US 201701920 12A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2017/0192012 A1 Martin et al. (43) Pub. Date: Jul. 6, 2017

(54) COMPOSITIONS AND METHODS FOR (60) Provisional application No. 61/820,401, filed on May DETECTING S-NITROSYLATION AND 7, 2013. S-SULFNYLATION (71) Applicant: The Regents of the University of Publication Classification Michigan, Ann Arbor, MI (US) (51) Int. C. GOIN 33/68 (2006.01) (72) Inventors: Brent R. Martin, Ann Arbor, MI (US); (52) U.S. C. Jaimeen D. Majmudar, Ann Arbor, MI CPC ..... G0IN 33/6848 (2013.01); G0IN 2500/02 (US) (2013.01); G0IN 2440/26 (2013.01); G0IN (21) Appl. No.: 15/436,247 2440/30 (2013.01); G0IN 257.0/00 (2013.01) (22) Filed: Feb. 17, 2017 ABSTRACT Related U.S. Application Data (57) (63) Continuation of application No. 14/888,904, filed on The present invention relates to methods for detecting Nov. 3, 2015, filed as application No. PCT/US2014/ S-sulfinylation and S-sulfinylation within thiol 037111 on May 7, 2014. groups in , metabolites, or materials. Patent Application Publication Jul. 6, 2017. Sheet 1 of 141 US 2017/0192012 A1

FG. A

F.G. C FG D F.G. E.

K. . K.. . -X-Biotit-SQ. YaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaBiotin-SQ.

R3 : E3i:8888 88 i i ; : 2 283 kissee :3&tee 8w

See Patent Application Publication Jul. 6, 2017. Sheet 2 of 141 US 2017/0192012 A1

FG 2 Reacter; Progress. Phery:s:::::ic Acid anchi-ke-8-stroso-Cys-Okie

:

Resententine initities:

FG, 3 Penysulfiric Acid aid iodoacetatice

32 8. *s--c:r . !--- Bitter,i: , ;pri 3. kic *8388x3s ^e * 5 hours

8 :::::::s::::::::::::::::283 is:

8.

3. Ketetion inns irates

Patent Application Publication Jul. 6, 2017. Sheet 5 of 141 US 2017/0192012 A1

o-3-3-t --S s. (3 s'-ox 8 s sis." --- ... (88 k-, s s s -Xx & : 3- ---. i - '-- y Y-ch- is: 2 N- s &H 3 37 s 28 FIG. B. FG 7C ym Standard Curve (19) 7 : hiosulfonate Product, 3 34-Nie-Piloty's Acid, 28

y: 388x828: SO &s (3820: 1. s: S 40 3. 53 so 3. 33 Xtra 9:388) s so o Star&ard Curve (28 3. 2O 334:XX8. 3 y - 5333.8x + 3,343 O 28808 R-3.98882 i 8: - - 1 15 SS 4303 s 2. 3) 8. * }} E33 : GS80 : 4-Me-phenyisulfinic acid

F.G. 8 233T Biotin-SOH (m8} 0 0 1 0.2 8.5 0.8 233 ki. 30 . 330 ... 75

80.

3 ...

20 - Patent Application Publication Jul. 6, 2017. Sheet 6 of 141 US 2017/0192012 A1

F.G. 9

emonoxBioti-SC).ht Hypotaurine (my) 5 50 25 ki 53 88.

37

F.G. 10 Biotin-SOH

NO Donor fa-WA NONOate (nM} 0 1 20 50 00 500

250 k} - 33. 80. Patent Application Publication Jul. 6, 2017. Sheet 7 of 141 US 2017/0192012 A1

FG, Biotin-SOH Biotin-SOH 8 3. 8 s ii. S. 28 kw 233 ki wa 18 wer Sime 38 on 38 as

Sween fSween

58 w Swan

28 w

FG, 2. $3:38xixe:-38ky38 Akira-82cise

s & 8 {

a’ ? u Disciore-aikyte C s? C

: N s {. r 8, C scoo FA&RA-azide

of N-----Y. os---- Y Patent Application Publication Jul. 6, 2017. Sheet 8 of 141 US 2017/0192012 A1

F.G. 3 E g 3: s: Si:3. 3 33 250 kB - " 50 - O. Y- Nhi. 3-iodoacetaficie

w

83 is -2.i

tetramethylrhodamine-5-iodoacetamide (AA-AARA)

