Characterization of Gene Expression Phenotype in Amyotrophic Lateral Sclerosis Monocytes

Supplementary Online Content

Zhao W, Beers DR, Hooten KG, et al. Characterization of Gene Expression Phenotype in Amyotrophic Lateral Sclerosis Monocytes. JAMA Neurol. Published online April 24, 2017. doi:10.1001/jamaneurol.2017.0357.

eFigure 1. Principle Component Analysis (PAC) Indicates That Positive Selection Failed to Distinguish ALS and Control Monocyte Samples While Negative Selected ALS Monocytes Were Distinguishable From Control Monocytes. eFigure 2. Venn Diagram of Differentially Expressed Genes (DEGs) in Monocytes From ALS Slow and Fast Patients eFigure 3. IL-8 Protein Levels in Sera of ALS Patients and Healthy Controls. eTable 1. DEGs of Monocytes Isolated From Total ALS Patients (vs Control) eTable 2. Disease Progression of ALS Patients for RNA-seq Study Based on a Cutoff of 1.5 AALS Points/Month or a Cutoff of 1.0 ALS FRS Points/Month eTable 3. 65 DEGs Solely Found in Monocytes From Slowly Progressing ALS Patients (vs Control) eTable 4. 237 DEGs Solely Found in Monocytes From Rapidly Progressing ALS Patients (vs Control) eTable 5. 43 DEGs Expressed in Monocytes of Both Slow and Fast Groups (vs Control)

This supplementary material has been provided by the authors to give readers additional information about their work.

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eFigure 1. Principle component analysis (PAC) indicates that positive selection failed to distinguish ALS and control monocyte samples while negative selected ALS monocytes were distinguishable from control monocytes.

Monocytes by CD14+ monocytes by negative selection positive selection ALS monocytes by negative selection Control monocytes by negative selection ALS CD14+ monocytes by positive selection Control CD14+ monocytes by positive selection

PAC represents the distribution of RNA expression data (FPKM) from positively selected CD14+ monocytes and Pan monocytes by negative selection. RNA expression data from positively selected CD14+ monocytes clustered together with no variation observed between ALS and control samples (purple circle). Significant differences were observed between ALS pan monocyte samples and controls (red circle).

Downloaded From: https://jamanetwork.com/ on 09/28/2021 eFigure 2. Venn diagram of differentially expressed genes (DEGs) in monocytes from ALS slow (n=13) and fast patients (n=9).

Downloaded From: https://jamanetwork.com/ on 09/28/2021 eFigure 3. IL-8 protein levels in sera of ALS patients and healthy controls.

A B IL-8 protein in serum 50

30 pg/ml 20

0 NC ALS

IL-8 protein in serum

80 *# 60

pg/ml 40

0 NC ALS SLOW ALS FAST

A: There was a trend for increased IL-8 protein in sera of all ALS patients (n=66) comparing with healthy controls (NC, n=32). B: The serum IL-8 levels were higher in rapidly progressing patients (ALS fast, n=36) than in slowly progressing ALS patients (n=30) or healthy controls (NC, n=32). * p<0.05 vs. NC; # p<0.05 vs. ALS slow.

Downloaded From: https://jamanetwork.com/ on 09/28/2021 eTable 1. DEGs of monocytes isolated from total ALS patients (vs. control) TransID Gen log2 p FDR TransID Gene log2 p F e Fold val Name Fold valu D Nam Chan ue Chan e R e ge ge NR_0460 ADI 1.367 0.0 0.16 NM_005304_chr FFAR3 1.533 0.00 0. 83_chr1 POR 02 19 1 1 1 4 NM_001 ADI 1.363 0.0 0.15 NM_001145776 FKBP5 3.97 0 0. 290629_ POR 02 _chr6 0 chr1 1 4 NM_001 ALC 1.847 0.0 0.16 NM_001160030 FLT1 1.858 0.00 0. 243283_ AM 02 _chr13 2 1 chr3 9 NM_001 AMZ 1.299 0.0 0.25 NM_006732_chr FOSB 2.351 0 0. 289054_ 2 05 19 0 chr17 1 NM_001 ARE 3.36 0 0.06 NM_001114171 FOSB 1.724 0.00 0. 657_chr4 G _chr19 1 1 4 NM_001 ARF 7.65 0 0.03 NM_005438_chr FOSL1 2.248 0 0. 242856_ IP2 11 0 chr11 2 NM_001 ARH 5.844 0.0 0.2 NM_015714_chr G0S2 1.789 0.00 0. 256025_ GAP 03 1 1 1 chr10 22 5 NM_212 ARL 1.058 0.0 0.13 NR_073568_chr GHRLOS 6.733 0.00 0. 460_chr7 4A 01 3 1 1 1 NM_001 ATF 1.117 0.0 0.13 NM_004951_chr GPR183 1.588 0 0. 030287_ 3 01 13 0 chr1 3 NM_017 BAI 7.053 0.0 0.16 NM_001001550 GRB10 2.316 0.00 0. 451_chr1 AP2 02 _chr7 4 2 7 1 NM_001 BAS 1.088 0.0 0.22 NM_001191013 GSTO2 5.387 0.00 0. 271606_ P1 04 _chr10 1 1 chr5 4 NR_0283 BRE 1.493 0.0 0.12 NM_001195422 GTPBP3 1.348 0.00 0. 08_chr2 -AS1 01 _chr19 3 2 1 NM_001 C6or 4.164 0.0 0.11 NM_001161587 GYS1 3.043 0.00 0. 287397_ f1 01 _chr19 4 2 chr6 2 NM_001 CAL 1.231 0.0 0.21 NM_004893_chr H2AFY 1.266 0 0. 199672_ U 04 5 0 chr7 7 NM_033 CCD 3.952 0.0 0.12 NM_001945_chr HBEGF 1.824 0 0. 626_chr C12 01 5 0 X 0 3 NM_005 CCI 1.377 0.0 0.15 NM_177551_chr HCAR2 1.056 0.00 0. 893_chr9 N 01 12 1 1 2 NM_020 CD2 1.941 0.0 0.15 NR_045406_chr HIF1A- 1.547 0.00 0. 404_chr1 48 01 14 AS2 5 2

