-K Hyperkalemia 76.6 GFR-high 125-K Hyperkalemia 75.3 GFR-high 89-K Hyperkalemia 75.0 GFR-high 71-K Oliguria 69.8 GFR-high 83-K Hyperkalemia 66.4 GFR-high 122-K Hyperkalemia, Oliguria 63.9 GFR-high 54 Hyperkalemia 61.6 GFR-high 102 Oliguria 55.1 GFR-high 96 Hyperkalemia 54.9 GFR-high 45 Hyperkalemia 50.7 GFR-high 34 Fluid Overload 50.0 GFR-high 95 Hyperkalemia/Oliguria 40.4 GFR-low 85 Oliguria 39.3 GFR-low 105-K Oliguria 38.4 GFR-low 64-K Hyperkalemia 38.3 GFR-low 50 Uremia 37.3 GFR-low 137-K Anuria 35.6 GFR-low 3-NK-9 Oliguria 35.4 GFR-low 79-K Hyperkalemia 32.2 GFR-low 104 Oliguria 30.5 GFR-low 103 Oliguria 29.3 GFR-low 144-K Oliguria 23.7 GFR-low 80-K Oliguria 23.2 GFR-low 20 Oliguria 22.8 GFR-low 66 Anuria 19.6 GFR-low 110 Hyperkalemia 16.9 GFR-low 106 Hyperkalemia/Oliguria 15.6 GFR-low 98 Oliguria 11.6 GFR-low 99 Hyperkalemia/Oliguria 10.7 GFR-low 97 Hyperkalemia/Oliguria 9.6 GFR-low 1 Hyperkalemia, orthopnea 8.3 GFR-low


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SDC-Table 2. Differentially expressed genes. Complete list of differentially expressed genes (n=197) identified by comparing GFR-low (patients with eGFR ≤45 mL/min/1.73m2) and GFR-high (patients with eGFR >45 mL/min/1.73m2).

Affymetrix ID Gene Symbol Entrez ID p-value FDR 1405_i_at CCL5 6352 1.15E-06 0.0207 206336_at CXCL6 6372 8.48E-06 0.0357 203535_at S100A9 6280 1.17E-05 0.0357 204655_at CCL5 6352 4.94E-06 0.0357 210915_x_at TRBC1 28639 6.08E-06 0.0357 202803_s_at ITGB2 3689 1.39E-05 0.0357 213095_x_at AIF1 199 1.27E-05 0.0357 34210_at CD52 1043 1.73E-05 0.0388 204118_at CD48 962 2.42E-05 0.0482 202237_at NNMT 4837 7.69E-05 0.0531 209173_at AGR2 10551 5.29E-05 0.0531 213182_x_at CDKN1C 1028 7.48E-05 0.0531 204971_at CSTA 1475 7.26E-05 0.0531 210889_s_at FCGR2B 2213 6.44E-05 0.0531 204661_at CD52 1043 5.10E-05 0.0531 205488_at GZMA 3001 8.02E-05 0.0531 211796_s_at TRBC1 28638 7.25E-05 0.0531 205267_at POU2AF1 5450 7.03E-05 0.0531 206666_at GZMK 3003 7.80E-05 0.0531 209901_x_at AIF1 199 4.86E-05 0.0531 204639_at ADA 100 4.62E-05 0.0531 204769_s_at TAP2 6891 8.57E-05 0.0531 211499_s_at MAPK11 5600 5.57E-05 0.0531 1729_at TRADD 8717 4.39E-05 0.0531 217147_s_at TRAT1 50852 5.80E-05 0.0531 208813_at GOT1 2805 7.74E-05 0.0531 206716_at UMOD 7369 6.08E-05 0.0531 213167_s_at SLC5A3 6526 8.53E-05 0.0531 206404_at FGF9 2254 8.11E-05 0.0531 217028_at CXCR4 7852 9.68E-05 0.0571 217235_x_at IGL@ 28813 9.85E-05 0.0571 215051_x_at AIF1 199 0.000119525 0.0651 206545_at CD28 940 0.000118515 0.0651 202238_s_at NNMT 4837 0.000134599 0.0704 209598_at PNMA2 10687 0.000155058 0.0704 213566_at RNASE6 6039 0.000145893 0.0704