FG, 14 1 mM Dimedone 5 mM Ascorbate 1 mM Peroxide sonM No Donor o5 mM Fluorescen-soH 0.5 mM FluorescensoH | | | | s vice ce::::::::: ce:: Patent Application Publication Jul. 6, 2017. Sheet 9 of 141 US 2017/0192012 A1

F.G. S Protein: Human GAPDH, recombinant Peptide: IISNASCTTNCLAPLAK Modification: C = carbamidomethyl, C* =S-S(O)-biotin (thiosulfonate-biotin) Retention Time: 44.70 minutes Drit Tie: 49.36 Betisie Charge: +3 Peptide M+H: 209.9885

y: y :::::sy: y: :: 3 4. S. y2 y:

* - Easthanicionethy: C* : hiosier888-88tin

Patent Application Publication Jul. 6, 2017. Sheet 10 of 141 US 2017/0192012 A1

F.G. 16

ax na go 2. | | | | s g | | | | 5 Protein Description swa s P23919 F & R Thymidylate kinase OOOOO 23 G.O 5 96.79.6 P25685 F & R | DnaJ homolog subfamily B member 1 OOOOO 22 O.OO 5 || 697497 O99428 F & R Tubulin-folding cofactor B OOOOO 20 OCO 5 224745 O9Y2O3 F & R Giutathione S-transferase kappa 1 OOOOO 20 O.OC 5 5545.2 P22090 F & R 40S ribosomal protein S4 00000 6 OOO 6 O.O p3909 F & R 40S ribosomal protein S19 OOOOO 5 O.800 4 205939.5 Q08257 F & R Qinore oxidoreductase 3000.00 5 0.00 A 0.0 Q9Y3B4 F & R | Pre-mRNA branch site protein p14 OOOOO || 4 || 000 || 6 90.383.0 P82244. F & R 40S ribosomal protein S5a OOOOO 13 OOO | 5 || 2471828 Q96CO F & R Protein FAM136A OOOOO 2 OOO 6 66O67.5 63.279 F & R SUMO-conjugating enzyme UBC9 100.00 2 OOO 3 O.O Q9UHC9 F & R NADH-cytochrome b5 reductase 1 100.00 2 0.00 3 O.O PO408O F & R Cystatin-B OOOOO 1 0.08 4 63616.5 Peptidyl-prolyl cis-trans isomerase F, p30405 F & R mitochondria 3000.00 9 O.OC 5 93663.8 P6956 F & R Snai tibiquitin-related modifier 2 3000.00 9 0.00 4 || 10132 Hydroxymethylglutary-CoA lyase, P35914. F & R mitochondria OOOOO 8 0.00 4 O.O 60981 F & R | Desti OOOOO || 8 || 000 4 46415.8 DNA-directed RNA polymerases , , P19388 & R and I subunit RPABC OOOOO 7 0.00 5 O.O Proteasome activator complex subunit Q946 F & R 2 OOOOO || 7 || OOO || 4 || 48029.6 Q15843 8. R NEDD8 1OOOOO 7 OOO 3 73965.8

Q96F2 & R Dynein light chain 2, cytoplasmic OOOOO 7 O.08 3 O.O 18077 F & R 60S ribosomal protein 35a 1OOOOO 5 OOO 5 913.20.8 Q005.26 F & R Cyclin-dependent kinase 3 OOOOO 5 O.00 3 O P55854 F & R Small -related modifier 3 OOOOO 4 OOO 4 O.O Q6EEV8 F&R Small ubiquitin-related modifier 4 OOOOO 4 OOO 4 O.O P300.50 F & R 60S ribosomal protein 12 O7.53 8 O.00 7 || 453842.8 O92526 F & R T-complex protein 1 subunit Zeta-2 55.35 O || 0 || 8 6363.2 Q9Y22 F & R Band 4.-like protein 3 5435 4 O.00 8 3243.3 12532 F & R Creatine kinase U-type, mitochondrial 52.91 8 O08 || 8 5902.0 P48643 F & R T-complex protein 1 subunit epsilon 49.95 12 0.08 8 || 336274.1 Patent Application Publication Jul. 6, 2017. Sheet 11 of 141 US 2017/0192012 A1

