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Home , Endonuclease, Guanylate kinase, Peptide deformylase

Table 3. GAS genes with negative or positive Z-scores (± 2.0 or higher) to SEGS values.

M5005_gene Gene Description Function Z(SEGS ) NFD(SEGS ) Phase Analysis Probe-set Probe M5005_Spy1423 - Hyaluronoglucosaminidase (EC 3.2.1.35) Phage -5.216330076 0.007485969 acute PPA1&2 SpM12_ChORF299-63_at 16 M5005_Spy0504 pepF Oligoendopeptidase F (EC 3.4.24.-) Amino acid metabolism -4.331206282 0.296785995 acute PPA1&2 SpM1_ChORF0606_s_at 10 M5005_Spy1186 - Phage protein Phage -4.323906633 0.305389038 acute PPA1&2 SpM1_ChORF1456_s_at 15 M5005_Spy0871 - Multidrug resistance ABC transporter ATP-binding and permease protein Membrane transport -4.320521915 0.309459061 acute PPA1&2 SpM1_ChORF1149_s_at 9 M5005_Spy0783 ptsD PTS system, mannose/fructose family IID component Carbohydrate metabolism -4.206162395 0.48212507 acute PPA1&2 SpM1_ChORF1060_s_at 13 M5005_Spy1466 - Phage protein Phage -4.196697521 0.499972759 acute PPA1&2 SpM12_ChORF299-14_at 12 M5005_Spy0868 - Hypothetical protein Unknown -4.1030198 0.714393283 acute PPA1&2 SpM1_ChORF1146_s_at 6 M5005_Spy0027 - IMP CYCLOHYDROLASE (EC 3.5.4.10) Nucleotide metabolism -4.042526536 0.897014541 acute PPA1&2 SpM18_ChORF0030_s_at 1 M5005_Spy1540 endoS Endo-beta-N-acetylglucosaminidase F2 precursor (EC 3.2.1.96) Carbohydrate metabolism -3.933430822 0.328559653 acute PPA3 SpM1_ChORF1813_at M5005_Spy0767 - 4-nitrophenylphosphatase (EC 3.1.3.41) Unknown -3.892686026 1.561207204 acute PPA1&2 SpM1_ChORF1043_s_at 12 M5005_Spy0680 - Two-component response regulator Signal transduction -3.858649146 1.767166565 acute PPA1&2 SpM1_ChORF0874_s_at 11 M5005_Spy1818 cadC Cadmium efflux system accessory protein Membrane transport -3.854956463 1.791005758 acute PPA1&2 SpM1_ChORF2163_s_at 6 M5005_Spy0135 - Hypothetical membrane associated protein Unknown -3.775054045 2.38833708 acute PPA1&2 SpM1_ChORF0159_s_at 4 M5005_Spy0101 adhE tRNA binding domain protein Protein synthesis -3.762426541 0.621439274 acute PPA3 SpM18_ChORF0118_s_at M5005_Spy0517 regR Transcriptional regulator, LacI family Information processing -3.718295416 2.922851942 acute PPA1&2 SpM1_ChORF0627_s_at 12 M5005_Spy0537 aspC Aspartate aminotransferase (EC 2.6.1.1) Amino acid metabolism -3.713735557 2.97039385 acute PPA1&2 SpM1_ChORF0650_s_at 12 M5005_Spy0850 pta putative phosphotransacetylase Cellular processing -3.712057722 2.988071055 acute PPA1&2 SpM1_ChORF1128_s_at 2 M5005_Spy0539 - ATP-binding protein (contains P-loop) Membrane transport -3.706946834 3.042534595 acute PPA1&2 SpM1_ChORF0652_s_at 12 M5005_Spy0061 rpsE SSU ribosomal protein S5P Protein synthesis -3.564877715 4.992516532 acute PPA1&2 SpM1_ChORF0069_s_at 1 M5005_Spy0780 - PTS system, mannose/fructose family IIA component Unknown -3.558956355 5.095166371 acute PPA1&2 SpM1_ChORF1057_s_at 4 M5005_Spy1222 int.2 DNA integration/recombination/invertion protein phi5005.2 int Phage -3.528292626 1.437858399 acute PPA3 SpM1_ChORF1488_s_at M5005_Spy1663 - PTS SYSTEM, IIB COMPONENT (EC 2.7.1.69) Carbohydrate metabolism -3.518197772 1.489487779 acute PPA3 SpM1_ChORF1950_s_at M5005_Spy0868 - Hypothetical protein Unknown -3.498271411 6.268403115 acute PPA1&2 SpM1_ChORF1146_s_at 13 M5005_Spy0681 - Two component system histidine (EC 2.7.3.-) Signal transduction -3.470882902 6.877391164 acute PPA1&2 SpM1_ChORF0875_s_at 10 M5005_Spy1654 - Hypothetical protein Unknown -3.466760567 1.780738647 acute PPA3 SpM5_ChORF125g-139_at M5005_Spy0058 rpsH SSU ribosomal protein S8P Protein synthesis -3.453323491 7.296659007 acute PPA1&2 SpM1_ChORF0065_s_at 2 M5005_Spy0764 - Hypothetical protein Unknown -3.451868835 7.332449053 acute PPA1&2 SpM1_ChORF1039_s_at 2 M5005_Spy1685 - D-tyrosyl-tRNA(Tyr) deacylase (EC 3.1.-.-) Protein synthesis -3.432458086 7.826096765 acute PPA1&2 SpyM3_1699_at 15 M5005_Spy1412 nusA N utilization substance protein A Cellular processing -3.424128817 8.047355927 acute PPA1&2 SpM1_ChORF1724_s_at 4 M5005_Spy1695 - Ribosomal protein L11 (EC 2.1.1.-) Protein synthesis -3.38737853 2.336928839 acute PPA3 SpM1_ChORF1988_s_at M5005_Spy1184 - Phage protein Phage -3.380925254 9.292393133 acute PPA1&2 SpM1_ChORF1455_s_at 2 M5005_Spy1519 recG ATP-dependent DNA recG (EC 3.6.1.-) Information processing -3.35546511 10.10845036 acute PPA1&2 SpM1_ChORF1785_s_at 4 M5005_Spy1052 int.1 DNA integration/recombination/invertion protein phi5005.1 int Phage -3.338082749 2.760149795 acute PPA3 SpM18_ChORF1309_s_at M5005_Spy0384 - Surface antigen Virulence -3.311211515 11.68868554 acute PPA1&2 SpM1_ChORF0469_s_at 9 M5005_Spy0466 - Hypothetical phage protein Phage -3.303624186 11.98180002 acute PPA1&2 SpM18_ChORF0632_s_at 13 M5005_Spy1083 - Transcription antiterminator, BglG family / PTS system, mannitol (Cryptic)-specific IIA component (EC 2.7.1.69) Information processing -3.287297784 12.63598108 acute PPA1&2 SpM1_ChORF1325_s_at 12 M5005_Spy1331 - Peptidyl-prolyl cis-trans (EC 5.2.1.8) Unknown -3.285825973 3.286280558 acute PPA3 SpM12_ChORF289-26_at M5005_Spy0834 - Zn-dependent dehydrogenases and related dehydrogenases Unknown -3.28182996 12.86242904 acute PPA1&2 SpM1_ChORF1111_s_at 14 M5005_Spy0223 - GTPase (EC 3.6.1.-) Unknown -3.275939861 13.11060343 acute PPA1&2 SpM1_ChORF0263_s_at 2 M5005_Spy1245 - RNA binding protein Unknown -3.275245713 3.403597214 acute PPA3 SpM1_ChORF1515_s_at M5005_Spy1117 deaD2 ATP-dependent RNA helicase Stress -3.240898929 14.68188904 acute PPA1&2 SpM1_ChORF1369_s_at 8 M5005_Spy0962 - Hypothetical protein Unknown -3.22528854 15.43697381 acute PPA1&2 SpM1_ChORF1252_s_at 7 M5005_Spy0318 pflC Pyruvate formate- activating (EC 1.97.1.4) Carbohydrate metabolism -3.193399082 17.09327816 acute PPA1&2 SpM1_ChORF0379_s_at 1 M5005_Spy0066 infA Bacterial Protein Translation Initiation Factor 1 (IF-1) Cellular processing -3.167588232 18.55343013 acute PPA1&2 SpM1_ChORF0075_s_at 3 M5005_Spy0058 rpsH SSU ribosomal protein S8P Protein synthesis -3.166716579 18.60470802 acute PPA1&2 SpM1_ChORF0065_s_at 15 M5005_Spy0587 pheS Phenylalanyl-tRNA synthetase alpha chain (EC 6.1.1.20) Protein synthesis -3.165720561 4.869546395 acute PPA3 SpM1_ChORF0768_s_at M5005_Spy1386 - Hypothetical membrane spanning protein Unknown -3.163061351 4.911525008 acute PPA3 SpM1_ChORF1691_s_at M5005_Spy0121 - Acetyl-CoA:acetoacetyl-CoA beta subunit (EC 2.8.3.-) Carbohydrate metabolism -3.153036204 19.42695837 acute PPA1&2 SpM1_ChORF0142_s_at 1 M5005_Spy0264 - (HAD superfamily) Unknown -3.1418665 20.12321039 acute PPA1&2 SpM1_ChORF0309_s_at 9 M5005_Spy1077 glnQ.2 Glutamine transport ATP-binding protein glnQ Membrane transport -3.139799861 20.25454571 acute PPA1&2 SpM1_ChORF1316_s_at 2 M5005_Spy1140 queA S-adenosylmethionine:tRNA ribosyltransferase-isomerase (EC 5.-.-.-) Protein synthesis -3.136894369 20.44053681 acute PPA1&2 SpM1_ChORF1400_s_at 3 M5005_Spy0057 rpsN SSU ribosomal protein S14P Protein synthesis -3.113849697 21.97284948 acute PPA1&2 SpM1_ChORF0064_s_at 5 M5005_Spy1581 - Transcriptional regulator, MerR family Information processing -3.108428234 22.34849834 acute PPA1&2 SpM1_ChORF1863_s_at 10 M5005_Spy0291 - Acetyltransferase (GNAT) family Unknown -3.093317946 23.42713531 acute PPA1&2 SpM1_ChORF0346_s_at 10 M5005_Spy1162 - Hypothetical protein Unknown -3.065782387 25.51771239 acute PPA1&2 SpM1_ChORF1425_s_at 14 M5005_Spy1442 - Phage transcriptional activator Phage -3.048812964 7.066038664 acute PPA3 SpM12_ChORF299-47_s_at M5005_Spy1163 - Transcriptional regulator, biotin repressor family Information processing -3.045289397 27.18423637 acute PPA1&2 SpM1_ChORF1427_s_at 2 M5005_Spy0399 - Hypothetical membrane associated protein Unknown -3.031029316 7.470938877 acute PPA3 SpM1_ChORF0484_s_at M5005_Spy1753 pbp2A Multimodular transpeptidase-transglycosylase PBP 2A Cell wall metabolism -3.016868338 29.66235776 acute PPA1&2 SpM1_ChORF2059_s_at 10 M5005_Spy0517 regR Transcriptional regulator, LacI family Information processing -3.015397193 7.844402513 acute PPA3 SpM1_ChORF0627_at M5005_Spy0038 - Acyltransferase family Unknown -3.00540974 30.71921048 acute PPA1&2 SpM1_ChORF0041_s_at 9 M5005_Spy1064 malC Maltose transport system permease protein malF Membrane transport -3.002107449 31.03017584 acute PPA1&2 SpM1_ChORF1301_at 10 M5005_Spy1235 - PHOSPHOGLUCOMUTASE (EC 5.4.2.2) / PHOSPHOMANNOMUTASE (EC 5.4.2.8) Carbohydrate metabolism -2.98473965 8.627219281 acute PPA3 SpM1_ChORF1503_s_at M5005_Spy1184 - Phage protein Phage -2.924566748 10.37627195 acute PPA3 SpM3_ChORF1109_x_at M5005_Spy0338 - Arsenate reductase family protein Unknown -2.870606323 12.21526168 acute PPA3 SpM1_ChORF0410_s_at M5005_Spy1000 - Phage protein Phage -2.866123237 12.38072212 acute PPA3 SpM49_ChORF7585-41_at

Page 1 of 8 Table 3. GAS genes with negative or positive Z-scores (± 2.0 or higher) to SEGS values.