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204774_at EVI2A 2123 0.000155165 0.0704 204175_at ZNF593 51042 0.000145618 0.0704 213603_s_at RAC2 5880 0.000140622 0.0704 204829_s_at FOLR2 2350 0.000162069 0.0704 214463_x_at HIST1H4J 8363 0.000164576 0.0704 207981_s_at ESRRG 2104 0.000160779 0.0704 213539_at CD3D 915 0.000177753 0.0743 209795_at CD69 969 0.000198119 0.0809 218681_s_at SDF2L1 23753 0.000224535 0.0896 221601_s_at FAIM3 9214 0.000234044 0.0914 216894_x_at CDKN1C 1028 0.000244241 0.0934 219358_s_at ADAP2 55803 0.000252545 0.0945 209083_at CORO1A 11151 0.000271657 0.0957 206134_at ADAMDEC1 27299 0.000269038 0.0957 213160_at DOCK2 1794 0.000266628 0.0957 212999_x_at HLA-DQB1 3119 0.000351209 0.1014 211742_s_at EVI2B 2124 0.0003026 0.1014 202902_s_at CTSS 1520 0.000375829 0.1014 219534_x_at CDKN1C 1028 0.000355963 0.1014 213241_at PLXNC1 10154 0.000306087 0.1014 203741_s_at ADCY7 113 0.000359204 0.1014 204858_s_at TYMP 1890 0.000327878 0.1014 209906_at C3AR1 719 0.000344921 0.1014 204034_at ETHE1 23474 0.000378032 0.1014 213193_x_at TRBC1 28639 0.000367057 0.1014 203575_at CSNK2A2 1459 0.000367252 0.1014 205641_s_at TRADD 8717 0.000346173 0.1014 202508_s_at SNAP25 6616 0.000324234 0.1014 221767_x_at HDLBP 3069 0.000365373 0.1014 220281_at SLC12A1 6557 0.0003315 0.1014 206254_at EGF 1950 0.000298202 0.1014 202856_s_at SLC16A3 9123 0.000394355 0.1028 201056_at GOLGB1 2804 0.000394836 0.1028 202137_s_at ZMYND11 10771 0.000417892 0.1072 212998_x_at HLA-DQB1 3119 0.000430278 0.1074 200971_s_at SERP1 27230 0.000427562 0.1074 212613_at BTN3A2 11118 0.00044965 0.1099 205279_s_at GLRB 2743 0.000452888 0.1099 202953_at C1QB 713 0.000479873 0.1149 211384_s_at CASR 846 0.000492261 0.1164 203641_s_at COBLL1 22837 0.000526223 0.1228 216576_x_at IGKC 28299 0.000542987 0.1231 205886_at REG1B 5968 0.000555558 0.1231 204057_at IRF8 3394 0.000549227 0.1231