FIG. 6 (cont'd) complex protein Nup98 P52948 F & R Nup96 49.75 14 O.O. 8 1565.4 Succinyl-CoA ligase ADP/GEDP p53597 F & R forming subunit alpha, mitochondrial 47.96 6 0.00 | f | 332458.3 C99623 & R Prohibitin-2 46.95 O O.00 8 446.2 p25398 F & R 40S ribosoma protein S12 46.2 14 0.00 || 8 || 48.7315.4 P32969 F & R 60S ribosomal protein 9 45.77 6 O.OO | 7 || 14205.5 Voltage-dependent anion-selective Ch9Y277 F & R channel protein 3 A444 12 O.OO 7 699049 26S proteasome non-ATPase OOO232 F & R regulatory subunit 32 44.25 8 O.OO 8 4211.6 P2A534 F & R Elongation factor 1-beta 43.38 6 O.OO || 8 || 734,476.4 Succinate dehydrogenase ubiquinone 3040 F & R favoprotein subunit, mitochondrial A3.05 9 O.OO | 8 || 27725.30 37.837 F & R Transacolase A2.55 4 O.OO | 8 || 153264 Pyruvate dehydrogenase E1 p 77 F & R component subunit beta, mitochondria 458 24 1.73 | 8 || 1284.75. P43686 F & R 26S protease regulatory subunit 68 A.0.6 8 0.00 | 8 || 220943.6 a 17987 F & R T-complex protein it subunit apha 39.62 3 O.OO | 8 || 40708 X-ray repair cross-complementing 1301 F & R protein 5 39.49 69 1.87 | 8 || 68.350.6 1553 F & R Nucleoside diphosphate kinase A 39.42 20 O.47 8 7488.6 P22392 F & R Nucleoside diphosphate kinase B 39.42 8 O.OO 8 8640.9 Regulator of 87.64 F & R condensation 38.74. 32 3.5 | 8 || 158947.4 4022 F & R T-complex protein it subuhit zeta 38.35 OO 1.62 | 8 || 50533.5 46782 F & R 40S ribosoma protein S5 38.31 4 O.OO | 8 || 28586.O. Ribosoma 1 domain-containing OFSO21 F & R protein 3.95 6 O.OO 8 158260.5 O43778 F & R Asparagine-tRNA ligase, cytoplasmic 37.7A. 6 O.OO | 8 || 0957.8 Putative nucleoside diphosphate O60361 F & R kinase 37.31 4 O.OO 6 56.9 Far upstream element-binding protein GR96AE4 F & R 1 37.07 20 O.OO | 8 || 159148.0 p7355 F & R Annexin A2 36.90 8 O.OO 8 21679. RNA-binding motif protein, X P38.59 F 8: R chronosome 36.63 24 0.00 8 7982O.9 4.6777 F & R 80S ribosoma protein 5 36.36 24 132 || 8 || 332370.3 10 kDa heat shock protein, 6604 r & R mitochondria 35.95 || 1 || 3 || 8 || 24623 O leucine-rich PPR motif-containing P42704 F & R protein, mitochondria 35.89 29 2.06 || 8 || 3O4909.3 P622A1 F & R 40S ribosoma protein S8 35.36 16 5.87 | 8 || 32754.5 Patent Application Publication Jul. 6, 2017. Sheet 12 of 141 US 2017/0192012 A1

FIG. 16 (cont'd)

Acidic elici?e-rich clear P39887 F & R phosphoprotein 32 family member A 3458 4 6.34 || 8 || 395656 Putative pre-mRNA-spicing factor C4343 F & R ATP-dependent RNA helicase DHX15 34.48 6 O.OO || 8 || 61516.8 CO7065 F & R Cytoskeleton-associated protein 4 340 8 OOO || 8 || 175463 p82847 F & R 40S ribosoma protein S24 33.90 24 || 0.00 || 7 || 1382.3 PO7954. F & R Fumarate hydratase, mitochondria 33.90 2 O.OO 7 95793.5 22234 F & R Multifunctional protein ADE2 33.85 54 || 000 || 8 || 1825.82.0 C13838 F & R Spiceosome RNA helicase DDX39B 33.64 90 | 125 || 8 || 284.4444 P3O84. F & R Enoyl-CoA hydratase, mitochondrial 33.32 24 OOO || 8 || 317658.5 Q9UMS4 || F & R. Pre-mRNA-processing factor 19 33.20 O O.OO || 8 || 387.332.8 Heterogeneous nuclear Q1 KMO3 F & R ribonucleoprotein U-like protein 2 33.17 6 O.OO || 8 || 851 12.6 hioedoxin-dependent peroxide P300.48 F & R reductase, mitochondria 32.72 6 2.78 || 8 || 333580.9 ATP-dependent RNA helicase OOO48 8, R DOX39A 32.62 23 || 2.02 || 8 || 2563.002 (504.8 F & R Lysine-tRNA ligase 32.57 6 0.00 || 8 65377.7 PO6744 F & R Glucose-6-phosphate isomerase 32.36 76 168 || 8 || 2372962 P83916 F & R. Chromobox protein honolog 1 32.21 O 0.00 || 8 || 259866