M5005_gene Gene Description Function Z(SEGS ) NFD(SEGS ) Phase Analysis Probe-set Probe M5005_Spy0225 - Thiamin pyrophosphokinase (EC 2.7.6.2) Coenzyme and metabolism -2.801086386 15.02283823 acute PPA3 SpM1_ChORF0265_s_at M5005_Spy0305 - putative phosphoesterase Unknown -2.796292302 15.23659114 acute PPA3 SpM1_ChORF0363_s_at M5005_Spy0242 - ABC transporter ATP-binding protein Coenzyme and cofactor metabolism -2.792643857 15.40111464 acute PPA3 SpM1_ChORF0285_s_at M5005_Spy0824 folK 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase (EC 2.7.6.3) Coenzyme and cofactor metabolism -2.790890806 15.48074054 acute PPA3 SpM1_ChORF1100_s_at M5005_Spy0374 rplK LSU ribosomal protein L11P Protein synthesis -2.756988778 17.09613356 acute PPA3 SpM1_ChORF0460_s_at M5005_Spy1450 - PHAGE-RELATED DNA (EC 2.7.7.7) Phage -2.734810007 18.23421574 acute PPA3 SpM5_ChORF4P31a-205_at M5005_Spy0038 - Acyltransferase family Unknown -2.723236166 18.85500706 acute PPA3 SpM1_ChORF0041_s_at M5005_Spy0806 srtA Lantibiotic srtA precursor Virulence -2.695031659 20.44879481 acute PPA3 SpM1_ChORF1083_at M5005_Spy0976 - Integral membrane protein Unknown -2.686199401 20.97238219 acute PPA3 SpM1_ChORF1265_s_at M5005_Spy1731 - Hypothetical cytosolic protein Unknown -2.667012033 22.15181825 acute PPA3 SpM18_ChORF2095_s_at M5005_Spy0358 - Hypothetical protein Unknown -2.665695732 22.23488465 acute PPA3 SpM12_ChORF212-2_s_at M5005_Spy1668 - Putative transcriptional regulator Unknown -2.628304492 24.71509041 acute PPA3 SpM1_ChORF1957_s_at M5005_Spy0092 - ComG operon protein 6 Unknown -2.607211065 26.22165711 acute PPA3 SpM1_ChORF0107_s_at M5005_Spy0519 agaD PTS system, N-acetylgalactosamine-specific IID component (EC 2.7.1.69) Carbohydrate metabolism -2.594229656 27.18939387 acute PPA3 SpM1_ChORF0629_s_at M5005_Spy1313 - Beta-glucosidase (EC 3.2.1.21) Carbohydrate metabolism -2.543027924 31.32678133 acute PPA3 SpM1_ChORF1599_s_at M5005_Spy0983 - Histidine transport ATP-binding protein hisP Membrane transport -2.458745105 39.37436375 acute PPA3 SpM1_ChORF1275_s_at M5005_Spy1390 - Hypothetical protein Unknown -2.454879477 39.78405968 acute PPA3 SpM1_ChORF1697_s_at M5005_Spy1735 speB Streptococcal pyrogenic exotoxin B (EC 3.4.22.10) Virulence -2.444627435 40.88902601 acute PPA3 SpM1_ChORF2039_s_at M5005_Spy0790 gabD Succinate-semialdehyde dehydrogenase [NADP+] (EC 1.2.1.16) Carbohydrate metabolism -2.406229852 45.27359808 acute PPA3 SpM1_ChORF1067_s_at M5005_Spy1602 - Predicted kinase related to hydroxyacetone kinase Unknown -2.403014292 45.65901617 acute PPA3 SpM1_ChORF1885_s_at M5005_Spy1598 - Hypothetical protein Unknown -2.362145502 50.81662548 acute PPA3 SpM1_ChORF1879_s_at M5005_Spy1811 - Hypothetical membrane spanning protein Unknown -2.347730772 52.75471893 acute PPA3 SpM1_ChORF2155_s_at M5005_Spy0274 braB Branched-chain amino acid transport system carrier protein Membrane transport -2.341002906 53.68137832 acute PPA3 SpM5_ChORFJ7578C-342_s_at M5005_Spy1065 amyA Alpha-amylase (EC 3.2.1.1) Carbohydrate metabolism -2.33500479 54.51957917 acute PPA3 SpM1_ChORF1302_at M5005_Spy0144 - Hypothetical protein Unknown -2.32883577 55.39365589 acute PPA3 SpM3_ChORF0132_x_at M5005_Spy1454 - Phage protein Phage -2.296892132 60.11963604 acute PPA3 SpM12_ChORF299-39_s_at M5005_Spy1782 pepO Neutral endopeptidase (EC 3.4.24.-) Cellular processing -2.292767759 60.75490099 acute PPA3 SpM5_ChORF125g-225_at M5005_Spy1282 msrA Peptide methionine sulfoxide reductase msrA/msrB (EC 1.8.4.6) Cellular processing -2.285943723 61.81891393 acute PPA3 SpM1_ChORF1557_s_at M5005_Spy0383 - D-alanyl-D-alanine carboxypeptidase (EC 3.4.16.4) Cell wall metabolism -2.270076234 64.3563134 acute PPA3 SpM1_ChORF0467_s_at M5005_Spy0787 - Hypothetical protein Unknown -2.254247938 66.97774436 acute PPA3 SpM1_ChORF1064_at M5005_Spy0106 rofA Transcriptional regulator Information processing -2.243322477 68.84114966 acute PPA3 SpM1_ChORF0124_s_at M5005_Spy0803 srtI protein involved in lantibiotic (srt) production Virulence -2.222129677 72.58500161 acute PPA3 SpM1_ChORF1080_s_at M5005_Spy1264 - Ribose operon repressor Information processing -2.222051962 72.59905032 acute PPA3 SpM1_ChORF1535_s_at M5005_Spy1213 - Phage protein Phage -2.221953432 72.61686549 acute PPA3 SpM3_ChORF0967_at M5005_Spy1858 trsA/trpA Tryptophanyl-tRNA synthetase (EC 6.1.1.2) Protein synthesis -2.211054114 74.61119725 acute PPA3 SpM1_ChORF2207_s_at M5005_Spy0441 aroE.2 Shikimate 5-dehydrogenase (EC 1.1.1.25) Amino acid metabolism -2.178767466 80.80094352 acute PPA3 SpM1_ChORF0534_s_at M5005_Spy1789 nrdG Anaerobic ribonucleoside-triphosphate reductase activating protein (EC 1.97.1.4) Cellular processing -2.170548327 82.44599618 acute PPA3 SpM1_ChORF2105_s_at M5005_Spy0408 fpg Formamidopyrimidine-DNA glycosylase (EC 3.2.2.23) Information processing -2.168053912 82.95095395 acute PPA3 SpM1_ChORF0497_s_at M5005_Spy0180 - S-layer homology domain / Putative murein endopeptidase Unknown -2.166221244 83.32365489 acute PPA3 SpM1_ChORF0210_s_at M5005_Spy1829 - Phage infection protein Phage -2.125644672 91.95476538 acute PPA3 SpM1_ChORF2176_s_at M5005_Spy0369 mtsB Manganese transport system ATP-binding protein mntA Membrane transport -2.125491099 91.98884339 acute PPA3 SpM1_ChORF0454_s_at M5005_Spy0206 fasA Response regulator FasA Signal transduction -2.123129544 92.51424882 acute PPA3 SpM1_ChORF0245_s_at M5005_Spy0322 fhuB Ferrichrome transport system permease protein fhuB Membrane transport -2.115730272 94.17723347 acute PPA3 SpM1_ChORF0384_s_at M5005_Spy0828 potC Spermidine/putrescine transport system permease protein potC Membrane transport -2.10894706 95.72430359 acute PPA3 SpM5_ChORF270b-433_s_at M5005_Spy0821 folE GTP cyclohydrolase I (EC 3.5.4.16) Coenzyme and cofactor metabolism -2.093068544 99.43147645 acute PPA3 SpM1_ChORF1097_s_at M5005_Spy1158 ddlA D-alanine--D-alanine (EC 6.3.2.4) Cell wall metabolism -2.081206158 102.2808409 acute PPA3 SpM1_ChORF1421_s_at M5005_Spy1238 - Arginine transport system permease protein artQ Membrane transport -2.07238694 104.4443515 acute PPA3 SpM1_ChORF1507_s_at M5005_Spy1590 rpsN2 SSU ribosomal protein S14P Protein synthesis -2.071844201 104.578766 acute PPA3 SpM1_ChORF1871_s_at M5005_Spy1289 - Hypothetical protein Unknown -2.054752476 108.8881468 acute PPA3 SpM1_ChORF1565_s_at M5005_Spy1800 cinA Colligrin Information processing -2.04544449 111.298202 acute PPA3 SpM1_ChORF2117_s_at M5005_Spy1037 - Phage single-strand DNA binding protein Phage -2.043784368 111.7327983 acute PPA3 SpM18_ChORF1795_s_at M5005_Spy0759 - Hypothetical membrane associated protein Unknown -2.04133778 112.3759207 acute PPA3 SpM12_ChORF281-3_at M5005_Spy1485 accA Acetyl-coenzyme A carboxylase carboxyl transferase subunit beta (EC 6.4.1.2) Lipid metabolism -2.038090511 113.2343914 acute PPA3 SpM1_ChORF1743_s_at M5005_Spy1341 gmk Guanylate kinase (EC 2.7.4.8) Nucleotide metabolism -2.028388958 115.8325599 acute PPA3 SpM1_ChORF1632_s_at M5005_Spy1565 spi Signal peptidase I (EC 3.4.21.89) Cellular processing -2.027299738 116.1274107 acute PPA3 SpM1_ChORF1842_s_at M5005_Spy1677 - Protein subunit YajC Secretion -2.026771016 116.2707656 acute PPA3 SpM1_ChORF1968_s_at M5005_Spy0219 - Transcriptional regulator, RpiR family Cellular processing -2.021614814 117.6767125 acute PPA3 SpM1_ChORF0259_s_at M5005_Spy1823 - Integral membrane protein Phage -2.019282157 118.3175004 acute PPA3 SpM1_ChORF2169_s_at M5005_Spy0645 - ABC transporter ATP-binding protein Membrane transport -2.015300516 119.4181305 acute PPA3 SpM1_ChORF0837_s_at M5005_Spy0636 epuA Transcriptional regulators, LysR family Information processing -2.012393013 120.2273325 acute PPA3 SpM18_ChORF0886_s_at M5005_Spy1252 murG UDP-N-acetylglucosamine:lipid I N-acetylglucosaminyltransferase Cellular processing -2.003050941 122.859004 acute PPA3 SpM1_ChORF1524_s_at M5005_Spy0487 - Hypothetical exported protein Unknown -2.002391506 123.0466024 acute PPA3 SpM1_ChORF0588_s_at M5005_Spy0373 - Integral membrane protein Unknown 4.855757116 0.035220672 acute PPA1&2 SpM1_ChORF0459_s_at 4 M5005_Spy0865 - SUA5 protein Information processing 4.825243953 0.00860861 acute PPA3 SpM1_ChORF1143_s_at M5005_Spy1442 - Phage transcriptional activator Phage 4.787877581 0.046797121 acute PPA1&2 SpM12_ChORF299-47_s_at 1 M5005_Spy0506 ftsW Cell division protein ftsW Cellular processing 4.032964464 0.929688747 acute PPA1&2 SpM1_ChORF0609_s_at 3