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204698_at ISG20 3669 0.00055835 0.1231 210403_s_at KCNJ1 3758 0.000561675 0.1231 212768_s_at OLFM4 10562 0.000612667 0.1237 219607_s_at MS4A4A 51338 0.000597181 0.1237 203643_at ERF 2077 0.000609901 0.1237 211663_x_at PTGDS 5730 0.00058674 0.1237 204891_s_at LCK 3932 0.000602234 0.1237 215785_s_at CYFIP2 26999 0.000608793 0.1237 213894_at THSD7A 221981 0.000581038 0.1237 204122_at TYROBP 7305 0.000647727 0.1251 32128_at CCL18 6362 0.00062717 0.1251 207233_s_at MITF 4286 0.000647188 0.1251 213164_at SLC5A3 6526 0.000645898 0.1251 218388_at PGLS 25796 0.000658416 0.1258 222001_x_at LOC728855 728855 0.000680253 0.1286 215946_x_at IGLL3 91353 0.000709486 0.1301 213348_at CDKN1C 1028 0.00070994 0.1301 203760_s_at SLA 6503 0.000708682 0.1301 200708_at GOT2 2806 0.000718363 0.1304 208892_s_at DUSP6 1848 0.000728837 0.1309 206467_x_at RTEL1 51750 0.000752141 0.1338 211748_x_at PTGDS 5730 0.000775971 0.1367 204169_at IMPDH1 3614 0.000799921 0.1392 210916_s_at CD44 960 0.000806073 0.1392 213831_at HLA-DQA1 3117 0.000825702 0.1393 214770_at MSR1 4481 0.000815298 0.1393 205681_at BCL2A1 597 0.000829531 0.1393 209752_at REG1A 5967 0.000843477 0.1403 211654_x_at HLA-DQB1 3119 0.00087131 0.1423 216081_at LAMA4 3910 0.000868303 0.1423 219118_at FKBP11 51303 0.000882509 0.1428 214768_x_at FAM20B 9917 0.000922764 0.1429 202207_at ARL4C 10123 0.000917289 0.1429 218232_at C1QA 712 0.000921215 0.1429 205436_s_at H2AFX 3014 0.000899015 0.1429 204053_x_at PTEN 5728 0.000900997 0.1429 211645_x_at Affy_211645_x_at 0 0.000973679 0.1482 216380_x_at LOC728453 728453 0.00096721 0.1482 216569_at Affy_216569_at 0 0.000987983 0.1492 218659_at ASXL2 55252 0.001005701 0.1506 202779_s_at LOC731049 27338 0.001022989 0.1519 213537_at HLA-DPA1 3113 0.001036231 0.1526 208891_at DUSP6 1848 0.001049371 0.1528 204786_s_at IFNAR2 3455 0.001071884 0.1528


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212873_at HMHA1 23526 0.001070331 0.1528 213447_at IPW 3653 0.001059082 0.1528 217148_x_at IGL@ 3535 0.001096654 0.1538 211656_x_at HLA-DQB1 3119 0.001104718 0.1538 214470_at KLRB1 3820 0.001090774 0.1538 206460_at AJAP1 55966 0.001129949 0.154 221978_at HLA-F 3134 0.001126621 0.154 210039_s_at PRKCQ 5588 0.001131711 0.154 212592_at IGJ 3512 0.001145286 0.1547 221710_x_at FAM176B 100133999 0.001163373 0.156 219709_x_at FAM173A 65990 0.001204019 0.1591 212944_at SLC5A3 6526 0.001204281 0.1591 205098_at CCR1 1230 0.001231044 0.1603 215692_s_at MPPED2 744 0.00123115 0.1603 206245_s_at IVNS1ABP 10625 0.001241845 0.1605 204466_s_at SNCA 6622 0.001283018 0.1615 215429_s_at ZNF428 126299 0.001285924 0.1615 206978_at CCR2 1231 0.001272492 0.1615 206087_x_at HFE 3077 0.001262561 0.1615 212588_at PTPRC 5788 0.001317219 0.1643 204446_s_at ALOX5 240 0.001345265 0.1661 218024_at BRP44L 51660 0.001350011 0.1661 204563_at SELL 6402 0.001380762 0.1687 202937_x_at RRP7A 27341 0.001397338 0.1696 214777_at IGKV4-1 28908 0.001474591 0.1756 202096_s_at TSPO 706 0.001485498 0.1756 219014_at PLAC8 51316 0.001483059 0.1756 204503_at EVPL 2125 0.001461412 0.1756 217478_s_at HLA-DMA 3108 0.001540559 0.1797 220357_s_at SGK2 10110 0.001531499 0.1797 204268_at S100A2 6273 0.001562135 0.1798 204647_at HOMER3 9454 0.001606004 0.1798 212587_s_at PTPRC 5788 0.001590847 0.1798 203349_s_at ETV5 2119 0.001585525 0.1798 203113_s_at EEF1D 1936 0.001609241 0.1798 206682_at CLEC10A 10462 0.001611097 0.1798 221810_at RAB15 376267 0.001560048 0.1798 201721_s_at LAPTM5 7805 0.001629528 0.1806 205508_at SCN1B 6324 0.001638259 0.1806 207047_s_at CLCNKA 1187 0.001678429 0.1839 209567_at RRS1 23212 0.001705086 0.1845 201251_at PKM2 5315 0.001695986 0.1845 217118_s_at C22orf9 23313 0.001721962 0.1852 216401_x_at LOC652493 652493 0.001763841 0.1863