Downloaded From: https://jamanetwork.com/ on 09/28/2021 1 3 NM_001 CD8 1.411 0 0.07 NM_001199829 HORMA 5.805 0.00 0. 251901_ 3 _chr1 D1 4 2 chr6 1 NM_001 CD8 1.281 0.0 0.12 NR_038366_chr HOTAIR 1.749 0 0. 040280_ 3 01 7 M1 0 chr6 4 NM_003 CH2 3.506 0.0 0.21 NM_001193322 IKBKE 1.088 0 0. 956_chr1 5H 04 _chr1 0 0 9 NM_000 CHR 3.191 0.0 0.12 NM_000572_chr IL10 1.859 0 0. 742_chr8 NA2 01 1 0 2 NM_001 CLI 1.024 0.0 0.24 NM_000576_chr IL1B 1.59 0 0. 287593_ C1 05 2 0 chr6 8 NM_001 COR 4.064 0.0 0.19 NM_000600_chr IL6 2.381 0.00 0. 276471_ O1C 03 7 1 1 chr12 4 NM_001 CXC 1.782 0 0.03 NM_000584_chr IL8 1.866 0 0. 511_chr4 L1 4 0 3 NM_002 CXC 1.792 0 0.04 NM_176786_chr IL9R 2.224 0.00 0. 089_chr4 L2 X 2 1 5 NM_002 CXC 1.375 0.0 0.19 NM_001199799 ILDR1 6.072 0.00 0. 090_chr4 L3 03 _chr3 5 2 4 NM_001 DIS 6.912 0.0 0.23 NM_001145000 ITGAV 1.451 0.00 0. 164541_ C1 05 _chr2 5 2 chr1 3 NM_004 DUS 1.224 0.0 0.24 NM_001287440 JADE1 1.043 0.00 0. 418_chr2 P2 05 _chr4 2 1 8 NM_001 EGR 1.848 0.0 0.21 NR_047655_chr KANSL3 2.271 0.00 0. 199881_ 3 04 2 1 1 chr8 1 NM_004 EGR 1.844 0.0 0.11 NM_001199866 KIF16B 1.01 0.00 0. 430_chr8 3 01 _chr20 2 1 7 NM_001 EGR 1.748 0.0 0.25 NM_181986_chr LILRA5 2.251 0 0. 199880_ 3 05 19 0 chr8 8 NM_183 EIF5 1.026 0 0.03 NR_047524_chr LINC011 8.096 0 0. 004_chr1 1 28 0 4 7 NM_001 EMP 1.227 0.0 0.18 NR_024409_chr LOC1001 4.838 0.00 0. 423_chr1 1 02 3 28164 2 1 2 8 NM_001 ERE 1.857 0 0.03 NM_012323_chr MAFF 1.977 0.00 0. 432_chr4 G 22 3 2 NM_001 ETF 2.078 0.0 0.19 NM_001161573 MAFF 1.917 0.00 0. 282185_ 1 03 _chr22 1 1 chr5 1

Downloaded From: https://jamanetwork.com/ on 09/28/2021 NM_005 ETV 1.118 0 0.08 NM_182763_chr MCL1 1.053 0 0. 240_chr1 3 1 0 3 NM_001 EXO 1.08 0.0 0.14 NM_001278215 MIER1 1.16 0.00 0. 013839_ C7 01 _chr1 4 2 chr17 1 NM_001 FAM 2.268 0.0 0.12 NR_040073_chr MIR181A 1.833 0.00 0. 184942_ 219 01 1 1HG 1 1 chr9 A 1 NM_001 FAM 6.209 0.0 0.2 NM_170739_chr MRPL11 1.089 0.00 0. 252270_ 69A 03 11 2 1 chr1 6 NM_133 FCA 3.499 0 0.04 NM_005746_chr NAMPT 1.118 0 0. 273_chr1 R 7 0 9 3 NM_133 FCA 2.175 0 0.05 NM_001283018 NAPB 2.833 0 0. 278_chr1 R _chr20 0 9 6 NM_133 FCA 2.012 0 0.01 NM_001146276 NCEH1 1.19 0.00 0. 272_chr1 R _chr3 3 1 9 9 NM_133 FCA 1.45 0 0.02 NM_001282211 NDRG2 2.792 0.00 0. 279_chr1 R _chr14 5 2 9 4 eTable 1. DEGs of monocytes isolated from total ALS patients (vs. control) (continued 1) TransID Gene log2 p FDR TransID Gene log2 p F Name Fold val Name Fold v D Change ue Cha al R nge u e NM_006 NEBL 21.422 0 0 NM_152386 SGPP2 1.09 0 0. 393_chr1 _chr2 2 0 0 9 NM_006 NEDD9 1.862 0 0.08 NM_001206 SLC16 2.44 0 0. 403_chr6 951_chr17 A3 2 0 7 NM_001 NEK6 1.063 0.0 0.23 NM_001206 SLC16 1.49 0. 0. 166167_ 05 952_chr17 A3 0 1 chr9 0 2 1 NM_001 NEK6 1.061 0.0 0.24 NM_001286 SLC2A 3.83 0 0. 166169_ 05 236_chr12 14 3 0 chr9 3 NM_005 NFIL3 1.296 0 0.03 NM_006931 SLC2A 1.08 0 0. 384_chr9 _chr12 3 9 0 4 NM_001 NKX3-1 3.637 0.0 0.12 NR_048538 SLC9A 2.40 0 0. 256339_ 01 _chr20 8 5 0 chr8 3 NM_006 NR4A2 1.909 0 0 NR_003542 SLED1 1.89 0. 0. 186_chr2 _chr4 4 0 1 0 1 1

Downloaded From: https://jamanetwork.com/ on 09/28/2021 NM_198 NUDT6 7.895 0 0.02 NM_001282 SMG6 1.22 0. 0. 041_chr4 326_chr17 4 0 1 0 5 2 NM_001 OR2B11 1.447 0 0.07 NM_003955 SOCS3 1.37 0. 0. 004492_ _chr17 8 0 1 chr1 0 6 2 NM_145 OSBPL5 3.261 0.0 0.11 NM_001177 SRPR 1.09 0. 0. 638_chr1 01 842_chr11 9 0 1 1 0 1 1 NM_020 OSM 1.832 0 0.04 NM_175052 ST8SIA 1.24 0 0. 530_chr2 _chr5 4 7 0 2 7 NM_001 PAAF1 2.414 0.0 0.13 NM_001289 SYTL2 5.38 0. 0. 267804_ 01 610_chr11 3 0 2 chr11 0 4 5 NM_057 PARD3B 7.313 0 0.03 NM_138810 TAGAP 1.07 0 0. 177_chr2 _chr6 0 5 NM_152 PARD3B 6.481 0.0 0.13 NM_001244 TFEC 7.26 0. 0. 526_chr2 01 583_chr7 4 0 2 0 1 3 NM_001 PARP8 1.078 0.0 0.17 NM_001286 THEMI 3.94 0 0. 178056_ 02 115_chr1 S2 1 0 chr5 1 NM_002 PER1 1.343 0.0 0.15 NM_001290 TIMM2 3.04 0. 0. 616_chr1 01 117_chr10 3B 9 0 1 7 0 1 NM_001 PEX11A 7.399 0.0 0.11 NM_032136 TKTL2 1.09 0. 0. 271572_ 01 _chr4 3 0 2 chr15 0 3 NM_001 PFKFB3 1.75 0.0 0.1 NR_073506 TMEM3 1.04 0. 0. 282630_ 01 _chr3 9A 8 0 1 chr10 0 3 1 NM_004 PFKFB3 1.426 0.0 0.13 NM_001270 TNFAI 1.47 0. 0. 566_chr1 01 507_chr6 P3 0 2 0 0 1 3 NM_001 PGAP2 6.123 0.0 0.25 NM_006290 TNFAI 1.32 0. 0. 256235_ 05 _chr6 P3 0 1 chr11 0 2 1 NM_007 PHLDA1 1.39 0.0 0.2 NM_001270 TNFAI 1.23 0. 0. 350_chr1 03 508_chr6 P3 7 0 1 2 0 5 1 NM_001 PIK3R5 1.318 0 0 NM_001167 TNFAI 2.33 0. 0. 251855_ 942_chr19 P8L1 0 1