Page 2 of 8 Table 3. GAS genes with negative or positive Z-scores (± 2.0 or higher) to SEGS values.

M5005_gene Gene Description Function Z(SEGS ) NFD(SEGS ) Phase Analysis Probe-set Probe M5005_Spy0245 nifU, yurV IscU protein Coenzyme and cofactor metabolism 3.96883563 1.180083659 acute PPA1&2 SpM1_ChORF0289_s_at 2 M5005_Spy1792 - Hypothetical protein Unknown 3.922936612 1.397539785 acute PPA1&2 SpM18_ChORF2167_x_at 14 M5005_Spy1215 - Phage protein Phage 3.876472084 1.656290999 acute PPA1&2 SpM1_ChORF0948_s_at 5 M5005_Spy0932 - Luciferase-like monooxygenase (EC 1.14.-.-) Unknown 3.852674993 1.805887095 acute PPA1&2 SpM1_ChORF1219_s_at 16 M5005_Spy0114 - Sortase Cell wall metabolism 3.837522693 1.907748107 acute PPA1&2 SpM12_ChORF300-50_s_at 11 M5005_Spy0913 - /recombinase xerD Phage 3.824863765 1.997015582 acute PPA1&2 SpM1_ChORF1196_s_at 15 M5005_Spy0218 - N-acetylmannosamine kinase (EC 2.7.1.60) / Transcriptional regulator Carbohydrate metabolism 3.760220444 2.518289808 acute PPA1&2 SpM1_ChORF0258_s_at 13 M5005_Spy0134 - Tellurite resistance protein Unknown 3.679076719 3.356470665 acute PPA1&2 SpM1_ChORF0158_s_at 9 M5005_Spy0445 metK S-adenosylmethionine synthetase (EC 2.5.1.6) Cellular processing 3.656932869 3.62752722 acute PPA1&2 SpM1_ChORF0538_s_at 5 M5005_Spy0693 - Hypothetical protein Unknown 3.641313256 3.831045618 acute PPA1&2 SpM1_ChORF0887_s_at 11 M5005_Spy1854 - Hypothetical cytosolic protein Cellular processing 3.621533812 1.034390958 acute PPA3 SpM1_ChORF2203_s_at M5005_Spy0677 fms Peptide deformylase (EC 3.5.1.88) Information processing 3.585355298 4.652371784 acute PPA1&2 SpM1_ChORF0870_s_at 6 M5005_Spy0128 ntpE V-type sodium ATP synthase subunit E (EC 3.6.3.14) Membrane transport 3.525461656 5.714324726 acute PPA1&2 SpM1_ChORF0150_s_at 3 M5005_Spy0201 - Carbonic anhydrase (EC 4.2.1.1) Unknown 3.520738483 1.476331822 acute PPA3 SpM1_ChORF0237_s_at M5005_Spy1248 - Pyridoxal-5'-phosphate family protein Unknown 3.493810089 6.364011408 acute PPA1&2 SpM1_ChORF1519_s_at 2 M5005_Spy0581 atpD ATPase, beta subunit Carbohydrate metabolism 3.454535045 7.266975627 acute PPA1&2 SpM12_ChORF269-12_s_at 13 M5005_Spy0747 - Zn-dependent hydrolase (EC 3.-.-.-) Unknown 3.423578455 8.062180791 acute PPA1&2 SpM1_ChORF1020_s_at 5 M5005_Spy0521 agaV PTS system, N-acetylgalactosamine-specific IIB component (EC 2.7.1.69) Carbohydrate metabolism 3.412985769 8.352557372 acute PPA1&2 SpM1_ChORF0631_s_at 9 M5005_Spy0212 - N-acetylmannosamine-6-phosphate 2-epimerase (EC 5.1.3.9) Carbohydrate metabolism 3.412363414 8.369919751 acute PPA1&2 SpM1_ChORF0251_s_at 9 M5005_Spy0694 clpL ATP-dependent protease ATP-binding subunit clpL Stress 3.411967126 2.149298157 acute PPA3 SpM1_ChORF0888_s_at M5005_Spy0720 - putative exfoliative toxin Virulence 3.411902921 8.382788324 acute PPA1&2 SpM12_ChORF248-9_s_at 13 M5005_Spy1215 - Phage protein Phage 3.409735415 8.443609572 acute PPA1&2 SpM1_ChORF0948_s_at 3 M5005_Spy0224 rpe Ribulose-phosphate 3-epimerase (EC 5.1.3.1) Carbohydrate metabolism 3.397789778 8.786309554 acute PPA1&2 SpM1_ChORF0264_s_at 2 M5005_Spy0602 rmlD dTDP-4-dehydrorhamnose reductase (EC 1.1.1.133) Cell wall metabolism 3.392115357 8.953632318 acute PPA1&2 SpM1_ChORF0784_s_at 11 M5005_Spy1049 - Phage protein Phage 3.366370889 9.750999338 acute PPA1&2 SpM18_ChORF1305_s_at 16 M5005_Spy1339 priA Primosomal protein N' Information processing 3.341979703 10.56742932 acute PPA1&2 SpM1_ChORF1629_s_at 11 M5005_Spy0571 - // family protein Unknown 3.289387272 3.247647467 acute PPA3 SpM1_ChORF0747_s_at M5005_Spy1025 - Phage encoded transcriptional regulator, ArpU family Phage 3.286908109 12.65199522 acute PPA1&2 SpM1_ChORF0677_s_at 13 M5005_Spy0762 - Hypothetical membrane associated protein Unknown 3.273711341 13.20566087 acute PPA1&2 SpM1_ChORF1037_s_at 1 M5005_Spy1208 - Phage protein Phage 3.27150828 3.445963259 acute PPA3 SpM18_ChORF0727_x_at M5005_Spy0094 ackA (EC 2.7.2.1) Carbohydrate metabolism 3.234297265 14.99691268 acute PPA1&2 SpM1_ChORF0109_s_at 14 M5005_Spy1146 - DNA polymerase III, delta subunit (EC 2.7.7.7) Information processing 3.231214322 15.1461757 acute PPA1&2 SpM12_ChORF213-4_s_at 6 M5005_Spy0928 lplA Lipoate-protein ligase A (EC 6.-.-.-) Coenzyme and cofactor metabolism 3.203478912 16.55266137 acute PPA1&2 SpM1_ChORF1214_s_at 10 M5005_Spy1304 lacZ Beta-galactosidase (EC 3.2.1.23) Carbohydrate metabolism 3.196845378 16.90661889 acute PPA1&2 SpM1_ChORF1586_s_at 2 M5005_Spy0685 - Isopentenyl-diphosphate delta-isomerase (EC 5.3.3.2) Lipid metabolism 3.194230129 17.04809207 acute PPA1&2 SpM1_ChORF0879_s_at 16 M5005_Spy1726 - ABC transporter permease protein Membrane transport 3.184109473 17.60602146 acute PPA1&2 SpM1_ChORF2029_s_at 8 M5005_Spy1411 - Hypothetical cytosolic protein Unknown 3.16239352 18.86097917 acute PPA1&2 SpM1_ChORF1722_s_at 9 M5005_Spy0065 (EC 2.7.4.3) Cellular processing 3.155811183 19.25748836 acute PPA1&2 SpM1_ChORF0074_s_at 13 M5005_Spy0049 rplV LSU ribosomal protein L22P Protein synthesis 3.146057893 19.85927157 acute PPA1&2 SpM1_ChORF0055_s_at 7 M5005_Spy0677 fms Peptide deformylase (EC 3.5.1.88) Information processing 3.145902057 19.86902694 acute PPA1&2 SpM1_ChORF0870_s_at 16 M5005_Spy1108 metK S-adenosylmethionine synthetase (EC 2.5.1.6) Cellular processing 3.136995164 20.43405804 acute PPA1&2 SpM1_ChORF1359_s_at 3 M5005_Spy0463 - Hypothetical cytosolic protein Phage 3.104425586 22.62965037 acute PPA1&2 SpM18_ChORF0630_s_at 14 M5005_Spy0858 xpt Xanthine phosphoribosyltransferase (EC 2.4.2.-) Unknown 3.095197857 23.29035968 acute PPA1&2 SpM1_ChORF1136_s_at 7 M5005_Spy1203 - Phage protein Phage 3.082544316 24.22544696 acute PPA1&2 SpM3_ChORF1132_at 5 M5005_Spy0948 ciaR Transcriptional regulatory protein ciaR Signal transduction 3.067283838 25.39940742 acute PPA1&2 SpM1_ChORF1237_s_at 7 M5005_Spy1206 - Phage protein Phage 3.048762885 7.067149897 acute PPA3 SpM1_ChORF1479_s_at M5005_Spy1723 isp Immunogenic secreted protein Virulence 3.047876362 26.96844663 acute PPA1&2 SpM12_ChORF249-5_s_at 13 M5005_Spy1681 dexB Glucan 1,6-alpha-glucosidase (EC 3.2.1.70) Carbohydrate metabolism 3.046560583 27.07800267 acute PPA1&2 SpM18_ChORF2039_s_at 2 M5005_Spy1614 - Hypothetical protein Unknown 3.028249097 28.64600204 acute PPA1&2 SpM1_ChORF1898_s_at 4 M5005_Spy1548 comEB ComE operon protein 2 Membrane transport 3.027442209 28.71698766 acute PPA1&2 SpM1_ChORF1823_s_at 2 M5005_Spy0866 - Phosphinothricin N-acetyltransferase (EC 2.3.1.-) Unknown 3.009167619 7.997965938 acute PPA3 SpM1_ChORF1144_s_at M5005_Spy0065 adk Adenylate kinase (EC 2.7.4.3) Cellular processing 2.990386051 8.477852508 acute PPA3 SpM1_ChORF0074_s_at M5005_Spy0715 - SSU ribosomal protein S1P Protein synthesis 2.97549923 8.87688972 acute PPA3 SpM1_ChORF0913_s_at M5005_Spy0368 mtsA Manganese-binding protein Membrane transport 2.926714006 10.30863886 acute PPA3 SpM1_ChORF0453_s_at M5005_Spy1354 recU Recombination protein recU Unknown 2.886597237 11.64140304 acute PPA3 SpM1_ChORF1648_s_at M5005_Spy0189 - Hypothetical protein Unknown 2.88541677 11.68290749 acute PPA3 SpM1_ChORF0219_x_at M5005_Spy1638 lacA.2 Galactose-6-phosphate isomerase lacA subunit (EC 5.3.1.26) Carbohydrate metabolism 2.842842301 13.27337038 acute PPA3 SpM1_ChORF1923_s_at M5005_Spy0916 ylxM Signal recognition particle associated protein Secretion 2.823988679 14.03888777 acute PPA3 SpM1_ChORF1201_s_at M5005_Spy0838 - /Acylhydrolase family protein Unknown 2.785273681 15.73840722 acute PPA3 SpM1_ChORF1115_s_at M5005_Spy1825 - Transcriptional regulator, PadR family Phage 2.777872892 16.08384851 acute PPA3 SpM1_ChORF2172_s_at M5005_Spy0293 greA Transcription elongation factor greA Information processing 2.629567798 24.62738479 acute PPA3 SpM1_ChORF0349_s_at M5005_Spy0161 perR Ferric uptake regulation protein Information processing 2.614437703 25.69645058 acute PPA3 SpM1_ChORF0187_s_at M5005_Spy0988 pyk, pykA (EC 2.7.1.40) Carbohydrate metabolism 2.593108594 27.27445341 acute PPA3 SpM1_ChORF1282_s_at M5005_Spy1405 copA Copper-exporting ATPase (EC 3.6.3.4) Membrane transport 2.576570273 28.55735727 acute PPA3 SpM49_ChORF1257-5_at M5005_Spy0410 - ATPase Unknown 2.576459231 28.56615096 acute PPA3 SpM1_ChORF0500_s_at M5005_Spy1863 - Phage 2.523169298 33.07748612 acute PPA3 SpM18_ChORF1319_s_at