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205200_at CLEC3B 7123 0.001769986 0.1863 46665_at SEMA4C 54910 0.001773041 0.1863 210165_at DNASE1 1773 0.001765695 0.1863 218387_s_at PGLS 25796 0.001792642 0.187 203507_at CD68 1973 0.001807627 0.187 204980_at CLOCK 9575 0.00181082 0.187 205119_s_at FPR1 2357 0.001828376 0.1877 206247_at MICB 4277 0.001841677 0.188 204279_at PSMB9 5698 0.001962853 0.1899 211634_x_at IGHM 100133862 0.001915193 0.1899 201185_at HTRA1 5654 0.00187983 0.1899 203538_at CAMLG 819 0.001947952 0.1899 204007_at FCGR3B 2215 0.00197651 0.1899 204443_at ARSA 410 0.001970512 0.1899 217733_s_at TMSB10 9168 0.001935724 0.1899 208580_x_at HIST1H4A 121504 0.001961433 0.1899 200074_s_at RPL14 144581 0.001923767 0.1899 210038_at PRKCQ 5588 0.001950321 0.1899 213068_at DPT 1805 0.001892219 0.1899 214083_at LOC100132532 100132532 0.002009646 0.192 204912_at IL10RA 3587 0.002047531 0.1946 209606_at CYTIP 9595 0.002075498 0.1962 204220_at GMFG 9535 0.002105594 0.1971 217456_x_at HLA-E 3133 0.002117906 0.1971 214058_at MYCL1 4610 0.002110907 0.1971 204044_at QPRT 23475 0.002162966 0.1972 218132_s_at TSEN34 79042 0.00216069 0.1972 214775_at N4BP3 23138 0.002140185 0.1972 200855_at C20orf191 100133918 0.002160911 0.1972


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SDC-Table 3. Cox proportional hazards. Complete list of genes identified by Cox

proportional hazards when examining gene expression versus time-to-event effects. A positive log odds ratio indicates an increase in gene expression leads to worse outcomes; a negative log odds ratio indicates an increase in gene expression leads to improved outcomes.

Affymetrix ID Entrez ID Gene Symbol Log odds ratio p-value

217698_at 0 Affy_217698_at 10.74 0.00221 207590_s_at 2491 CENPI 6.62 0.00518 210088_x_at 4635 MYL4 6.25 0.00013 216516_at 0 Affy_216516_at 5.51 0.00099 208026_at 121504 HIST1H4A 5.36 0.00091 201249_at 6513 SLC2A1 5.35 0.00426 40640_at 29781 NCAPH2 5.14 0.00136 204887_s_at 10733 PLK4 4.82 0.00395 216812_at 0 Affy_216812_at 4.78 0.00374 216740_at 0 Affy_216740_at 4.69 0.00561 89948_at 63935 PCIF1 4.62 0.00371 204269_at 11040 PIM2 4.57 0.00275 58696_at 54512 EXOSC4 4.33 0.00011 221650_s_at 100133916 LOC100133916 4.23 0.00144 65521_at 51619 UBE2D4 4.21 0.00056 206199_at 1087 CEACAM7 4.15 0.00491 220518_at 25890 ABI3BP 4.07 0.0035 213523_at 898 CCNE1 3.98 0.00076 200715_x_at 23521 RPL13A 3.96 0.00626 216583_x_at 55651 NHP2 3.88 0.00022 211942_x_at 23521 RPL13A 3.84 0.00101 212541_at 80308 FLAD1 3.72 0.00651 222220_s_at 55815 TSNAXIP1 3.67 0.00198 205875_s_at 11277 ATRIP 3.51 0.00123 214825_at 728215 FAM155A 3.5 0.00651 210395_x_at 4635 MYL4 3.49 0.00671 203022_at 10535 RNASEH2A 3.45 0.00215 203040_s_at 3145 HMBS 3.39 0.00191 202120_x_at 1175 AP2S1 3.36 0.00116 207815_at 5197 PF4V1 3.36 0.00168 201840_at 4738 NEDD8 3.34 0.00137 212748_at 57591 MKL1 3.32 0.00191