Downloaded From: https://jamanetwork.com/ on 09/28/2021 chr17 0 2 1 NM_006 PLK2 1.467 0.0 0.12 NM_021202 TP53IN 1.46 0 0. 622_chr5 01 _chr20 P2 2 0 1 NM_004 PLK3 1.022 0 0.08 NM_001043 TPM3 2.49 0. 0. 073_chr1 353_chr1 8 0 1 0 2 1 NM_001 PMPCA 2.046 0.0 0.2 NM_001242 TREM1 1.44 0 0 282944_ 03 589_chr6 1 chr9 NM_001 PRDM1 1.241 0.0 0.17 NM_001282 TRMU 2.13 0. 0. 198_chr6 02 784_chr22 4 0 1 0 1 1 NM_147 PSMG2 2.452 0 0.07 NM_001288 TTC7A 1.91 0. 0. 163_chr1 955_chr2 8 0 1 8 0 5 2 NM_001 PTDSS1 8.297 0 0.03 NM_181886 UBE2D 1.69 0. 0. 290225_ _chr4 3 1 0 1 chr8 0 3 1 NM_000 PTGS2 1.472 0 0.03 NM_001076 UBTF 1.09 0 0. 963_chr1 684_chr17 9 0 7 NM_152 PTK7 6.975 0.0 0.11 NM_001284 UTP15 4.91 0 0. 882_chr6 01 431_chr5 2 0 7 NM_001 PTPRH 5.568 0.0 0.22 NR_047643 UTY 7.28 0. 0. 161440_ 04 _chrY 4 0 1 chr19 0 1 1 NM_002 PTX3 1.111 0 0.05 NM_001258 UTY 7.25 0. 0. 852_chr3 267_chrY 4 0 2 0 3 NM_001 PUM2 2.85 0 0.06 NR_073519 VPS51 2.59 0 0. 282752_ _chr11 1 0 chr2 2 NM_001 RABGEF1 6.534 0.0 0.12 NM_001289 VPS52 1.31 0. 0. 287061_ 01 176_chr6 6 0 2 chr7 0 3 NM_152 RASGEF1 1.258 0.0 0.11 NM_003401 XRCC4 21.7 0 0 545_chr4 B 01 _chr5 77 NR_1037 RCHY1 1.447 0 0.07 NM_023929 ZBTB1 4.94 0 0. 25_chr4 _chr8 0 2 0 6 NM_012 RERE 2.186 0.0 0.16 NM_144588 ZFYVE 7.81 0. 0. 102_chr1 02 _chr10 27 3 0 2 0 3 5 NM_014 RGCC 1.475 0.0 0.11 NM_001256 ZNF19 7.35 0. 0.

Downloaded From: https://jamanetwork.com/ on 09/28/2021 059_chr1 01 825_chr11 5 9 0 1 3 0 4 1 NM_001 RNGTT 6.939 0.0 0.24 NM_001242 ZNF32 6.70 0. 0. 286428_ 05 797_chr6 2 9 0 2 chr6 0 1 3 NR_1099 RP11- 1.491 0.0 0.22 NM_001079 ZNF33 7.16 0. 0. 46_chr5 260E18.1 04 907_chr19 1 0 1 0 6 2 NR_0497 RP11- 1.157 0.0 0.21 NM_001290 ZNF38 3.79 0 0. 93_chr6 356I2.4 04 002_chr12 5A 2 0 2 NM_001 RTN3 3.244 0.0 0.16 NM_007130 ZNF41 3.84 0 0. 265589_ 02 _chrX 0 chr11 2 NM_005 SERPINB 1.064 0.0 0.22 NM_152909 ZNF54 2.55 0. 0. 024_chr1 10 04 _chr19 8 9 0 2 8 0 3 eTable 1. DEGs of monocytes isolated from total ALS patients (vs. control) (continued 2) TransID Gene log2 p FDR TransID Gene log2 p F Name Fold value Name Fold v D Chan Chang al R ge e u e NM_017 ZNF56 1.491 0.004 0.22 NM_013232_ PDCD6 -1.594 0. 0. 656_chr1 2 chr5 0 1 9 0 9 3 NM_001 ZNF62 7.479 0.003 0.19 NM_0011647 PRKAR1 -8.119 0. 0. 290085_ 7 58_chr7 B 0 1 chr19 0 5 1 NR_1105 ZNF76 1.075 0.005 0.25 NM_024841_ PRR5L -1.074 0. 0. 51_chr19 1 chr11 0 1 0 5 1 NM_001 ZNF77 5.222 0.001 0.15 NM_004778_ PTGDR2 -1.143 0. 0. 024596_ 2 chr11 0 1 chr19 0 4 1 NM_000 ABCB1 -1.125 0.001 0.15 NM_0010136 PTX4 -1.358 0 0. 927_chr7 58_chr16 0 7 NM_213 ADAM -1.223 0.004 0.21 NM_0012044 RGS6 -5.846 0. 0. 604_chr1 TSL5 20_chr14 0 1 9 0 1 NR_0400 AP000 -1.549 0.004 0.21 NR_110616_ RP5- -1.026 0. 0. 84_chr21 688.14 chr1 1057J7.6 0 2 0 3 5

Downloaded From: https://jamanetwork.com/ on 09/28/2021 NM_004 AQP3 -1.654 0 0.05 NM_0011347 SARDH -1.588 0. 0. 925_chr9 07_chr9 0 1 0 9 3 NM_001 C10orf -1.224 0.001 0.14 NM_053282_ SH2D1B -1.394 0 0. 164375_ 105 chr1 0 chr10 5 NM_001 C12orf -6.77 0.001 0.13 NM_0011451 SHISA7 -2.952 0. 0. 286197_ 43 76_chr19 0 1 chr12 0 2 1 NM_152 C9orf6 -1.039 0.002 0.16 NM_138780_ SYTL5 -3.584 0 0. 833_chr9 9 chrX 0 8 NM_004 CA8 -1.285 0.005 0.25 NR_046327_ TRIM46 -4.331 0. 0. 056_chr8 chr1 0 2 0 3 5 NM_001 CCR7 -1.547 0.001 0.11 NM_053284_ WFIKKN -1.084 0. 0. 838_chr1 chr16 1 0 1 7 0 1 1 NM_001 CD27 -1.373 0 0.06 NM_0011711 ZBED1 -1.495 0 0. 242_chr1 35_chrX 0 2 8 NM_000 CD3G -1.834 0.001 0.11 NM_0010393 ZBTB7C -1.736 0. 0. 073_chr1 60_chr18 0 1 1 0 1 1 NM_004 CTDP1 -2.687 0.004 0.22 NM_0012817 ZMYND8 -4.905 0 0. 715_chr1 82_chr20 0 8 6 NM_001 DPYSL -6.847 0.001 0.12 NM_0010833 ZNF112 -2.408 0. 0. 197293_ 2 35_chr19 0 1 chr8 0 9 3 NM_001 ELP2 -1.658 0.003 0.2 NM_007153_ ZNF208 -1.347 0. 0. 242878_ chr19 0 2 chr18 0 2 4 NM_001 FAM21 -1.331 0.005 0.23 NR_073026_ ZNF334 -1.539 0. 0. 184945_ 9A chr20 0 1 chr9 0 8 2 NM_030 FCRL2 -1.367 0.004 0.21 764_chr1 NM_002 GATA3 -2.271 0 0.03 051_chr1 0 NM_005 GPR20 -1.419 0.003 0.19 293_chr8 NM_000 HBA1 -1.6 0.003 0.19 558_chr1 6 NM_000 HBB -2.065 0.002 0.17