Page 3 of 8 Table 3. GAS genes with negative or positive Z-scores (± 2.0 or higher) to SEGS values.

M5005_gene Gene Description Function Z(SEGS ) NFD(SEGS ) Phase Analysis Probe-set Probe M5005_Spy0682 mvaK1 (EC 2.7.1.36) Lipid metabolism 2.509552434 34.32794695 acute PPA3 SpM1_ChORF0876_s_at M5005_Spy1240 clpE ATP-dependent clp protease ATP-binding subunit clpE Stress 2.503065817 34.93833343 acute PPA3 SpM1_ChORF1509_s_at M5005_Spy1074 - Hypothetical protein Unknown 2.454998522 39.77138646 acute PPA3 SpM3_ChORF0995_at M5005_Spy1085 bglA.2 Beta-glucosidase (EC 3.2.1.21) Carbohydrate metabolism 2.38941909 47.32082665 acute PPA3 SpM1_ChORF1328_s_at M5005_Spy1218 - Phage protein Phage 2.365788409 50.33688182 acute PPA3 SpyM3_1262_at M5005_Spy0123 - Translation initiation inhibitor Cellular processing 2.362569136 50.76062952 acute PPA3 SpM1_ChORF0145_s_at M5005_Spy1424 - Phage endopeptidase Phage 2.362192968 50.8103487 acute PPA3 SpM12_ChORF299-62_at M5005_Spy0626 - Hypothetical cytosolic protein Unknown 2.342197454 53.51580877 acute PPA3 SpM1_ChORF0811_s_at M5005_Spy0508 tufA Protein Translation Elongation Factor Tu (EF-TU) Cellular processing 2.288589351 61.40448166 acute PPA3 SpM1_ChORF0611_s_at M5005_Spy0360 - NAD-dependent Unknown 2.274506561 63.63884218 acute PPA3 SpM18_ChORF0484_at M5005_Spy0954 pstC Phosphate transport system permease protein pstC Membrane transport 2.270862681 64.22843772 acute PPA3 SpM1_ChORF1244_s_at M5005_Spy1627 salY ABC transporter permease protein Membrane transport 2.244959351 68.5591216 acute PPA3 SpM1_ChORF1911_s_at M5005_Spy1173 - Phage protein Phage 2.242699911 68.94868121 acute PPA3 SpM18_ChORF1247_at M5005_Spy1503 - Phosphoglycerate mutase (EC 5.4.2.1) Carbohydrate metabolism 2.238546885 69.669761 acute PPA3 SpM1_ChORF1766_s_at M5005_Spy0999 - Phage protein Phage 2.226656039 71.77082667 acute PPA3 SpM49_ChORF7585-42_at M5005_Spy1097 - , Pnp/Udp family Unknown 2.208288733 75.12471347 acute PPA3 SpM49_ChORF903-3_s_at M5005_Spy0224 rpe Ribulose-phosphate 3-epimerase (EC 5.1.3.1) Carbohydrate metabolism 2.207896918 75.19771943 acute PPA3 SpM1_ChORF0264_s_at M5005_Spy0021 acpP.2 Acyl carrier protein Cellular processing 2.205599239 75.6270827 acute PPA3 SpM1_ChORF0023_s_at M5005_Spy1321 - Hypothetical cytosolic protein Unknown 2.197440632 77.1689282 acute PPA3 SpM1_ChORF1608_s_at M5005_Spy1845 - Cobalt transport ATP-binding protein cbiO Membrane transport 2.182783291 80.00757853 acute PPA3 SpM1_ChORF2193_s_at M5005_Spy1424 - Phage endopeptidase Phage 2.163358611 83.90871516 acute PPA3 SpM5_ChORF270b-369_at M5005_Spy1726 - ABC transporter permease protein Membrane transport 2.142615948 88.25523617 acute PPA3 SpM1_ChORF2029_s_at M5005_Spy1348 - D-beta-hydroxybutyrate permease Unknown 2.141216893 88.55527625 acute PPA3 SpM1_ChORF1641_s_at M5005_Spy0148 - PTS system, 3-keto-L-gulonate specific IIC component (EC 2.7.1.69) Membrane transport 2.134886521 89.92391275 acute PPA3 SpM1_ChORF0174_s_at M5005_Spy0370 mtsC Manganese transport system membrane protein mntB Membrane transport 2.117993939 93.66576377 acute PPA3 SpM1_ChORF0456_s_at M5005_Spy0932 - Luciferase-like monooxygenase (EC 1.14.-.-) Unknown 2.114717132 94.40692734 acute PPA3 SpM1_ChORF1219_s_at M5005_Spy1508 gatC Glutamyl-tRNA(Gln) amidotransferase subunit C (EC 6.3.5.-) Protein synthesis 2.096997892 98.50279173 acute PPA3 SpM12_ChORF294-3_x_at M5005_Spy1672 polC DNA polymerase III alpha subunit (EC 2.7.7.7) Information processing 2.089281491 100.333635 acute PPA3 SpM1_ChORF1961_s_at M5005_Spy1700 - Acetyltransferase (EC 2.3.1.-) Cellular processing 2.082277608 102.0206316 acute PPA3 SpM1_ChORF1994_s_at M5005_Spy1138 - Ribosomal small subunit pseudouridine synthase A (EC 4.2.1.70) Protein synthesis 2.079347081 102.7336815 acute PPA3 SpM1_ChORF1398_s_at M5005_Spy0339 exoA III (EC 3.1.11.2) Information processing 2.070958987 104.7983158 acute PPA3 SpM1_ChORF0412_s_at M5005_Spy0695 rpiA Ribose 5-phosphate isomerase (EC 5.3.1.6) Carbohydrate metabolism 2.058857811 107.8394399 acute PPA3 SpM1_ChORF0889_s_at M5005_Spy1144 - Hypothetical protein Unknown 2.050838549 109.8960642 acute PPA3 SpM1_ChORF1405_s_at M5005_Spy1229 argR Arginine repressor, argR Information processing 2.026480826 116.3495102 acute PPA3 SpM1_ChORF1497_s_at M5005_Spy1569 pfl Formate acetyltransferase (EC 2.3.1.54) Carbohydrate metabolism 2.011011821 120.6133697 acute PPA3 SpM1_ChORF1849_s_at M5005_Spy1423 - Hyaluronoglucosaminidase (EC 3.2.1.35) Phage -5.216330076 0.007485969 asym. PPA1&2 SpM12_ChORF299-63_at 16 M5005_Spy0504 pepF Oligoendopeptidase F (EC 3.4.24.-) Amino acid metabolism -4.331206282 0.296785995 asym. PPA1&2 SpM1_ChORF0606_s_at 10 M5005_Spy1186 - Phage protein Phage -4.323906633 0.305389038 asym. PPA1&2 SpM1_ChORF1456_s_at 15 M5005_Spy0871 - Multidrug resistance ABC transporter ATP-binding and permease protein Membrane transport -4.320521915 0.309459061 asym. PPA1&2 SpM1_ChORF1149_s_at 9 M5005_Spy0783 ptsD PTS system, mannose/fructose family IID component Carbohydrate metabolism -4.206162395 0.48212507 asym. PPA1&2 SpM1_ChORF1060_s_at 13 M5005_Spy1466 - Phage protein Phage -4.196697521 0.499972759 asym. PPA1&2 SpM12_ChORF299-14_at 12 M5005_Spy0868 - Hypothetical protein Unknown -4.1030198 0.714393283 asym. PPA1&2 SpM1_ChORF1146_s_at 6 M5005_Spy0027 - IMP CYCLOHYDROLASE (EC 3.5.4.10) Nucleotide metabolism -4.042526536 0.897014541 asym. PPA1&2 SpM18_ChORF0030_s_at 1 M5005_Spy0767 - 4-nitrophenylphosphatase (EC 3.1.3.41) Unknown -3.892686026 1.561207204 asym. PPA1&2 SpM1_ChORF1043_s_at 12 M5005_Spy0680 - Two-component response regulator Signal transduction -3.858649146 1.767166565 asym. PPA1&2 SpM1_ChORF0874_s_at 11 M5005_Spy1818 cadC Cadmium efflux system accessory protein Membrane transport -3.854956463 1.791005758 asym. PPA1&2 SpM1_ChORF2163_s_at 6 M5005_Spy0135 - Hypothetical membrane associated protein Unknown -3.775054045 2.38833708 asym. PPA1&2 SpM1_ChORF0159_s_at 4 M5005_Spy0517 regR Transcriptional regulator, LacI family Information processing -3.718295416 2.922851942 asym. PPA1&2 SpM1_ChORF0627_s_at 12 M5005_Spy0537 aspC Aspartate aminotransferase (EC 2.6.1.1) Amino acid metabolism -3.713735557 2.97039385 asym. PPA1&2 SpM1_ChORF0650_s_at 12 M5005_Spy0850 pta putative phosphotransacetylase Cellular processing -3.712057722 2.988071055 asym. PPA1&2 SpM1_ChORF1128_s_at 2 M5005_Spy0539 - ATP-binding protein (contains P-loop) Membrane transport -3.706946834 3.042534595 asym. PPA1&2 SpM1_ChORF0652_s_at 12 M5005_Spy0061 rpsE SSU ribosomal protein S5P Protein synthesis -3.564877715 4.992516532 asym. PPA1&2 SpM1_ChORF0069_s_at 1 M5005_Spy0780 - PTS system, mannose/fructose family IIA component Unknown -3.558956355 5.095166371 asym. PPA1&2 SpM1_ChORF1057_s_at 4 M5005_Spy0868 - Hypothetical protein Unknown -3.498271411 6.268403115 asym. PPA1&2 SpM1_ChORF1146_s_at 13 M5005_Spy0681 - Two component system (EC 2.7.3.-) Signal transduction -3.470882902 6.877391164 asym. PPA1&2 SpM1_ChORF0875_s_at 10 M5005_Spy0058 rpsH SSU ribosomal protein S8P Protein synthesis -3.453323491 7.296659007 asym. PPA1&2 SpM1_ChORF0065_s_at 2 M5005_Spy0764 - Hypothetical protein Unknown -3.451868835 7.332449053 asym. PPA1&2 SpM1_ChORF1039_s_at 2 M5005_Spy1685 - D-tyrosyl-tRNA(Tyr) deacylase (EC 3.1.-.-) Protein synthesis -3.432458086 7.826096765 asym. PPA1&2 SpyM3_1699_at 15 M5005_Spy1412 nusA N utilization substance protein A Cellular processing -3.424128817 8.047355927 asym. PPA1&2 SpM1_ChORF1724_s_at 4 M5005_Spy0444 - Hypothetical protein Unknown -3.397247822 2.432665214 asym. PPA3 SpM12_ChORF277-20_s_at M5005_Spy1486 accC Biotin carboxylase (EC 6.3.4.14) Cell wall metabolism -3.390720473 2.486020397 asym. PPA3 SpM1_ChORF1745_s_at M5005_Spy1184 - Phage protein Phage -3.380925254 9.292393133 asym. PPA1&2 SpM1_ChORF1455_s_at 2 M5005_Spy1519 recG ATP-dependent DNA helicase recG (EC 3.6.1.-) Information processing -3.35546511 10.10845036 asym. PPA1&2 SpM1_ChORF1785_s_at 4 M5005_Spy1722 - Hypothetical protein Unknown -3.320307798 3.135741477 asym. PPA3 SpM1_ChORF2023_s_at M5005_Spy1120 pstI Phosphoenolpyruvate-protein (EC 2.7.3.9) Carbohydrate metabolism -3.314284921 3.198133647 asym. PPA3 SpM1_ChORF1372_s_at M5005_Spy0384 - Surface antigen Virulence -3.311211515 11.68868554 asym. PPA1&2 SpM1_ChORF0469_s_at 9