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212317_at 23534 TNPO3 3.29 0.00051 211474_s_at 5269 SERPINB6 3.19 0.00946 207850_at 2921 CXCL3 3.17 0.00344 216421_at 0 Affy_216421_at 3.17 0.00358 202475_at 10430 TMEM147 3.16 0.00184 213368_x_at 8541 PPFIA3 3.1 0.00726 205186_at 7802 DNALI1 3.08 0.0035 213543_at 6444 SGCD 3.08 0.00432 210589_s_at 2629 GBA 3.03 0.00155 219706_at 55317 C20orf29 3.01 0.0055 218267_at 51550 CINP 2.99 0.00661 202257_s_at 10421 CD2BP2 2.97 0.00712 217934_x_at 10273 STUB1 2.97 0.0068 216505_x_at 93144 RPS10L 2.93 0.00156 206441_s_at 54939 COMMD4 2.92 0.00028 218354_at 51693 TRAPPC2L 2.92 0.00029 205785_at 3684 ITGAM 2.9 0.00249 213892_s_at 353 APRT 2.88 0.00182 216380_x_at 728453 LOC728453 2.88 0.00311 206487_at 23353 UNC84A 2.85 0.0031 215631_s_at 25855 BRMS1 2.78 0.0028 212961_x_at 541578 CXorf40A 2.76 0.00187 204697_s_at 1113 CHGA 2.75 0.00071 213315_x_at 91966 CXorf40A 2.74 0.0028 216606_x_at 653639 LYPLA2P1 2.74 0.00753 205481_at 134 ADORA1 2.73 0.00414 218985_at 29988 SLC2A8 2.73 0.00575 201400_at 5691 PSMB3 2.72 0.00755 204383_at 8220 DGCR14 2.71 0.0076 210908_s_at 5204 PFDN5 2.7 0.00946 206508_at 970 CD70 2.66 0.00274 208074_s_at 1175 AP2S1 2.66 0.00121 210386_s_at 4580 MTX1 2.66 0.0083 216569_at 0 Affy_216569_at 2.65 0.0087 219187_at 63943 FKBPL 2.63 0.00881 202726_at 3978 LIG1 2.62 0.00497 202041_s_at 9158 FIBP 2.61 0.00364 210448_s_at 5026 P2RX5 2.61 0.00516 209665_at 11068 CYB561D2 2.6 0.00749 203031_s_at 7390 UROS 2.58 0.00093


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203679_at 11018 TMED1 2.58 0.00159 211339_s_at 3702 ITK 2.58 0.00671 201004_at 6748 SSR4 2.57 0.00875 217368_at 517 ATP5G2 2.57 0.00912 218385_at 55168 MRPS18A 2.56 0.00568 214463_x_at 8363 HIST1H4J 2.55 0.00013 202941_at 4729 NDUFV2 2.54 0.00732 213539_at 915 CD3D 2.53 0.00007 218291_at 28956 ROBLD3 2.53 0.00332 219141_s_at 55626 AMBRA1 2.51 0.00803 202276_at 7979 SHFM1 2.5 0.00722 219742_at 80758 PRR7 2.5 0.00673 200075_s_at 2987 GUK1 2.49 0.0022 200736_s_at 2876 GPX1 2.46 0.00511 219203_at 51016 FAM158A 2.46 0.005 212691_at 23511 NUP188 2.44 0.00651 208827_at 5694 PSMB6 2.39 0.00226 218388_at 25796 PGLS 2.36 0.00421 218695_at 54512 EXOSC4 2.36 0.00067 218776_s_at 80021 TMEM62 2.35 0.00414 221597_s_at 29100 TMEM208 2.34 0.00608 213141_at 5681 PSKH1 2.29 0.00619 218034_at 51024 FIS1 2.29 0.00343 217817_at 10093 ARPC4 2.28 0.00761 59437_at 138162 C9orf116 2.25 0.00473 221710_x_at 100133999 FAM176B 2.24 0.00507 208580_x_at 121504 HIST1H4A 2.23 0.00145 212955_s_at 5438 POLR2I 2.22 0.00704 221693_s_at 55168 MRPS18A 2.21 0.00051 203342_at 10245 TIMM17B 2.2 0.00221 209394_at 8623 ASMTL 2.2 0.00881 211043_s_at 1212 CLTB 2.16 0.00202 218117_at 9978 RBX1 2.16 0.00878 202296_s_at 11079 RER1 2.12 0.00104 205829_at 3292 HSD17B1 2.12 0.00263 217559_at 140801 RPL10L 2.11 0.00824 203686_at 4350 MPG 2.09 0.00426 204175_at 51042 ZNF593 2.09 0.00404 205129_at 10360 NPM3 2.08 0.00355 218855_at 131601 GPR175 2.08 0.00617