Downloaded From: https://jamanetwork.com/ on 09/28/2021 518_chr1 1 NM_001 HIPK3 -1.249 0.002 0.16 048200_ chr11 NM_001 IFT122 -5.787 0.001 0.14 280546_ chr3 NM_144 IGJ -2.154 0 0.03 646_chr4 NM_181 IL21R -1.06 0.002 0.18 078_chr1 6 NM_002 IL7R -1.546 0.001 0.1 185_chr5 NM_021 JUP -1.118 0.004 0.22 991_chr1 7 NM_021 KCNJ1 -1.836 0.002 0.16 012_chr1 2 7 NM_015 KCTD2 -3.616 0 0 353_chr1 7 NM_152 KNDC1 -1.393 0 0.03 643_chr1 0 NM_001 LEFTY -2.858 0.003 0.19 172425_ 2 chr1 NR_0384 LINC0 -1.949 0.001 0.14 46_chr8 0861 NR_0384 LINC0 -2.82 0.002 0.17 47_chr8 0861 NM_001 MFSD2 -6.434 0.002 0.17 287809_ A chr1 NM_001 MMP2 -1.465 0 0.08 032278_ 8 chr17 NM_001 MYO3 -1.579 0.003 0.19 083615_ B chr2 NM_016 MZB1 -1.524 0.002 0.18 459_chr5 NM_005 NAALA -1.071 0 0.1 467_chr1 D2 1 NM_006 NMUR -2.562 0 0.06 056_chr2 1

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eTable 2. Disease progression of ALS patients for RNA-seq study based on a cutoff of 1.5 AALS points/month or a cutoff of 1 ALS FRS points/month Sample # AALS Slow/Fast ALS FRS Slow/Fast points/month based on points/month based on AALS ALS FRS

1 1.00 slow ALS 0.50 slow ALS 2 1.00 slow ALS 0.40 slow ALS 3 0.83 slow ALS 0.37 slow ALS 4 0.17 slow ALS 0.42 slow ALS 5 1.09 slow ALS 0.39 slow ALS 6 1.33 slow ALS 0.38 slow ALS 7 4.05 fast ALS 1.18 fast ALS 8 1.92 fast ALS 0.50 slow ALS 9 0.53 slow ALS 0.23 slow ALS 10 2.86 fast ALS 1.43 fast ALS 11 0.52 slow ALS 0.26 slow ALS 12 0.46 slow ALS 0.14 slow ALS 13 2.65 fast ALS 1.15 fast ALS 14 4.61 fast ALS 1.56 fast ALS 15 0.61 slow ALS 0.44 slow ALS 16 1.57 fast ALS 0.93 slow ALS 17 7.00 fast ALS 1.75 fast ALS 18 2.73 fast ALS 0.45 slow ALS 19 1.39 slow ALS 0.46 slow ALS 20 very late stage, could not judge slow/fast 21 1.48 slow ALS 1.75 fast ALS 22 -0.17 slow ALS 0.67 slow ALS 23 3.21 fast ALS 1.32 fast ALS

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eTable 3. 65 DEGs solely found in monocytes from slowly progressing ALS patients (vs. control) TransID Gene log2 p FD TransID Gene log2 p FD Name Fold val R Name Fold val R Cha ue Cha ue nge nge NR_028308_c BRE-AS1 1.65 0.0 0.2 NM_000054_c AVPR - 0.0 0.1 hr2 0 01 14 hrX 2 6.59 00 43 7 NM_005893_c CCIN 1.56 0.0 0.2 NM_152833_c C9orf - 0.0 0.0 hr9 3 01 17 hr9 69 1.42 00 56 1 NM_000742_c CHRNA2 3.40 0.0 0.2 NM_004715_c CTDP - 0.0 0.1 hr8 8 01 32 hr18 1 3.88 00 11 3 NM_00127647 CORO1C 4.87 0.0 0.0 NM_013976_c GCD - 0.0 0.2 1_chr12 5 00 83 hr19 H 6.18 02 45 7 NM_00119877 CUL2 2.28 0.0 0.2 NM_00104820 HIPK - 0.0 0.0 8_chr10 8 01 31 0_chr11 3 1.68 00 96 2 NM_004430_c EGR3 2.38 0.0 0.0 NM_024015_c HOX - 0.0 0.2 hr8 1 00 25 hr17 B4 1.01 01 14 6 NM_183004_c EIF5 1.08 0.0 0.0 NM_145249_c IFI27 - 0.0 0.1 hr14 1 00 88 hr14 L1 5.77 01 71 9 NM_005240_c ETV3 1.27 0.0 0.1 NM_00128054 IFT12 - 0.0 0.1 hr1 9 00 03 6_chr3 2 7.61 01 62 8 NM_015714_c G0S2 2.08 0.0 0.1 NM_002185_c IL7R - 0.0 0.1 hr1 4 01 96 hr5 1.74 01 71 3 NR_073568_c GHRLOS 7.32 0.0 0.1 NM_002343_c LTF - 0.0 0.0 hr3 4 00 53 hr3 21.2 00 00 44 NM_004893_c H2AFY 1.67 0.0 0.0 NM_002507_c NGF - 0.0 0.2 hr5 1 00 06 hr17 R 1.44 02 43 5 NR_038366_c HOTAIRM 2.14 0.0 0.0 NM_00120496 PBX1 - 0.0 0.0 hr7 1 4 00 11 3_chr1 7.34 00 25 3 NM_00119332 IKBKE 1.20 0.0 0.1 NR_028057_c PLCX - 0.0 0.2 2_chr1 9 01 62 hrX D1 2.30 01 22 2 NM_00128744 JADE1 1.23 0.0 0.2 NM_00101810 POLR - 0.0 0.1 0_chr4 7 01 14 2_chr15 2M 6.38 01 96 8 NR_047655_c KANSL3 2.51 0.0 0.1 NM_00124285 RNF1 - 0.0 0.2 hr2 5 01 85 0_chr6 46 1.12 02 43 8 NR_028138_c LINC0093 1.05 0.0 0.1 NM_005407_c SALL - 0.0 0.2 hr12 6 0 00 55 hr14 2 1.78 01 38