Page 4 of 8 Table 3. GAS genes with negative or positive Z-scores (± 2.0 or higher) to SEGS values.

M5005_gene Gene Description Function Z(SEGS ) NFD(SEGS ) Phase Analysis Probe-set Probe M5005_Spy0466 - Hypothetical phage protein Phage -3.303624186 11.98180002 asym. PPA1&2 SpM18_ChORF0632_s_at 13 M5005_Spy1083 - Transcription antiterminator, BglG family Information processing -3.287297784 12.63598108 asym. PPA1&2 SpM1_ChORF1325_s_at 12 M5005_Spy0834 - Zn-dependent alcohol dehydrogenases and related dehydrogenases Unknown -3.28182996 12.86242904 asym. PPA1&2 SpM1_ChORF1111_s_at 14 M5005_Spy0223 - GTPase (EC 3.6.1.-) Unknown -3.275939861 13.11060343 asym. PPA1&2 SpM1_ChORF0263_s_at 2 M5005_Spy1156 - Hypothetical Membrane Spanning Protein Unknown -3.265707239 3.745496945 asym. PPA3 SpM1_ChORF1419_s_at M5005_Spy1117 deaD2 ATP-dependent RNA helicase Stress -3.240898929 14.68188904 asym. PPA1&2 SpM1_ChORF1369_s_at 8 M5005_Spy0962 - Hypothetical protein Unknown -3.22528854 15.43697381 asym. PPA1&2 SpM1_ChORF1252_s_at 7 M5005_Spy1346 atoA Acetate CoA-transferase beta subunit (EC 2.8.3.8) Cell wall metabolism -3.208577476 4.500792758 asym. PPA3 SpM1_ChORF1639_s_at M5005_Spy0318 pflC Pyruvate formate-lyase activating enzyme (EC 1.97.1.4) Carbohydrate metabolism -3.193399082 17.09327816 asym. PPA1&2 SpM1_ChORF0379_s_at 1 M5005_Spy0066 infA Bacterial Protein Translation Initiation Factor 1 (IF-1) Cellular processing -3.167588232 18.55343013 asym. PPA1&2 SpM1_ChORF0075_s_at 3 M5005_Spy0058 rpsH SSU ribosomal protein S8P Protein synthesis -3.166716579 18.60470802 asym. PPA1&2 SpM1_ChORF0065_s_at 15 M5005_Spy0121 - Acetyl-CoA:acetoacetyl-CoA transferase beta subunit (EC 2.8.3.-) Carbohydrate metabolism -3.153036204 19.42695837 asym. PPA1&2 SpM1_ChORF0142_s_at 1 M5005_Spy0264 - Hydrolase (HAD superfamily) Unknown -3.1418665 20.12321039 asym. PPA1&2 SpM1_ChORF0309_s_at 9 M5005_Spy1077 glnQ.2 Glutamine transport ATP-binding protein glnQ Membrane transport -3.139799861 20.25454571 asym. PPA1&2 SpM1_ChORF1316_s_at 2 M5005_Spy1140 queA S-adenosylmethionine:tRNA ribosyltransferase-isomerase (EC 5.-.-.-) Protein synthesis -3.136894369 20.44053681 asym. PPA1&2 SpM1_ChORF1400_s_at 3 M5005_Spy0057 rpsN SSU ribosomal protein S14P Protein synthesis -3.113849697 21.97284948 asym. PPA1&2 SpM1_ChORF0064_s_at 5 M5005_Spy0073 - Hypothetical protein Unknown -3.108763717 6.1700119 asym. PPA3 SpM1_ChORF0084_s_at M5005_Spy1581 - Transcriptional regulator, MerR family Information processing -3.108428234 22.34849834 asym. PPA1&2 SpM1_ChORF1863_s_at 10 M5005_Spy0291 - Acetyltransferase (GNAT) family Unknown -3.093317946 23.42713531 asym. PPA1&2 SpM1_ChORF0346_s_at 10 M5005_Spy1268 - Methyltransferase (EC 2.1.1.-) Unknown -3.091602333 6.509264636 asym. PPA3 SpM1_ChORF1538_s_at M5005_Spy1162 - Hypothetical protein Unknown -3.065782387 25.51771239 asym. PPA1&2 SpM1_ChORF1425_s_at 14 M5005_Spy1163 - Transcriptional regulator, biotin repressor family Information processing -3.045289397 27.18423637 asym. PPA1&2 SpM1_ChORF1427_s_at 2 M5005_Spy1753 pbp2A Multimodular transpeptidase-transglycosylase PBP 2A Cell wall metabolism -3.016868338 29.66235776 asym. PPA1&2 SpM1_ChORF2059_s_at 10 M5005_Spy0038 - Acyltransferase family Unknown -3.00540974 30.71921048 asym. PPA1&2 SpM1_ChORF0041_s_at 9 M5005_Spy1064 malC Maltose transport system permease protein malF Membrane transport -3.002107449 31.03017584 asym. PPA1&2 SpM1_ChORF1301_at 10 M5005_Spy0554 - Septation ring formation regulator Cellular processing -3.001379097 8.59491333 asym. PPA3 SpM1_ChORF0728_s_at M5005_Spy1197 - Phage protein Phage -2.96404514 9.626043011 asym. PPA3 SpM3_ChORF1124_s_at M5005_Spy1098 - tRNA (Uracil-5-) -methyltransferase (EC 2.1.1.35) Protein synthesis -2.945154662 10.19011035 asym. PPA3 SpM1_ChORF1346_s_at M5005_Spy1498 dnaK Chaperone protein dnaK Stress -2.910886208 11.29160668 asym. PPA3 SpM1_ChORF1760_s_at M5005_Spy0263 nadD Nicotinate-nucleotide adenylyltransferase (EC 2.7.7.18) Coenzyme and cofactor metabolism -2.869527233 12.76620407 asym. PPA3 SpM5_ChORFJ7578C-5_s_at M5005_Spy0442 - Hypothetical cytosolic protein Unknown -2.848101228 13.59764238 asym. PPA3 SpM1_ChORF0535_s_at M5005_Spy1492 fabK Enoyl-[acyl-carrier protein] reductase (NADH) (EC 1.3.1.9) Lipid metabolism -2.846337255 13.66825481 asym. PPA3 SpM5_ChORF169a-220_at M5005_Spy0443 - Hypothetical protein Unknown -2.81760927 14.8664751 asym. PPA3 SpM1_ChORF0536_s_at M5005_Spy1415 sdaD2 Streptodornase (EC 3.1.21.1) Virulence -2.815532506 14.95670914 asym. PPA3 SpM12_ChORF251-8_at M5005_Spy1288 - Hypothetical cytosolic protein Unknown -2.720981163 19.63462586 asym. PPA3 SpM1_ChORF1564_s_at M5005_Spy1131 - Transcriptional regulator, Cro/CI family Information processing -2.717188021 19.84741701 asym. PPA3 SpM1_ChORF1385_s_at M5005_Spy1702 smeZ mitogenic exotoxin Z Virulence -2.710862043 20.20695965 asym. PPA3 SpM12_ChORF291-40_s_at M5005_Spy0634 - hypothetical ribosome-associated protein Unknown -2.673035536 22.48296461 asym. PPA3 SpM1_ChORF0821_s_at M5005_Spy0791 uvrC Excinuclease ABC subunit C Information processing -2.654774707 23.66271599 asym. PPA3 SpM1_ChORF1068_s_at M5005_Spy0334 - Hypothetical protein Unknown -2.633342532 25.11857016 asym. PPA3 SpM1_ChORF0405_s_at M5005_Spy0691 clpX ATP-dependent clp protease ATP-binding subunit clpX Stress -2.545589331 31.95982943 asym. PPA3 SpM1_ChORF0885_s_at M5005_Spy1728 - periplasmic component of efflux system Membrane transport -2.506923892 35.47293148 asym. PPA3 SpM1_ChORF2032_s_at M5005_Spy0276 - Potassium uptake protein ktrA Membrane transport -2.470950341 39.04765339 asym. PPA3 SpM1_ChORF0326_s_at M5005_Spy1174 - Phage protein Phage -2.410640198 45.76607015 asym. PPA3 SpM18_ChORF0774_s_at M5005_Spy1045 - Transcriptional regulator Phage -2.409235838 45.93405594 asym. PPA3 SpM18_ChORF1302_at M5005_Spy0441 aroE.2 Shikimate 5-dehydrogenase (EC 1.1.1.25) Amino acid metabolism -2.3980464 47.29218008 asym. PPA3 SpM1_ChORF0534_s_at M5005_Spy0739 - Tetratricopeptide repeat family protein Unknown -2.391642869 48.0853339 asym. PPA3 SpM1_ChORF1012_s_at M5005_Spy0598 mscL Large-conductance mechanosensitive channel Membrane transport -2.387495188 48.60534544 asym. PPA3 SpM1_ChORF0780_s_at M5005_Spy0646 - ABC transporter permease protein Membrane transport -2.371586142 50.64643627 asym. PPA3 SpM1_ChORF0838_s_at M5005_Spy1428 - Phage protein Phage -2.36548934 51.44852442 asym. PPA3 SpM12_ChORF299-58_s_at M5005_Spy1556 - Hypothetical protein Unknown -2.354039975 52.98519908 asym. PPA3 SpM1_ChORF1832_s_at M5005_Spy0389 dgk (EC 2.7.1.107) Lipid metabolism -2.307857268 59.60297837 asym. PPA3 SpM1_ChORF0475_s_at M5005_Spy0867 glyA Serine hydroxymethyltransferase (EC 2.1.2.1) Cellular processing -2.285989288 62.98286048 asym. PPA3 SpM1_ChORF1145_s_at M5005_Spy1303 aroE Shikimate 5-dehydrogenase (EC 1.1.1.25) Amino acid metabolism -2.26380555 66.58237863 asym. PPA3 SpM18_ChORF1591_s_at M5005_Spy0195 - Transcriptional regulator, MarR family Cellular processing -2.256674998 67.77705416 asym. PPA3 SpM1_ChORF0227_s_at M5005_Spy1435 - Phage scaffold protein Phage -2.222479442 73.7707861 asym. PPA3 SpM12_ChORF299-7_at M5005_Spy0010 - predicted open reading frame Unknown -2.215158524 75.11251327 asym. PPA3 SpM12_ChORF239-12_s_at M5005_Spy1064 malC Maltose transport system permease protein malF Membrane transport -2.197895333 78.36094358 asym. PPA3 SpM1_ChORF1301_at M5005_Spy1254 - Hypothetical membrane spanning protein Unknown -2.19171455 79.55336941 asym. PPA3 SpM1_ChORF1526_s_at M5005_Spy1049 - Phage protein Phage -2.185027138 80.86128759 asym. PPA3 SpM3_ChORF0976_s_at M5005_Spy0519 agaD PTS system, N-acetylgalactosamine-specific IID component (EC 2.7.1.69) Carbohydrate metabolism -2.184727107 80.92040322 asym. PPA3 SpM1_ChORF0630_s_at M5005_Spy1000 - Phage protein Phage -2.177793741 82.29699823 asym. PPA3 SpM49_ChORF7585-41_at M5005_Spy0008 divIC Cell division protein DIVIC Cellular processing -2.166754608 84.53076739 asym. PPA3 SpM1_ChORF0009_s_at M5005_Spy1578 - Transcriptional regulator, Cro/CI family Information processing -2.147748206 88.50009893 asym. PPA3 SpM18_ChORF1923_at M5005_Spy1805 mutS DNA mismatch repair protein mutS Information processing -2.146373043 88.79345284 asym. PPA3 SpM1_ChORF2148_s_at M5005_Spy1771 hutU Urocanate hydratase (EC 4.2.1.49) Amino acid metabolism -2.146012242 88.87055925 asym. PPA3 SpM12_ChORF298-11_at