P50395 F & R Rao GDP dissociation inhibitor beta 32.13 28 O.OO || 8 || 173046 trifunctional enzyme subunit alpha, P4O939 F & R mitochondria 32.11 36 || 6 || 8 || 429478.2 P61247 F & R 40S ribosoma protein S3a 3.95 6 OOO || 8 || 1852.O. Q5J V8 F & Ro?sin-1A-interacting protein 3.75 4 COO || 4 || 37626.O P43243 F & R Matin-3 340 53 78 || 8 61497.6 PO9429 F & R High mobility group protein B 30.94 18 8.14 || 7 || 5228.4 p55769 F & R NHP2-like protein 30.77 6 O.OO 2876 43 P28599 F & R Polypyrimidine tract-binding protein 30.60 228 || 1.22 || 8 || 157688.6 Guarine nucleotide-binding protein P63244 F & R sount beia-2-3ike 30.52 20 456 || 8 || 328092.8 Hydroxyacyl-coenzyme A C16836 F & R dehydrogenase, mitochondria 30.49 8 OOO || 6 99.78. CR9Y3EO F & R trNA-splicing Eigase RtcB homolog 3O37 18 OOO || 8 || 41 a97.8 Structural maintenance of O90E7 F & R protein 3 30.33 8 OOO || 8 || 88331.4 P5099. F & R -complex protein 1 subunit theta 30.32 23 1.38 || 8 || 403626.9 P46778 F & R 60S ribosomal protein 21 29.76 6 OOO || 7 || 2864.888 Q8WXX5 F & R DnaJ homolog subfamily C member 9 29.76 4 O.OO || 7 || 1483.6 P7837 F & R -complex protein subunit beta 29.4 90 159 || 8 || 2521.59.6 Patent Application Publication Jul. 6, 2017. Sheet 13 of 141 US 2017/0192012 A1

FIG. 16 (cont'd)

O488 F & R Proteasone subunit alpha type-7 29.72 28 76 || 8 || 427439 P26641 F & R Elongation factor 1-gamma 29.7 38 50 || 8 || 5104.50.9 Eukaryotic translation initiation factor P83241 F & R SA-1 29.7 36 85 || 8 || 27827O.8 36776 F & R on protease homolog, initochondria: 29,70 O 3.44 || 8 || 9383.3 CSP258 F &R Prote RCC2 29.46 9 8 28.057-9 20599 F & R Thioredoxin 29,48 6 8.61 || 8 || 194772.6 P50991 F & R T-complex protein subunit delta 29.44 8 O.95 || 8 || 84.038.9 ATP synthase subunit beta, PO6576 F & Riochonoria 29.30 57 98 || 8 OO181 O95758 F & R Polypyrimidine tract-binding protein 3 29.20 36 O.OO || 4. 0.0 Q4974 F & R lanportin subunit beta-1 29.18 A. COO || 8 || 262272.6 2O700 F & R air-B 28.99 38 5 || 8 || 49572.6 Ras GPase-activating protein-binding Q3283 F & R protein 28.93 5 COO || 6 || 281735.4 P4252 F & R soleucine-tRNA ligase, cytoplasmic 28.72 54 0.00 || 8 || 364962.O. O9Y265 F & R RWB-like 28.57 84 39 || 8 || 19476.6 P99999 F & R Cytochrome C 28.57 O OOO || 8 || 332430.2 054-55 F & R. Lupus La protein 28,57 32 88 || 8 || 382152.2 5358 F & R Coatomer Subunit beta 28.4 4 8.00 || 8 || 33389. Echinodernicrotubule-associated Q9HC35 F & R protein-like 4 28.17 4 COO || 8 || 140932.8 Q04760 F & R actoylglutathione lyase 27.89 24 2.33 || 5 || 67047. Sodium/potassium-transporting P05023 F & R APase subunit alpha- 27.75 66 O.O || 8 || 59045. P39023 F & R 60S ribosomal protein L3 2.74 2 2.23 || 8 || 48744.3.3 Insulin-like growth factor 2 mRNA O9NZ8 F & R binding protein 27.6A OO C.78 || 8 || 25O13. Probable ATP-dependent RNA Q704 r & R helicase DBX46 27.44 6 O.OO || 8 || 39537. P30041 F &R Peroxiredoxi-6 27.39 8 O.00 || 8 || 34309.9 Complement component Q subcomponent-binding protein, CO702 F & R mitochondria 27.29 40 78 || 8 || 8264.853 P08670 F & R Wiretti 27.27 35 2.16 || 8 || 543882.9 Eukaryotic translation initiation factor O6S4 F & R 5A-like 27.23 16 2.15 || 8 O.O Heterogeneous nuclear p8978 F & R ribonucleoprotein K 27.9 93 | 1 || 8 || 188149.5 NAD(P) transhydrogenase, Q3423 F & Ritochondria 27.10 5 3.00 || 8 85989.5 Electron transfer flavoprotein subunit 3804. F & R alpha, mitochondrial 27.00 8 2.41 || 8 || 84.845.O P-512 F & R Adose reductase 26.99 24 O2 || 8 || 2281,765 Patent Application Publication Jul. 6, 2017. Sheet 14 of 141 US 2017/0192012 A1