Downloaded From: https://jamanetwork.com/ on 09/28/2021 6 NR_024409_c LOC1001 5.12 0.0 0.2 NM_004263_c SEM - 0.0 0.0 hr3 28164 3 02 45 hr2 A4F 7.53 00 83 9 NM_00116157 MAFF 2.01 0.0 0.2 NM_021181_c SLAM - 0.0 0.1 3_chr22 3 01 38 hr1 F7 1.23 01 68 9 NM_182763_c MCL1 1.09 0.0 0.1 NM_00103495 SOR - 0.0 0.2 hr1 7 00 00 7_chr10 BS1 7.24 02 45 2 NM_00119070 MTRNR2 1.24 0.0 0.2 NM_00104027 SYCP - 0.0 0.0 2_chr11 L8 0 02 43 4_chr6 2L 4.06 00 23 0 NM_145638_c OSBPL5 3.49 0.0 0.2 NR_046327_c TRIM - 0.0 0.2 hr11 5 01 14 hr1 46 6.17 01 38 2 NM_00126780 PAAF1 2.60 0.0 0.2 NM_016258_c YTHD - 0.0 0.0 4_chr11 3 02 45 hr1 F2 1.11 00 36 2 NM_007350_c PHLDA1 1.66 0.0 0.2 hr12 2 01 38 NM_147163_c PSMG2 2.70 0.0 0.1 hr18 3 00 27 NM_00128706 RABGEF1 7.36 0.0 0.0 1_chr7 8 00 38 NM_00111349 SEPT9 2.12 0.0 0.1 4_chr17 6 00 21 NM_005024_c SERPINB 1.52 0.0 0.0 hr18 10 6 00 25 NM_152386_c SGPP2 1.20 0.0 0.1 hr2 9 00 41 NM_00120695 SLC16A3 1.80 0.0 0.1 2_chr17 0 00 03 NM_052901_c SLC25A2 1.15 0.0 0.1 hr9 5 2 00 24 NM_00118474 SLITRK4 3.78 0.0 0.1 9_chrX 7 01 85 NM_00117784 SRPR 1.15 0.0 0.2 2_chr11 6 02 43 NM_00117416 SYK 1.08 0.0 0.2 8_chr9 4 01 39 NM_00101363 TCTEX1D 1.02 0.0 0.2 2_chr1 4 7 02 45 NM_00128278 TRMU 2.37 0.0 0.1 4_chr22 1 00 55 NM_00128895 TTC7A 2.17 0.0 0.2 5_chr2 3 01 35 NM_00107668 UBTF 1.26 0.0 0.0 4_chr17 7 00 83 NM_00128443 UTP15 4.39 0.0 0.2 1_chr5 7 01 22 NR_073519_c VPS51 3.06 0.0 0.0 hr11 7 00 05 NM_007268_c VSIG4 1.04 0.0 0.2

Downloaded From: https://jamanetwork.com/ on 09/28/2021 hrX 1 02 47 NM_00129008 ZNF627 8.35 0.0 0.0 5_chr19 4 00 54 NM_00125736 AMPD2 - 0.0 0.0 0_chr1 1.55 00 72 4

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eTable 4. 237 DEGs solely found in monocytes from rapidly progressing ALS patients (vs. control) TransID Gene log2 p FDR TransID Gene log2 p F Name Fold valu Name Fold va D Chan e Change lu R ge e NM_001 AHR 1.017 0.001 0.09 NM_178232_c HAPLN3 1.527 0. 0. 621_chr 4 hr15 00 0 7 0 2 2 NM_001 ALCA 1.900 0.005 0.23 NM_177551_c HCAR2 1.247 0. 0. 243283_ M 5 hr12 00 1 chr3 1 0 3 NM_001 ALG1 1.371 0.003 0.18 NM_016323_c HERC5 1.165 0. 0. 168385_ 3 4 hr4 00 0 chrX 0 5 9 NM_144 ANKR 1.889 0.000 0.02 NM_003865_c HESX1 1.214 0. 0. 590_chr D22 3 hr3 00 1 10 1 1 3 NM_005 ANXA 1.862 0.004 0.20 NM_00116133 HIST2H2B 2.694 0. 0. 139_chr 3 7 4_chr1 F 00 2 4 5 3 6 NM_001 ARE 3.823 0.000 0.05 NM_021958_c HLX 1.087 0. 0. 657_chr G 5 hr1 00 0 4 0 6 3 NM_032 ARID 1.146 0.001 0.12 NM_005532_c IFI27 3.368 0. 0. 199_chr 5B 2 hr14 00 0 10 0 2 7 NM_212 ARL4 1.171 0.002 0.16 NM_006417_c IFI44 1.375 0. 0. 460_chr A 2 hr1 00 0 7 0 1 2 NM_001 ATF3 1.223 0.002 0.16 NM_006820_c IFI44L 1.647 0. 0. 030287_ 7 hr1 00 0 chr1 0 2 9 NM_001 ATP1 1.720 0.001 0.13 NM_022872_c IFI6 1.603 0. 0. 678_chr B2 4 hr1 00 0 17 0 1 3 NM_017 BAIA 7.625 0.003 0.18 NM_00127092 IFIT1 1.565 0. 0. 451_chr P2 1 9_chr10 00 0 17 0 5 2 NM_001 C6orf 4.080 0.004 0.21 NM_001547_c IFIT2 1.077 0. 0. 287397_ 1 4 hr10 00 1 chr6 4 9

Downloaded From: https://jamanetwork.com/ on 09/28/2021 8 NM_002 CCL2 1.936 0.000 0.06 NM_00103168 IFIT3 1.256 0. 0. 982_chr 5 3_chr10 00 1 17 2 6 3 NM_006 CCL7 3.122 0.005 0.23 NM_003641_c IFITM1 1.660 0. 0. 273_chr 7 hr11 00 0 17 0 4 0 NM_005 CCL8 1.984 0.001 0.13 NM_000600_c IL6 3.001 0. 0. 623_chr 5 hr7 00 0 17 0 5 9 NM_020 CD24 2.124 0.001 0.13 NM_176786_c IL9R 2.281 0. 0. 404_chr 8 4 hrX 00 2 11 5 3 5 NM_003 CH25 4.346 0.001 0.09 NM_005101_c ISG15 1.232 0. 0. 956_chr H 4 hr1 00 0 10 1 9 2 NR_046 CMP 1.301 0.000 0.01 NM_015907_c LAP3 1.114 0. 0. 236_chr K2 5 hr4 00 0 2 0 2 4 NM_001 CPEB 1.139 0.003 0.19 NM_005567_c LGALS3BP 1.066 0. 0. 177382_ 2 1 hr17 00 2 chr4 4 0 1 NM_152 CPT1 1.162 0.000 0.05 NM_00103180 LIMK2 1.124 0. 0. 245_chr B 3 1_chr22 00 0 22 0 1 0 NM_033 CSR 1.031 0.001 0.09 NR_038333_c LOC10050 1.719 0. 0. 027_chr NP1 5 hr5 5658 00 2 3 4 1 4 NM_005 CXCL 1.461 0.004 0.21 NM_052972_c LRG1 1.052 0. 0. 409_chr 11 1 hr19 00 1 4 1 0 4 NM_001 CYB5 2.860 0.004 0.20 NM_00112721 LY6E 1.013 0. 0. 134400_ 61D1 5 3_chr8 00 0 chr1 0 8 9 NM_004 DUSP 1.080 0.000 0.03 NM_00115964 MCTP2 1.684 0. 0. 417_chr 1 1 4_chr15 00 2 5 4 0 8 NM_003 DYSF 1.033 0.001 0.12 NM_00128780 MFSD2A 7.893 0. 0. 494_chr 2 8_chr1 00 0 2 0 7 9 NM_001 EMP1 1.670 0.000 0.06 NR_040073_c MIR181A1 2.037 0. 0. 423_chr 0 hr1 HG 00 1