Page 5 of 8 Table 3. GAS genes with negative or positive Z-scores (± 2.0 or higher) to SEGS values.

M5005_gene Gene Description Function Z(SEGS ) NFD(SEGS ) Phase Analysis Probe-set Probe M5005_Spy1649 - Hypothetical membrane spanning protein Unknown -2.13875554 90.43373706 asym. PPA3 SpM1_ChORF1934_s_at M5005_Spy1050 - Phage transcriptional repressor Phage -2.136278899 90.97265195 asym. PPA3 SpM12_ChORF276-12_at M5005_Spy0160 - CoA binding protein Unknown -2.129355237 92.4939956 asym. PPA3 SpM1_ChORF0186_s_at M5005_Spy1083 - Transcription antiterminator, BglG family Information processing -2.113381919 96.08793563 asym. PPA3 SpM1_ChORF1325_s_at M5005_Spy0786 - Iron(III)-binding protein Membrane transport -2.112018657 96.40017159 asym. PPA3 SpM1_ChORF1063_at M5005_Spy0702 - Hypothetical protein Unknown -2.093604545 100.7041669 asym. PPA3 SpM1_ChORF0899_s_at M5005_Spy0871 - Multidrug resistance ABC transporter ATP-binding and permease protein Membrane transport -2.081442938 103.6365853 asym. PPA3 SpM1_ChORF1149_s_at M5005_Spy0071 rplQ LSU ribosomal protein L17P Protein synthesis -2.080394875 103.8926966 asym. PPA3 SpM1_ChORF0080a_s_at M5005_Spy0632 capA Capsule biosynthesis protein capA Unknown -2.080033779 103.9810623 asym. PPA3 SpM1_ChORF0818_s_at M5005_Spy0116 atoE Short-chain fatty acids transporter Membrane transport -2.077629522 104.5710686 asym. PPA3 SpM1_ChORF0137_s_at M5005_Spy1633 lacE PTS system, lactose-specific IIBC component (EC 2.7.1.69) Carbohydrate metabolism -2.073659532 105.5516038 asym. PPA3 SpM1_ChORF1917_s_at M5005_Spy1744 - PTS system, cellobiose-specific IIC component Carbohydrate metabolism -2.073071044 105.6976224 asym. PPA3 SpM1_ChORF2050_s_at M5005_Spy1623 hsdM Type I restriction-modification system methylation subunit Information processing -2.07242366 105.8584551 asym. PPA3 SpM1_ChORF1906_s_at M5005_Spy1652 - 23S rRNA methyltransferase (EC 2.1.1.-) Cellular processing -2.068464459 106.8466374 asym. PPA3 SpM1_ChORF1938_s_at M5005_Spy1662 - Putative transport protein sgaT Membrane transport -2.065650306 107.5538302 asym. PPA3 SpM1_ChORF1949_s_at M5005_Spy0391 - Phosphohydrolase (MutT/nudix family protein) Unknown -2.063811454 108.0180979 asym. PPA3 SpM1_ChORF0477_s_at M5005_Spy0929 - SIR2 family protein Information processing -2.052170013 110.9973642 asym. PPA3 SpM1_ChORF1215_s_at M5005_Spy0209 - Jag protein Cellular processing -2.047078257 112.3224076 asym. PPA3 SpM1_ChORF0248_s_at M5005_Spy0658 - regulatory protein (pfoS/R) Information processing -2.034962775 115.529808 asym. PPA3 SpM1_ChORF0851_s_at M5005_Spy1009 - Phage protein Phage -2.028108533 117.3788133 asym. PPA3 SpM49_ChORF7585-30_at M5005_Spy1582 dnaQ DNA polymerase III, epsilon chain (EC 2.7.7.7) Cellular processing -2.003114566 124.3368148 asym. PPA3 SpM1_ChORF1864_s_at M5005_Spy1546 nusB General stress protein, Gls24 family Stress 5.72326602 0.000211619 asym. PPA3 SpM1_ChORF1820_s_at M5005_Spy0373 - Integral membrane protein Unknown 4.855757116 0.035220672 asym. PPA1&2 SpM1_ChORF0459_s_at 4 M5005_Spy1442 - Phage transcriptional activator Phage 4.787877581 0.046797121 asym. PPA1&2 SpM12_ChORF299-47_s_at 1 M5005_Spy1239 - Hypothetical cytosolic protein Unknown 4.657600573 0.022163109 asym. PPA3 SpM1_ChORF1508_s_at M5005_Spy0950 phoU Phosphate transport system protein phoU Membrane transport 4.300429414 0.092505715 asym. PPA3 SpM1_ChORF1240_s_at M5005_Spy0068 rpsM SSU ribosomal protein S13P Protein synthesis 4.175764904 0.149716913 asym. PPA3 SpM1_ChORF0077_s_at M5005_Spy1731 - Hypothetical cytosolic protein Unknown 4.041504665 0.248859435 asym. PPA3 SpM18_ChORF2095_s_at M5005_Spy0506 ftsW Cell division protein ftsW Cellular processing 4.032964464 0.929688747 asym. PPA1&2 SpM1_ChORF0609_s_at 3 M5005_Spy0148 - PTS system, 3-keto-L-gulonate specific IIC component (EC 2.7.1.69) Membrane transport 4.010797623 0.279098271 asym. PPA3 SpM1_ChORF0174_s_at M5005_Spy0245 nifU, yurV IscU protein Coenzyme and cofactor metabolism 3.96883563 1.180083659 asym. PPA1&2 SpM1_ChORF0289_s_at 2 M5005_Spy1792 - Hypothetical protein Unknown 3.922936612 1.397539785 asym. PPA1&2 SpM18_ChORF2167_x_at 14 M5005_Spy1215 - Phage protein Phage 3.876472084 1.656290999 asym. PPA1&2 SpM1_ChORF0948_s_at 5 M5005_Spy0932 - Luciferase-like monooxygenase (EC 1.14.-.-) Unknown 3.852674993 1.805887095 asym. PPA1&2 SpM1_ChORF1219_s_at 16 M5005_Spy0114 - Sortase Cell wall metabolism 3.837522693 1.907748107 asym. PPA1&2 SpM12_ChORF300-50_s_at 11 M5005_Spy0913 - Integrase/recombinase xerD Phage 3.824863765 1.997015582 asym. PPA1&2 SpM1_ChORF1196_s_at 15 M5005_Spy0218 - N-acetylmannosamine kinase (EC 2.7.1.60) / Transcriptional regulator Carbohydrate metabolism 3.760220444 2.518289808 asym. PPA1&2 SpM1_ChORF0258_s_at 13 M5005_Spy0134 - Tellurite resistance protein Unknown 3.679076719 3.356470665 asym. PPA1&2 SpM1_ChORF0158_s_at 9 M5005_Spy0445 metK S-adenosylmethionine synthetase (EC 2.5.1.6) Cellular processing 3.656932869 3.62752722 asym. PPA1&2 SpM1_ChORF0538_s_at 5 M5005_Spy0693 - Hypothetical protein Unknown 3.641313256 3.831045618 asym. PPA1&2 SpM1_ChORF0887_s_at 11 M5005_Spy0677 fms Peptide deformylase (EC 3.5.1.88) Information processing 3.585355298 4.652371784 asym. PPA1&2 SpM1_ChORF0870_s_at 6 M5005_Spy0128 ntpE V-type sodium ATP synthase subunit E (EC 3.6.3.14) Membrane transport 3.525461656 5.714324726 asym. PPA1&2 SpM1_ChORF0150_s_at 3 M5005_Spy1248 - Pyridoxal-5'-phosphate family protein Unknown 3.493810089 6.364011408 asym. PPA1&2 SpM1_ChORF1519_s_at 2 M5005_Spy1176 - Phage infection protein Phage 3.482365088 1.828362075 asym. PPA3 SpM1_ChORF1444_s_at M5005_Spy0581 atpD ATPase, beta subunit Carbohydrate metabolism 3.454535045 7.266975627 asym. PPA1&2 SpM12_ChORF269-12_s_at 13 M5005_Spy0747 - Zn-dependent hydrolase (EC 3.-.-.-) Unknown 3.423578455 8.062180791 asym. PPA1&2 SpM1_ChORF1020_s_at 5 M5005_Spy0521 agaV PTS system, N-acetylgalactosamine-specific IIB component (EC 2.7.1.69) Carbohydrate metabolism 3.412985769 8.352557372 asym. PPA1&2 SpM1_ChORF0631_s_at 9 M5005_Spy0308 - Hypothetical cytosolic protein Unknown 3.412630016 2.311148982 asym. PPA3 SpM1_ChORF0366_s_at M5005_Spy0212 - N-acetylmannosamine-6-phosphate 2-epimerase (EC 5.1.3.9) Carbohydrate metabolism 3.412363414 8.369919751 asym. PPA1&2 SpM1_ChORF0251_s_at 9 M5005_Spy0720 - putative exfoliative toxin Virulence 3.411902921 8.382788324 asym. PPA1&2 SpM12_ChORF248-9_s_at 13 M5005_Spy1215 - Phage protein Phage 3.409735415 8.443609572 asym. PPA1&2 SpM1_ChORF0948_s_at 3 M5005_Spy0224 rpe Ribulose-phosphate 3-epimerase (EC 5.1.3.1) Carbohydrate metabolism 3.397789778 8.786309554 asym. PPA1&2 SpM1_ChORF0264_s_at 2 M5005_Spy0602 rmlD dTDP-4-dehydrorhamnose reductase (EC 1.1.1.133) Cell wall metabolism 3.392115357 8.953632318 asym. PPA1&2 SpM1_ChORF0784_s_at 11 M5005_Spy1049 - Phage protein Phage 3.366370889 9.750999338 asym. PPA1&2 SpM18_ChORF1305_s_at 16 M5005_Spy1339 priA Primosomal protein N' Information processing 3.341979703 10.56742932 asym. PPA1&2 SpM1_ChORF1629_s_at 11 M5005_Spy1025 - Phage encoded transcriptional regulator, ArpU family Phage 3.286908109 12.65199522 asym. PPA1&2 SpM1_ChORF0677_s_at 13 M5005_Spy0918 - Hypothetical protein Unknown 3.282402931 3.548199401 asym. PPA3 SpM1_ChORF1203_s_at M5005_Spy0762 - Hypothetical membrane associated protein Unknown 3.273711341 13.20566087 asym. PPA1&2 SpM1_ChORF1037_s_at 1 M5005_Spy0094 ackA Acetate kinase (EC 2.7.2.1) Carbohydrate metabolism 3.234297265 14.99691268 asym. PPA1&2 SpM1_ChORF0109_s_at 14 M5005_Spy1146 - DNA polymerase III, delta subunit (EC 2.7.7.7) Information processing 3.231214322 15.1461757 asym. PPA1&2 SpM12_ChORF213-4_s_at 6 M5005_Spy0928 lplA Lipoate-protein ligase A (EC 6.-.-.-) Coenzyme and cofactor metabolism 3.203478912 16.55266137 asym. PPA1&2 SpM1_ChORF1214_s_at 10 M5005_Spy1304 lacZ Beta-galactosidase (EC 3.2.1.23) Carbohydrate metabolism 3.196845378 16.90661889 asym. PPA1&2 SpM1_ChORF1586_s_at 2 M5005_Spy0685 - Isopentenyl-diphosphate delta-isomerase (EC 5.3.3.2) Lipid metabolism 3.194230129 17.04809207 asym. PPA1&2 SpM1_ChORF0879_s_at 16 M5005_Spy1726 - ABC transporter permease protein Membrane transport 3.184109473 17.60602146 asym. PPA1&2 SpM1_ChORF2029_s_at 8 M5005_Spy1411 - Hypothetical cytosolic protein Unknown 3.16239352 18.86097917 asym. PPA1&2 SpM1_ChORF1722_s_at 9 M5005_Spy0550 - Chloride channel protein Membrane transport 3.156694712 5.307384748 asym. PPA3 SpM1_ChORF0723_at