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219162_s_at 65003 MRPL11 2.08 0.00607 204212_at 10005 ACOT8 2.07 0.00234 218391_at 11267 SNF8 2.07 0.00995 205662_at 27077 B9D1 2.05 0.00078 217683_at 3046 HBE1 2.01 0.00883 219861_at 55192 DNAJC17 2 0.00171 213095_x_at 199 AIF1 1.99 0.00467 221946_at 138162 C9orf116 1.99 0.00776 202839_s_at 4713 NDUFB7 1.98 0.00148 205634_x_at 254359 ZDHHC24 1.98 0.0044 209132_s_at 54939 COMMD4 1.97 0.00556 216178_x_at 3688 ITGB1 1.97 0.00562 217950_at 51070 NOSIP 1.97 0.00807 213540_at 7923 HSD17B8 1.96 0.00721 213753_x_at 1984 EIF5A 1.96 0.004 208837_at 23423 TMED3 1.94 0.00101 213897_s_at 6150 MRPL23 1.93 0.00238 214574_x_at 7940 LST1 1.93 0.0034 209531_at 2954 GSTZ1 1.9 0.0066 41047_at 79095 C9orf16 1.89 0.00361 204034_at 23474 ETHE1 1.87 0.0074 205237_at 2219 FCN1 1.87 0.00756 205504_at 695 BTK 1.87 0.00554 201526_at 381 ARF5 1.86 0.00422 218996_at 29844 TFPT 1.86 0.00372 204118_at 962 CD48 1.85 0.00035 213010_at 112464 PRKCDBP 1.84 0.00378 203168_at 1388 ATF6B 1.83 0.0081 202779_s_at 27338 LOC731049 1.8 0.00453 212983_at 3265 HRAS 1.8 0.00494 204880_at 4255 MGMT 1.78 0.00876 219021_at 55298 RNF121 1.77 0.00609 215051_x_at 199 AIF1 1.75 0.0058 204766_s_at 4521 NUDT1 1.73 0.0018 221518_s_at 55031 USP47 1.73 0.00769 222165_x_at 79095 C9orf16 1.72 0.00859 201577_at 4830 NME1 1.71 0.00714 210792_x_at 10572 SIVA1 1.69 0.00993 209901_x_at 199 AIF1 1.68 0.00492 91684_g_at 54512 EXOSC4 1.67 0.00697


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218531_at 80194 TMEM134 1.66 0.00522 204220_at 9535 GMFG 1.65 0.0033 204858_s_at 1890 TYMP 1.65 0.00297 205847_at 64063 PRSS22 1.64 0.00712 210534_s_at 27077 B9D1 1.64 0.00127 219576_at 79649 MAP7D3 1.62 0.00965 214744_s_at 9349 RPL23 1.61 0.00747 1861_at 572 BAD 1.6 0.00836 206284_x_at 1212 CLTB 1.6 0.00722 201543_s_at 56681 SAR1A 1.53 0.00831 203409_at 1643 DDB2 1.51 0.00873 203760_s_at 6503 SLA 1.5 0.00494 213060_s_at 1117 CHI3L2 1.5 0.00303 202096_s_at 706 TSPO 1.48 0.00311 218302_at 55851 PSENEN 1.48 0.00139 213603_s_at 5880 RAC2 1.47 0.00371 211456_x_at 645745 MT1P2 1.43 0.00586 209449_at 57819 LSM2 1.41 0.00358 209417_s_at 3430 IFI35 1.39 0.00926 202574_s_at 1455 CSNK1G2 1.37 0.00419 209579_s_at 8930 MBD4 1.37 0.00832 210915_x_at 28639 TRBC1 1.36 0.00314 212891_s_at 90480 GADD45GIP1 1.36 0.0074 216336_x_at 4493 MT1E 1.36 0.00132 219118_at 51303 FKBP11 1.35 0.00473 209622_at 8576 STK16 1.33 0.00415 209371_s_at 6452 SH3BP2 1.29 0.00819 214181_x_at 7940 LST1 1.29 0.00612 210524_x_at 0 Affy_210524_x_at 1.27 0.00387 206461_x_at 4496 MT1H 1.24 0.00653 202598_at 6284 S100A13 1.23 0.00963 213533_at 27065 D4S234E 1.21 0.00737 204661_at 1043 CD52 1.2 0.00347 219219_at 54958 TMEM160 1.18 0.00593 214149_s_at 8992 ATP6V0E1 1.15 0.00599 211833_s_at 581 BAX 1.12 0.00379 208581_x_at 4501 MT1X 1.11 0.00719 203923_s_at 1536 CYBB 1.1 0.00597 217165_x_at 4494 MT1F 1.1 0.00365 213629_x_at 4494 MT1F 1.06 0.00415