Downloaded From: https://jamanetwork.com/ on 09/28/2021 12 1 1 3 NM_001 EPB4 1.022 0.000 0.06 NM_170739_c MRPL11 1.316 0. 0. 281533_ 1L3 5 hr11 00 1 chr18 1 1 0 NM_033 EPST 1.250 0.000 0.02 NR_028356_c MRPL30 1.498 0. 0. 255_chr I1 1 hr2 00 2 13 5 2 7 NM_004 ETV5 1.242 0.000 0.05 NM_002462_c MX1 1.014 0. 0. 454_chr 4 hr21 00 2 3 4 0 7 NM_001 ETV7 5.512 0.005 0.22 NM_014903_c NAV3 3.156 0. 0. 207035_ 7 hr12 00 1 chr6 1 0 4 NM_001 EXO 1.208 0.002 0.16 NM_00119962 NCOA7 1.250 0. 0. 013839_ C7 6 2_chr6 00 0 chr17 0 5 9 NM_001 FCG 1.211 0.000 0.05 NM_006403_c NEDD9 1.894 0. 0. 244910_ R1B 4 hr6 00 1 chr1 2 6 5 NM_005 FFAR 1.098 0.000 0.02 NM_00116616 NEK6 1.378 0. 0. 306_chr 2 7 7_chr9 00 1 19 1 3 0 NM_005 FFAR 1.778 0.001 0.12 NM_00125633 NKX3-1 3.911 0. 0. 304_chr 3 2 9_chr8 00 1 19 2 5 0 NM_001 FKBP 3.580 0.001 0.12 NM_00116611 NT5C3A 1.206 0. 0. 145776_ 5 8 8_chr7 00 1 chr6 2 6 1 NM_001 FLT1 2.193 0.002 0.13 NM_006187_c OAS3 1.033 0. 0. 160030_ 8 hr12 00 0 chr13 0 6 6 NM_024 FOXR 1.240 0.003 0.19 NM_003733_c OASL 1.136 0. 0. 955_chr ED2 0 hr12 00 0 22 0 6 4 NM_002 GBP1 1.020 0.003 0.19 NM_014279_c OLFM1 7.561 0. 0. 053_chr 7 hr9 00 2 1 5 3 5 NR_003 GBP1 1.822 0.002 0.16 NM_00100449 OR2B11 1.628 0. 0. 133_chr P1 5 2_chr1 00 0 1 0 7 4 NM_052 GBP5 1.575 0.000 0.04 NM_053001_c OSR2 2.719 0. 0.

Downloaded From: https://jamanetwork.com/ on 09/28/2021 942_chr 5 hr8 00 2 1 5 2 3 NM_001 GNA1 2.640 0.004 0.21 NM_00114537 OTUD1 1.043 0. 0. 282441_ 2 0 3_chr10 00 1 chr7 1 2 6 NM_001 GNAI 1.106 0.002 0.13 NM_002616_c PER1 1.461 0. 0. 282618_ 2 8 hr17 00 1 chr3 3 9 7 NM_170 GPR9 1.429 0.004 0.20 NM_00127157 PEX11A 7.569 0. 0. 776_chr 7 8 2_chr15 00 1 16 2 5 8 eTable 4. 237 DEGs solely found in monocytes from rapidly progressing ALS patients (vs. control) (continued 1) TransID Gene log2 p FDR TransID Gene log2 p F Name Fold valu Name Fold va D Chan e Change lu R ge e NM_00456 PFKFB3 1.674 0.00 0.11 NM_000927_c ABCB -1.217 0. 0. 6_chr10 1 3 hr7 1 00 2 5 3 5 NM_00124 PIM1 1.515 0.00 0.05 NM_213604_c ADAM -1.627 0. 0. 3186_chr6 0 4 hr19 TSL5 00 1 3 7 8 NM_00116 PTPRH 5.945 0.00 0.24 NM_00127841 AMN1 -7.442 0. 0. 1440_chr1 6 7 1_chr12 00 2 9 4 0 7 NM_00285 PTX3 1.323 0.00 0.03 NM_004925_c AQP3 -1.833 0. 0. 2_chr3 0 8 hr9 00 0 0 9 2 NM_00113 PUF60 1.621 0.00 0.18 NM_00127069 ARHG -6.566 0. 0. 6033_chr8 3 1 8_chr10 AP12 00 2 6 4 5 NM_00128 PUM2 3.156 0.00 0.07 NM_00128999 ATP6 -7.056 0. 0. 2752_chr2 0 4 0_chr7 V0E2 00 1 2 4 6 NM_15254 RASGE 1.399 0.00 0.12 NM_024603_c BEND -1.050 0. 0. 5_chr4 F1B 1 3 hr1 5 00 1 3 8 4 NM_01210 RERE 2.428 0.00 0.18 NM_003458_c BSN -1.391 0. 0. 2_chr1 3 4 hr3 00 1 3 7 3 NM_01405 RGCC 1.680 0.00 0.11 NR_038418_c BZRA -8.069 0. 0. 9_chr13 1 5 hr17 P1- 00 1

Downloaded From: https://jamanetwork.com/ on 09/28/2021 AS1 1 2 5 NM_01514 RGL1 1.420 0.00 0.01 NM_00116437 C10orf -1.841 0. 0. 9_chr1 0 0 5_chr10 105 00 0 0 2 1 NM_00119 RNF145 3.003 0.00 0.09 NM_145200_c CABP -1.068 0. 0. 9380_chr5 1 2 hr11 4 00 2 5 2 7 NR_10994 RP11- 1.784 0.00 0.17 NM_001242_c CD27 -1.698 0. 0. 6_chr5 260E18. 3 8 hr12 00 0 1 0 5 2 NR_04979 RP11- 1.418 0.00 0.16 NM_000073_c CD3G -1.977 0. 0. 3_chr6 356I2.4 2 5 hr11 00 1 3 8 9 NM_08065 RSAD2 1.430 0.00 0.08 NM_000074_c CD40 -1.139 0. 0. 7_chr2 0 1 hrX LG 00 2 5 3 5 NM_00513 SCO2 1.026 0.00 0.22 NM_00128673 CENP -1.340 0. 0. 8_chr22 5 7 4_chr4 E 00 1 1 2 6 NM_00299 SDC2 1.017 0.00 0.18 NR_047595_c CENP -7.057 0. 0. 8_chr8 3 7 hr13 J 00 2 5 3 6 NM_03210 SEMA6B 1.204 0.00 0.18 NM_007174_c CIT -1.427 0. 0. 8_chr19 3 2 hr12 00 2 6 4 2 NM_02306 SIGLEC 1.779 0.00 0.02 NM_001823_c CKB -1.514 0. 0. 8_chr20 1 0 3 hr14 00 0 0 1 5 NM_00116 SLC1A3 2.100 0.00 0.07 NM_001313_c CRMP -1.371 0. 0. 6696_chr5 0 4 hr4 1 00 2 5 3 9 NM_00128 SLC2A1 4.519 0.00 0.02 NM_00113575 DERL -5.244 0. 0. 6236_chr1 4 0 3 1_chr22 3 00 1 2 1 2 3 NM_00693 SLC2A3 1.241 0.00 0.05 NM_001935_c DPP4 -1.112 0. 0. 1_chr12 0 0 hr2 00 1 3 8 5 NM_00303 SLC2A5 1.233 0.00 0.23 NR_024075_c EMR4 -3.122 0. 0. 9_chr1 5 5 hr19 P 00 0 0 1 5 NM_00125 SLC8A1 1.925 0.00 0.19 NM_00114288 EPHX -1.249 0. 0.