Page 6 of 8 Table 3. GAS genes with negative or positive Z-scores (± 2.0 or higher) to SEGS values.

M5005_gene Gene Description Function Z(SEGS ) NFD(SEGS ) Phase Analysis Probe-set Probe M5005_Spy0065 adk Adenylate kinase (EC 2.7.4.3) Cellular processing 3.155811183 19.25748836 asym. PPA1&2 SpM1_ChORF0074_s_at 13 M5005_Spy0049 rplV LSU ribosomal protein L22P Protein synthesis 3.146057893 19.85927157 asym. PPA1&2 SpM1_ChORF0055_s_at 7 M5005_Spy0677 fms Peptide deformylase (EC 3.5.1.88) Information processing 3.145902057 19.86902694 asym. PPA1&2 SpM1_ChORF0870_s_at 16 M5005_Spy1108 metK S-adenosylmethionine synthetase (EC 2.5.1.6) Cellular processing 3.136995164 20.43405804 asym. PPA1&2 SpM1_ChORF1359_s_at 3 M5005_Spy0463 - Hypothetical cytosolic protein Phage 3.104425586 22.62965037 asym. PPA1&2 SpM18_ChORF0630_s_at 14 M5005_Spy0858 xpt Xanthine phosphoribosyltransferase (EC 2.4.2.-) Unknown 3.095197857 23.29035968 asym. PPA1&2 SpM1_ChORF1136_s_at 7 M5005_Spy1203 - Phage protein Phage 3.082544316 24.22544696 asym. PPA1&2 SpM3_ChORF1132_at 5 M5005_Spy1107 murZ UDP-N-acetylglucosamine 1-carboxyvinyltransferase (EC 2.5.1.7) Unknown 3.067742011 7.009718111 asym. PPA3 SpM1_ChORF1358_s_at M5005_Spy0948 ciaR Transcriptional regulatory protein ciaR Signal transduction 3.067283838 25.39940742 asym. PPA1&2 SpM1_ChORF1237_s_at 7 M5005_Spy0724 - Cystathionine beta-lyase (EC 4.4.1.8) / Cystathionine gamma-lyase (EC 4.4.1.1) Amino acid metabolism 3.056482327 7.258044866 asym. PPA3 SpM1_ChORF0923_s_at M5005_Spy0803 srtI protein involved in lantibiotic (srt) production Virulence 3.055484586 7.280437552 asym. PPA3 SpM12_ChORF284-43_s_at M5005_Spy1723 isp Immunogenic secreted protein Virulence 3.047876362 26.96844663 asym. PPA1&2 SpM12_ChORF249-5_s_at 13 M5005_Spy1681 dexB Glucan 1,6-alpha-glucosidase (EC 3.2.1.70) Carbohydrate metabolism 3.046560583 27.07800267 asym. PPA1&2 SpM18_ChORF2039_s_at 2 M5005_Spy1614 - Hypothetical protein Unknown 3.028249097 28.64600204 asym. PPA1&2 SpM1_ChORF1898_s_at 4 M5005_Spy1548 comEB ComE operon protein 2 Membrane transport 3.027442209 28.71698766 asym. PPA1&2 SpM1_ChORF1823_s_at 2 M5005_Spy1651 - Hypothetical cytosolic protein Unknown 3.017290597 8.187240437 asym. PPA3 SpM1_ChORF1937_s_at M5005_Spy1756 - Ribosomal large subunit pseudouridine synthase D (EC 4.2.1.70) Protein synthesis 2.998999501 8.657466888 asym. PPA3 SpM1_ChORF2063_s_at M5005_Spy0800 - DNA-cytosine methyltransferase (EC 2.1.1.73) Cellular processing 2.978193626 9.222558927 asym. PPA3 SpM1_ChORF1077_s_at M5005_Spy1040 - Phage protein Phage 2.956196719 9.85681117 asym. PPA3 SpM5_ChORF270b-7_at M5005_Spy1138 - Ribosomal small subunit pseudouridine synthase A (EC 4.2.1.70) Protein synthesis 2.92017083 10.98284279 asym. PPA3 SpM1_ChORF1398_s_at M5005_Spy0114 - Sortase Cell wall metabolism 2.888102 12.08338123 asym. PPA3 SpM1_ChORF0135_s_at M5005_Spy1106 grab Protein G-related alpha 2M-binding protein Virulence 2.860057291 13.1277692 asym. PPA3 SpM5_ChORF270b-528_at M5005_Spy0569 sagH Streptolysin S export transmembrane protein SagH Membrane transport 2.855399684 13.30901661 asym. PPA3 SpM1_ChORF0745_s_at M5005_Spy1054 - Phage protein Phage 2.83458047 14.14751733 asym. PPA3 SpM1_ChORF1290_s_at M5005_Spy1496 phaB Enoyl-CoA hydratase (EC 4.2.1.17) Cell wall metabolism 2.791822088 16.02295825 asym. PPA3 SpM1_ChORF1758_s_at M5005_Spy0582 atpC ATP synthase epsilon chain (EC 3.6.3.14) Carbohydrate metabolism 2.759435508 17.59146379 asym. PPA3 SpM1_ChORF0761_s_at M5005_Spy1681 dexB Glucan 1,6-alpha-glucosidase (EC 3.2.1.70) Carbohydrate metabolism 2.746440302 18.25920457 asym. PPA3 SpM1_ChORF1973_at M5005_Spy0778 csrA Peptide methionine sulfoxide reductase msrB (EC 1.8.4.6) Unknown 2.746115245 18.27619884 asym. PPA3 SpM1_ChORF1055_s_at M5005_Spy1405 copA Copper-exporting ATPase (EC 3.6.3.4) Membrane transport 2.729998986 19.1370293 asym. PPA3 SpM49_ChORF1257-5_at M5005_Spy0477 - Hypothetical membrane spanning protein Unknown 2.664677478 23.01617071 asym. PPA3 SpM1_ChORF0575_s_at M5005_Spy1585 deoC Deoxyribose-phosphate aldolase (EC 4.1.2.4) Carbohydrate metabolism 2.662809306 23.13690525 asym. PPA3 SpM1_ChORF1867_s_at M5005_Spy0687 mvaS.1 Hydroxymethylglutaryl-CoA synthase (EC 4.1.3.5) Lipid metabolism 2.657429161 23.4878164 asym. PPA3 SpM1_ChORF0880_s_at M5005_Spy0714 - Hypothetical cytosolic protein Unknown 2.637054699 24.86075604 asym. PPA3 SpM1_ChORF0912_s_at M5005_Spy0889 - regulatory protein (pfoS/R) Unknown 2.617137919 26.27249805 asym. PPA3 SpM1_ChORF1169_s_at M5005_Spy1034 - Phage protein Phage 2.61031705 26.77234939 asym. PPA3 SpM18_ChORF1794_s_at M5005_Spy0055 rplX LSU ribosomal protein L24P Protein synthesis 2.588737422 28.41072751 asym. PPA3 SpM1_ChORF0062_s_at M5005_Spy1146 - DNA polymerase III, delta subunit (EC 2.7.7.7) Information processing 2.576690491 29.36411393 asym. PPA3 SpM12_ChORF213-4_s_at M5005_Spy1375 tkt Transketolase (EC 2.2.1.1) Carbohydrate metabolism 2.557186376 30.96877911 asym. PPA3 SpM1_ChORF1676_s_at M5005_Spy0413 secG Protein translocase subunit secG Secretion 2.529494492 33.38239964 asym. PPA3 SpM1_ChORF0502_s_at M5005_Spy0361 - Phosphoglycerate transporter protein Membrane transport 2.508552797 35.31822691 asym. PPA3 SpM1_ChORF0442_s_at M5005_Spy0639 pyrR PyrR bifunctional protein Membrane transport 2.48718204 37.39668785 asym. PPA3 SpM5_ChORF4P31a-118_s_at M5005_Spy1424 - Phage endopeptidase Phage 2.428368312 43.69191313 asym. PPA3 SpM12_ChORF299-2_x_at M5005_Spy1370 - Gamma-glutamyl phosphate reductase (EC 1.2.1.41) Unknown 2.422022308 44.42457773 asym. PPA3 SpM18_ChORF1678_at M5005_Spy1702 smeZ mitogenic exotoxin Z Virulence 2.409644503 45.88511616 asym. PPA3 SpM1_ChORF1998_at M5005_Spy1354 recU Recombination protein recU Unknown 2.388085142 48.53107781 asym. PPA3 SpM1_ChORF1648_s_at M5005_Spy0523 - Hypothetical protein Membrane transport 2.383392408 49.1246243 asym. PPA3 SpM1_ChORF0634_s_at M5005_Spy1426 - Phage protein Phage 2.375542893 50.13183079 asym. PPA3 SpM12_ChORF299-4_at M5005_Spy0680 - Two-component response regulator Signal transduction 2.361930075 51.92195375 asym. PPA3 SpM1_ChORF0874_s_at M5005_Spy1102 - BN (EC 3.1.