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200616_s_at 9761 MLEC 1.03 0.00836 211796_s_at 28638 TRBC1 1.01 0.00631 222029_x_at 10471 PFDN6 1.01 0.00437 202667_s_at 7922 SLC39A7 0.98 0.00974 206777_s_at 1415 CRYBB2 0.97 0.00532 204326_x_at 4501 MT1X 0.96 0.00657 210042_s_at 1522 CTSZ 0.73 0.00321 211074_at 2348 FOLR1 0.61 0.0052 209267_s_at 64116 SLC39A8 -0.56 0.00791 206254_at 1950 EGF -0.61 0.00703 220281_at 6557 SLC12A1 -0.73 0.00646 207549_x_at 4179 CD46 -0.81 0.00702 210735_s_at 771 CA12 -0.83 0.00512 215073_s_at 7026 NR2F2 -0.89 0.00441 211538_s_at 3306 HSPA2 -0.91 0.00726 218966_at 55930 MYO5C -0.92 0.00864 211574_s_at 4179 CD46 -0.94 0.00454 212560_at 6653 SORL1 -0.99 0.00819 215707_s_at 5621 PRNP -1 0.0054 203961_at 10529 NEBL -1.03 0.00268 212599_at 26053 AUTS2 -1.04 0.00616 206414_s_at 8853 ASAP2 -1.06 0.00101 211968_s_at 3320 HSP90AA1 -1.06 0.00257 212183_at 11163 NUDT4 -1.07 0.00865 213039_at 23370 ARHGEF18 -1.09 0.00482 213285_at 161291 TMEM30B -1.1 0.00859 219869_s_at 64116 SLC39A8 -1.1 0.00142 206716_at 7369 UMOD -1.12 0.00934 210403_s_at 3758 KCNJ1 -1.12 0.00637 208116_s_at 4121 MAN1A1 -1.13 0.00313 201726_at 1994 ELAVL1 -1.17 0.00501 208744_x_at 10808 HSPH1 -1.17 0.00733 203962_s_at 10529 NEBL -1.2 0.00023 202780_at 5019 OXCT1 -1.22 0.00198 212388_at 23358 USP24 -1.25 0.00934 201976_s_at 4651 MYO10 -1.27 0.00106 212944_at 6526 SLC5A3 -1.28 0.00341 205530_at 2110 ETFDH -1.31 0.00733 217122_s_at 728661 RP11-345P4.4 -1.32 0.0049 209772_s_at 100133941 CD24 -1.37 0.00848