Downloaded From: https://jamanetwork.com/ on 09/28/2021 2624_chr2 4 8 6_chr19 3 00 1 3 9 0 NR_04853 SLC9A8 2.826 0.00 0.02 NM_001996_c FBLN -3.255 0. 0. 8_chr20 0 3 hr22 1 00 1 3 8 1 NR_00354 SLED1 2.225 0.00 0.09 NM_000569_c FCGR -1.026 0. 0. 2_chr4 1 5 hr1 3A 00 2 5 3 0 NM_00128 SMG6 1.298 0.00 0.21 NM_00117181 GBA -7.010 0. 0. 2326_chr1 4 4 1_chr1 00 0 7 1 9 5 NM_00395 SOCS3 1.858 0.00 0.05 NM_001448_c GPC4 -1.036 0. 0. 5_chr17 0 5 hrX 00 0 0 8 2 NM_00584 SPRY1 7.980 0.00 0.19 NM_020155_c GPR1 -1.070 0. 0. 1_chr4 4 9 hr11 37 00 1 2 4 7 NM_17505 ST8SIA4 1.390 0.00 0.09 NM_207370_c GPR1 -1.210 0. 0. 2_chr5 0 2 hr1 53 00 1 1 2 5 NM_13881 TAGAP 1.153 0.00 0.09 NM_00126705 GPR1 -2.535 0. 0. 0_chr6 1 2 1_chr2 55 00 1 2 7 1 NM_00129 TIMM23 3.240 0.00 0.15 NM_005293_c GPR2 -2.124 0. 0. 0117_chr1 B 2 1 hr8 0 00 0 0 0 5 2 NM_03213 TKTL2 1.209 0.00 0.23 NM_00114577 GPR5 -7.191 0. 0. 6_chr4 5 5 1_chr16 6 00 2 6 4 2 NR_07350 TMEM39 1.129 0.00 0.17 NM_001512_c GSTA -1.781 0. 0. 6_chr3 A 3 6 hr6 4 00 0 0 6 2 NM_00127 TNFAIP 1.630 0.00 0.05 NM_00113068 GUCY -3.793 0. 0. 0508_chr6 3 0 8 5_chr4 1A3 00 1 2 6 6 NM_00116 TNFAIP 2.618 0.00 0.12 NM_012485_c HMM -5.964 0. 0. 7942_chr1 8L1 1 0 hr5 R 00 2 9 4 0 9 NM_00128 TRIB1 1.003 0.00 0.13 NM_152841_c HPS4 -4.680 0. 0. 2985_chr8 1 4 hr22 00 2 5 3 5

Downloaded From: https://jamanetwork.com/ on 09/28/2021 NM_00119 TRIQK 3.805 0.00 0.16 NM_00126787 HSD1 -4.175 0. 0. 1036_chr8 2 8 0_chr19 1B1L 00 1 1 2 2 NM_18188 UBE2D3 1.868 0.00 0.16 NM_002178_c IGFBP -1.771 0. 0. 6_chr4 2 1 hr12 6 00 1 1 0 3 NM_01741 USP18 1.754 0.00 0.03 NM_181078_c IL21R -1.353 0. 0. 4_chr22 0 8 hr16 00 1 1 0 4 NM_00116 ZBP1 1.108 0.00 0.09 NM_005546_c ITK -1.777 0. 0. 0418_chr2 0 1 hr5 00 1 0 3 8 6 NM_00344 ZNF155 8.646 0.00 0.04 NM_017625_c ITLN1 -1.026 0. 0. 5_chr19 0 7 hr1 00 0 1 9 2 NM_00125 ZNF195 7.608 0.00 0.19 NM_147152_c ITSN2 -7.734 0. 0. 6825_chr1 3 7 hr2 00 0 1 0 2 1 NM_01765 ZNF562 1.699 0.00 0.24 NM_004522_c KIF5C -1.340 0. 0. 6_chr19 6 0 hr2 00 0 1 9 5 eTable 4. 237 DEGs solely found in monocytes from rapidly progressing ALS patients (vs. control) (continued 2) TransID Gene log2 p FDR TransID Gene log2 p FDR Name Fold valu Name Fold valu Chan e Chan e ge ge NM_15264 KNDC - 0.00 0.00 NM_014767_c SPOC - 0.00 0.18 3_chr10 1 2.027 0 2 hr10 K2 1.527 3 4 NR_11090 LOC1 - 0.00 0.21 NM_00127858 ST13 - 0.00 0.18 9_chr16 01927 1.303 4 0 9_chr22 7.149 3 3 311 NR_02693 LOC1 - 0.00 0.10 NM_012447_c STAG - 0.00 0.19 4_chr3 52225 1.373 1 5 hr7 3 6.836 3 5 NR_03384 LOC2 - 0.00 0.10 NR_073071_c STRIP - 0.00 0.18 1_chr2 00772 1.369 1 3 hr1 1 8.073 3 7 NR_03398 LOC4 - 0.00 0.08 NM_016524_c SYT1 - 0.00 0.07 4_chr16 00548 1.238 0 1 hr16 7 1.213 0 9 NM_01483 LPPR - 0.00 0.20 NM_138780_c SYTL - 0.00 0.01 9_chr1 4 5.703 4 7 hrX 5 5.957 0 4 NM_00111 LRRC - 0.00 0.09 NM_00100287 THOC - 0.00 0.05 3567_chr1 75A 1.148 1 4 9_chr22 5 7.138 0 9 7 NM_17747 LYNX - 0.00 0.23 NM_00101092 TIAM2 - 0.00 0.09 6_chr8 1 1.165 5 4 7_chr6 1.420 1 4 NM_20554 LYPD - 0.00 0.02 NM_173799_c TIGIT - 0.00 0.19 5_chr8 2 2.161 0 4 hr3 2.727 3 6