-.-) Cellular processing 2.34885347 53.69455367 asym. PPA3 SpM1_ChORF1353_s_at M5005_Spy0891 satD Hypothetical protein Unknown 2.341968192 54.64920014 asym. PPA3 SpM1_ChORF1171_s_at M5005_Spy1132 alaS Alanyl-tRNA synthetase (EC 6.1.1.7) Protein synthesis 2.327732921 56.67055244 asym. PPA3 SpM1_ChORF1389_s_at M5005_Spy0367 scaR Iron-dependent repressor Information processing 2.320161654 57.77226549 asym. PPA3 SpM1_ChORF0450_s_at M5005_Spy1316 - Hypothetical protein Unknown 2.30693912 59.74161023 asym. PPA3 SpM1_ChORF1603_s_at M5005_Spy1864 - Hypothetical cytosolic protein Unknown 2.29724722 61.22238966 asym. PPA3 SpM1_ChORF2215_s_at M5005_Spy0673 papS POLY(A) POLYMERASE (EC 2.7.7.19) Protein synthesis 2.291406547 62.13025663 asym. PPA3 SpM1_ChORF0866_s_at M5005_Spy0488 - Hypothetical protein Unknown 2.287900041 62.68096787 asym. PPA3 SpM1_ChORF0589_s_at M5005_Spy1743 pflD Formate acetyltransferase (EC 2.3.1.54) Carbohydrate metabolism 2.282296097 63.56999322 asym. PPA3 SpM1_ChORF2049_s_at M5005_Spy1723 isp Immunogenic secreted protein Virulence 2.280985499 63.77950045 asym. PPA3 SpM12_ChORF249-5_s_at M5005_Spy1818 cadC Cadmium efflux system accessory protein Membrane transport 2.272896806 65.08599017 asym. PPA3 SpM1_ChORF2163_s_at M5005_Spy0178 - Metal-dependent hydrolase (EC 3.-.-.-) Unknown 2.270972574 65.40022802 asym. PPA3 SpM1_ChORF0208_s_at M5005_Spy1657 - Hypothetical cytosolic protein Unknown 2.25917161 67.35664499 asym. PPA3 SpM18_ChORF2010_at M5005_Spy1002 - N-acetylmuramoyl-L-alanine amidase (EC 3.5.1.28) Phage 2.242120879 70.27388439 asym. PPA3 SpM49_ChORF7585-40_at M5005_Spy0715 - SSU ribosomal protein S1P Protein synthesis 2.234539472 71.60609815 asym. PPA3 SpM1_ChORF0913_s_at M5005_Spy0618 cmk (EC 2.7.4.14) Nucleotide metabolism 2.231429434 72.15894928 asym. PPA3 SpM1_ChORF0803_s_at M5005_Spy0803 srtI protein involved in lantibiotic (srt) production Virulence 2.223662509 73.55593653 asym. PPA3 SpM1_ChORF1080_s_at M5005_Spy1818 cadC Cadmium efflux system accessory protein Membrane transport 2.2084392 76.36266557 asym. PPA3 SpM18_ChORF2199_s_at

Page 7 of 8 Table 3. GAS genes with negative or positive Z-scores (± 2.0 or higher) to SEGS values.

M5005_gene Gene Description Function Z(SEGS ) NFD(SEGS ) Phase Analysis Probe-set Probe M5005_Spy0423 pepQ Xaa-Pro dipeptidase (EC 3.4.13.9) Amino acid metabolism 2.194899479 78.93696059 asym. PPA3 SpM1_ChORF0513_s_at M5005_Spy1262 - Transcriptional regulator Unknown 2.190371096 79.81463353 asym. PPA3 SpM1_ChORF1534_s_at M5005_Spy0977 pcrA DNA helicase II (EC 3.6.1.-) Cellular processing 2.170809011 83.70431852 asym. PPA3 SpM1_ChORF1267_s_at M5005_Spy0147 leuS Leucyl-tRNA synthetase (EC 6.1.1.4) Protein synthesis 2.157134349 86.52014469 asym. PPA3 SpM18_ChORF0171_at M5005_Spy1678 - Thioredoxin Stress 2.150804857 87.85104955 asym. PPA3 SpM1_ChORF1971_s_at M5005_Spy0974 - Small integral membrane protein Unknown 2.138778674 90.42871625 asym. PPA3 SpM18_ChORF1214_s_at M5005_Spy1259 dpr Ferroxidase (EC 1.16.3.1) Stress 2.12846889 92.69033228 asym. PPA3 SpM1_ChORF1531_s_at M5005_Spy0285 dnaB Replicative DNA helicase (EC 3.6.1.-) Unknown 2.126930984 93.03185227 asym. PPA3 SpM1_ChORF0339_s_at M5005_Spy1044 - Phage protein Phage 2.099099592 99.40279871 asym. PPA3 SpM3_ChORF0964_at M5005_Spy1373 - ABC transporter ATP-binding protein Membrane transport 2.098577745 99.52575994 asym. PPA3 SpM1_ChORF1674_s_at M5005_Spy0522 - Unsaturated glucuronyl hydrolase (EC 3.2.1.-) Unknown 2.09729015 99.82971246 asym. PPA3 SpM5_ChORFJ7578C-260_s_at M5005_Spy1799 recA RecA protein Information processing 2.091678736 101.1637055 asym. PPA3 SpM1_ChORF2116_s_at M5005_Spy0120 atoD.2 Acetate CoA-transferase alpha subunit (EC 2.8.3.8) Carbohydrate metabolism 2.085822498 102.572232 asym. PPA3 SpM1_ChORF0141_s_at M5005_Spy1425 - Phage protein Phage 2.083756647 103.0731133 asym. PPA3 SpM12_ChORF299-61_s_at M5005_Spy1531 isp2 Immunogenic secreted protein Virulence 2.077699592 104.553833 asym. PPA3 SpM1_ChORF1801_s_at M5005_Spy0277 ntpJ Potassium uptake protein ktrB Membrane transport 2.075364908 105.1294352 asym. PPA3 SpM1_ChORF0327_s_at M5005_Spy0163 - 3'-phosphoadenosine 5'-phosphosulfate sulfotransferase (PAPS reductase) Unknown 2.069056186 106.6984461 asym. PPA3 SpM1_ChORF0189_s_at M5005_Spy1424 - Phage endopeptidase Phage 2.06208738 108.454947 asym. PPA3 SpM12_ChORF299-62_at M5005_Spy1825 - Transcriptional regulator, PadR family Phage 2.058328321 109.4126807 asym. PPA3 SpM1_ChORF2172_s_at M5005_Spy0164 - ParB-like Unknown 2.058082421 109.475583 asym. PPA3 SpM1_ChORF0190_s_at M5005_Spy1630 salB Serine (threonine) dehydratase (lantibiotic biosynthesis) Virulence 2.053427558 110.6721788 asym. PPA3 SpM12_ChORF257-11_at M5005_Spy0509 tpi Triosephosphate isomerase (EC 5.3.1.1) Carbohydrate metabolism 2.048878496 111.8523863 asym. PPA3 SpM1_ChORF0613_s_at M5005_Spy0386 phoH PhoH protein Unknown 2.030071978 116.8465871 asym. PPA3 SpM1_ChORF0471_s_at M5005_Spy0670 rpsU Nucleoside diphosphate kinase (EC 2.7.4.6) Cellular processing 2.01581426 120.7586834 asym. PPA3 SpM18_ChORF0924_x_at

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