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202171_at 7716 VEZF1 -1.38 0.00817 212390_at 727893 LOC727893 -1.38 0.00725 209443_at 5104 SERPINA5 -1.4 0.00988 209604_s_at 2625 GATA3 -1.42 0.0044 211150_s_at 1737 DLAT -1.47 0.00311 212568_s_at 1737 DLAT -1.49 0.00373 203420_at 51439 FAM8A1 -1.5 0.00731 203611_at 7014 TERF2 -1.53 0.00893 201363_s_at 10625 IVNS1ABP -1.54 0.00612 203642_s_at 22837 COBLL1 -1.55 0.00546 200867_at 55905 RNF114 -1.56 0.00207 212150_at 23167 EFR3A -1.56 0.00178 213167_s_at 6526 SLC5A3 -1.56 0.00169 203058_s_at 9060 PAPSS2 -1.58 0.00556 218218_at 55198 APPL2 -1.6 0.00108 202085_at 9414 TJP2 -1.61 0.00722 212215_at 9581 PREPL -1.61 0.00532 215549_x_at 100128553 CTAGE4 -1.61 0.00745 215945_s_at 23321 TRIM2 -1.63 0.0087 200683_s_at 7332 UBE2L3 -1.67 0.00902 204451_at 8321 FZD1 -1.67 0.0025 213149_at 1737 DLAT -1.68 0.00489 212381_at 23358 USP24 -1.76 0.00153 205522_at 3233 HOXD4 -1.82 0.00907 201837_s_at 9913 SUPT7L -1.85 0.00654 217725_x_at 26135 SERBP1 -1.88 0.00096 206385_s_at 288 ANK3 -1.91 0.00802 217448_s_at 285412 LOC285412 -1.93 0.00784 208783_s_at 4179 CD46 -1.96 0.00347 208773_s_at 404734 ANKHD1 -1.97 0.00511 203141_s_at 8546 AP3B1 -1.98 0.00374 202845_s_at 10928 RALBP1 -2 0.00803 208990_s_at 3189 HNRNPH3 -2.03 0.00439 222240_s_at 51477 ISYNA1 -2.06 0.00423 201799_s_at 5007 OSBP -2.07 0.00326 214113_s_at 9939 RBM8A -2.09 0.00969 201112_s_at 1434 CSE1L -2.12 0.00882 205788_s_at 9877 ZC3H11A -2.14 0.0075 209343_at 80303 EFHD1 -2.14 0.00011 201386_s_at 1665 DHX15 -2.16 0.00309


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201769_at 9685 CLINT1 -2.18 0.00312 211858_x_at 2778 GNAS -2.23 0.00546 211208_s_at 8573 CASK -2.24 0.0024 214548_x_at 2778 GNAS -2.25 0.00466 217920_at 10905 MAN1A2 -2.26 0.00535 212372_at 4628 MYH10 -2.28 0.00777 211971_s_at 10128 LRPPRC -2.37 0.0036 201928_at 8502 PKP4 -2.41 0.0008 217935_s_at 55245 UQCC -2.44 0.0075 208651_x_at 100133941 CD24 -2.47 0.00378 208683_at 824 CAPN2 -2.48 0.00101 204020_at 5813 PURA -2.53 0.00259 206235_at 3981 LIG4 -2.53 0.00111 200981_x_at 2778 GNAS -2.61 0.00258 200780_x_at 2778 GNAS -2.64 0.002 205963_s_at 9093 DNAJA3 -2.64 0.00878 201071_x_at 23451 SF3B1 -2.67 0.00157 212273_x_at 2778 GNAS -2.68 0.00177 209137_s_at 9100 USP10 -2.7 0.00233 215725_at 25786 DGCR11 -2.72 0.00933 216379_x_at 100133941 CD24 -2.79 0.00412 200850_s_at 10768 AHCYL1 -2.87 0.00128 213738_s_at 498 ATP5A1 -2.93 0.00361 220266_s_at 9314 KLF4 -3 0.00865 200912_s_at 1974 EIF4A2 -3.22 0.00931 208855_s_at 8428 STK24 -3.26 0.00554 209771_x_at 100133941 CD24 -3.3 0.00139 201778_s_at 9813 KIAA0494 -3.34 0.0022 211185_s_at 23451 SF3B1 -3.47 0.00131 212696_s_at 6047 RNF4 -3.55 0.00383 200693_at 10971 YWHAQ -3.65 0.0008 217758_s_at 56889 TM9SF3 -3.67 0.00093 200004_at 1982 EIF4G2 -3.88 0.00794 217839_at 10342 TFG -4.03 0.0012 200614_at 1213 CLTC -4.58 0.0046 220415_at 51086 TNNI3K -5.03 0.00479 207781_s_at 7552 ZNF711 -6.63 0.00643 220771_at 51152 LOC51152 -8.28 0.00983

SUPPLEMENTAL DIGITAL CONTENT (SDC) SDC-METHODS …

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