Downloaded From: https://jamanetwork.com/ on 09/28/2021 NM_00116 MECO - 0.00 0.18 NM_007030_c TPPP - 0.00 0.16 4000_chr3 M 4.085 3 4 hr5 1.063 2 7 NM_00113 METT - 0.00 0.09 NM_015964_c TPPP - 0.00 0.01 5863_chr1 L20 5.213 1 5 hr16 3 1.238 0 2 2 NM_00103 MMP2 - 0.00 0.09 NR_030737_c TTC3 - 0.00 0.24 2278_chr1 8 1.958 1 5 hrX P1 1.213 6 4 7 NM_00114 MORF - 0.00 0.15 NM_00120004 TTC4 - 0.00 0.11 2432_chrX 4L2 5.665 2 1 9_chr10 0 2.231 1 1 NM_00119 MR1 - 0.00 0.12 NM_177987_c TUBB - 0.00 0.23 4999_chr1 6.784 1 1 hr10 8 4.742 5 3 NM_00108 MYO3 - 0.00 0.19 NM_181801_c UBE2 - 0.00 0.20 3615_chr2 B 2.094 3 7 hr20 C 3.142 4 9 NM_00499 MYO6 - 0.00 0.12 NM_182566_c VMO1 - 0.00 0.09 9_chr6 2.899 1 4 hr17 1.721 1 5 NM_00546 NAAL - 0.00 0.02 NM_053284_c WFIK - 0.00 0.05 7_chr11 AD2 1.484 0 4 hr16 KN1 1.560 0 3 NM_00113 NEDD - 0.00 0.02 NM_00117113 ZBED - 0.00 0.01 5175_chr1 1 5.592 0 3 5_chrX 1 2.158 0 3 2 NM_00114 NEDD - 0.00 0.19 NM_00103936 ZBTB - 0.00 0.05 4964_chr1 4L 5.859 3 5 0_chr18 7C 2.279 0 2 8 NM_00605 NMUR - 0.00 0.10 NM_00114544 ZNF2 - 0.00 0.20 6_chr2 1 2.961 1 6 8_chr16 00 3.112 4 7 NM_00125 PASK - 0.00 0.24 NM_00128864 ZNF2 - 0.00 0.14 2119_chr2 6.136 6 2 6_chr17 86A 6.955 2 7 NM_01891 PCDH - 0.00 0.19 NM_00128293 ZNF3 - 0.00 0.09 9_chr5 GA6 4.931 3 5 5_chr20 41 7.087 1 9 NM_00119 PHOS - 0.00 0.19 NM_033196_c ZNF6 - 0.00 0.11 9286_chr2 PHO2 5.879 3 5 hr19 82 4.106 1 7 NM_02090 PHRF - 0.00 0.13 1_chr11 1 2.243 1 5 NM_00264 PIK3C - 0.00 0.09 9_chr7 G 1.250 1 9 NM_00112 PLA2 - 0.00 0.20 8203_chr1 G16 1.135 4 8 1 NM_00112 PLEK - 0.00 0.21 9728_chr1 HG4 2.779 4 0 6 NM_00100 PLEK - 0.00 0.23 4330_chr1 HG7 1.964 5 2 2 NM_00127 PSMD - 0.00 0.18 8709_chr3 2 3.339 3 1 NR_10374 PTEN - 0.00 0.09 5_chr9 P1-AS 3.135 1 4 NM_00487 PTGE - 0.00 0.03 8_chr9 S 2.103 0 7 NM_00101 PTX4 - 0.00 0.06 3658_chr1 1.718 0 5 6 NM_00100 PUS1 - 0.00 0.20

Downloaded From: https://jamanetwork.com/ on 09/28/2021 2020_chr1 3.038 4 8 2 NM_02116 RAB4 - 0.00 0.19 8_chr16 0C 1.217 3 4 NM_17067 RASG - 0.00 0.15 2_chr2 RP3 6.954 2 4 NM_00120 RGS6 - 0.00 0.19 4420_chr1 6.505 3 5 4 NR_00293 SCAR - 0.00 0.05 4_chr10 T1 1.775 0 9 NM_05328 SH2D - 0.00 0.00 2_chr1 1B 2.055 0 2 NM_00114 SHIS - 0.00 0.19 5176_chr1 A7 3.303 3 0 9 NM_00116 SLC1 - 0.00 0.20 6496_chr1 6A1 6.326 4 2 NM_00108 SLC4 - 0.00 0.17 0397_chr1 5A1 1.276 2 2

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eTable 5. 43 DEGs expressed in monocytes of both slow and fast groups (vs. control) ALS Slow patients ALS fast patients TransID GeneName log2 p SLOW log2 p FAST Fold value FDR Fold value FDR Change Change NM_001242856_chr11 ARFIP2 8.067 0.000 0.032 6.910 0.001 0.092 NM_001251901_chr6 CD83 1.541 0.000 0.132 1.238 0.006 0.249 NM_001171933_chr10 CDH23 -5.401 0.002 0.246 -8.803 0.000 0.038 NM_001511_chr4 CXCL1 1.901 0.000 0.070 1.625 0.002 0.141 NM_002089_chr4 CXCL2 1.664 0.001 0.219 1.931 0.000 0.071 NM_001432_chr4 EREG 1.574 0.001 0.237 2.137 0.000 0.025 NM_001184945_chr9 FAM219A 2.831 0.000 0.048 -2.044 0.000 0.052 NM_133272_chr19 FCAR 4.064 0.000 0.024 1.978 0.000 0.048 NM_006732_chr19 FOSB 2.337 0.000 0.032 2.368 0.000 0.035 NM_005438_chr11 FOSL1 2.490 0.000 0.018 1.890 0.001 0.123 NM_002051_chr10 GATA3 -2.452 0.000 0.118 -2.079 0.002 0.167 NM_004951_chr13 GPR183 1.664 0.000 0.061 1.492 0.001 0.104 NM_001191013_chr10 GSTO2 5.546 0.002 0.243 5.172 0.004 0.210 NM_001945_chr5 HBEGF 1.987 0.000 0.056 1.602 0.002 0.166 NM_021034_chr11 IFITM3 -1.022 0.001 0.210 1.016 0.002 0.146 NM_144646_chr4 IGJ -2.410 0.000 0.034 -1.897 0.002 0.152 NM_000572_chr1 IL10 1.447 0.002 0.246 2.237 0.000 0.011 NM_000576_chr2 IL1B 1.598 0.002 0.242 1.579 0.003 0.180 NM_000584_chr4 IL8 1.912 0.000 0.083 1.808 0.001 0.095 NM_015353_chr17 KCTD2 -3.521 0.000 0.005 -3.738 0.000 0.010 NM_181986_chr19 LILRA5 2.283 0.001 0.219 2.211 0.002 0.171 NR_047524_chr1 LINC01128 8.123 0.001 0.207 8.063 0.001 0.134 NM_005746_chr7 NAMPT 1.021 0.001 0.191 1.227 0.000 0.050 NM_001258296_chr20 NFATC2 -5.573 0.000 0.081 -2.617 0.004 0.201 NM_005384_chr9 NFIL3 1.175 0.001 0.196 1.429 0.000 0.048 NM_006186_chr2 NR4A2 1.998 0.000 0.010 1.795 0.000 0.038 NM_198041_chr4 NUDT6 8.231 0.000 0.025 7.350 0.000 0.059 NM_020530_chr22 OSM 1.733 0.001 0.219 1.942 0.000 0.092 NM_001251855_chr17 PIK3R5 1.446 0.000 0.005 1.148 0.000 0.055 NM_004073_chr1 PLK3 1.006 0.002 0.249 1.040 0.002 0.161 NM_001290225_chr8 PTDSS1 8.024 0.000 0.083 8.568 0.000 0.041 NM_000963_chr1 PTGS2 1.669 0.000 0.039 1.195 0.005 0.238 NM_152882_chr6 PTK7 6.908 0.002 0.246 7.052 0.002 0.154 NR_103725_chr4 RCHY1 1.519 0.001 0.178 1.356 0.004 0.201 NM_001032295_chr11 SERPING1 -3.774 0.001 0.185 1.682 0.000 0.023 NM_001286115_chr1 THEMIS2 4.141 0.000 0.018 3.658 0.000 0.054

Downloaded From: https://jamanetwork.com/ on 09/28/2021 NM_021202_chr20 TP53INP2 1.653 0.000 0.010 1.195 0.001 0.124 NM_001242589_chr6 TREM1 1.531 0.000 0.004 1.324 0.000 0.023 NR_047643_chrY UTY 8.614 0.001 0.184 6.911 0.004 0.219 NM_003401_chr5 XRCC4 21.244 0.000 0.000 16.816 0.000 0.023 NM_001281782_chr20 ZMYND8 -5.842 0.001 0.159 -4.250 0.005 0.239 NM_001290002_chr12 ZNF385A 3.120 0.001 0.185 4.325 0.000 0.013 NM_007130_chrX ZNF41 3.901 0.000 0.057 3.764 0.000 0.064

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