FIG. 6 (cont'd) O75390 F & R Citrate synthase, mitochondria 26.98 16 COO 8 38886.5 C1585 F & R Postagland: E synthase 3 26.95 6 COO 5 91129.3 C1385 F & R Chronobox protein homolog 3 268 14 OO | 8 || 368542.5 DNA-dependent protein kinase 78527 F & R catalytic subunit 26.80 134 2.08 | 8 || 11 532.7 P53396 F & R ATP-citrate synthase 26.74. 8.00 8 282045 P1588 F & R 40S ribosomal protein S2 26.74 6 8.00 | 8 || 3233.19.0 Q9 Q80 F & R Proliferation-associated protein 2G4 2659 || 48 63 || 8 || 355385, Heterogeneous nuclear 55795 F & R ribonucleoprotein H2 26.52 18 63 8 880304 Heterogeneous nuclear P51991 F & R | ribonucleoprotein A3 26.5 46 0.63 || 8 || 2488948 p27797 F & R Caeticulin 26.39 28 5.22 | 8 || 59856.6 p6271 F & R 40S ribosonal protein S4, X isoform 26.29 2O .00 | 8 || 256997.4 P82424. F & R 60S ribosomal protein L7a 26.28 14 7.38 7 179C958 O75369 F & R Fianni-B 26.8 || 204 000 || 8 19264.8 PA 219 F & R Peripherin 26,02 18 O.OO 8 O.0 Cysteine and histidine-rich domain Q9UHD1 F & R containing protein 26. 26 8.00 | 8 || 124698.9 O08945 F & R FACT complex subunit SSRP1 25.58 19 64. | 8 || 237266.9 Heterogeneous nuclear PA 866 F & R ribonucleoprotein L 25.34 15C O9 | 8 || A270556 P494.1 F & R Etongation factor Tu, mitochondria 25.32 || 56 154 | 8 || 496,806 C925 F & R leucine--tRNA ligase, cytoplasmic 25.22 || 34 O.OO | 8 || 352493.5 P3899 F & R Eukaryotic initiation factor 4A-1 25.9 .63 8 88626.5 Q99798 F & R Aconitate hydratase, mitochondria 25.13 49 O7 | 8 || 3872O1 POO558 F & R Phosphoglycerate kinase 1 25.11 73 2.34 8 63995O Probable ATP-dependent RNA P7844 F & R helicase DOX5 25.00 6 COO 8 97.277.5 P55060 F & R Exportin-2 2460 2O O.OO | 8 || 13518 ASNH2 F & R tubulin alpha chain-like 3 2A47 2O C.72 7 O.O P4250 F & R Glycine-tRNA ligase 24.46 11 O.OO | 8 || 163329.2 Signal recognition particle subunit OF8094. r &R SRP72 2445 || 24 2.8 8 3842.8 P28839 F & R threonine-tRNA ligase, cytoplasmic 24.29 52 .06 | 8 || 1235.835 P3948 F & R Stress-induced-phosphoprotein 24.22 52 .29 | 8 || 654334.8 7237 F & r | Protein disfide-isomerase 24. 25 57 8 215588 P5692 F & R Methionine-trA ligase, cytoplasmic 24.10 5 24 8 15018.7 3243 F & R E1B protein, large T-antigen 24.04 54 45 | 8 || AA-26962 Splicing factor, proline- and glutamine P23246 F & R rich 23.74 124 O.85 | 8 || 315609.7 P53675 F & R Cathrin heavy chain 2 23.64 8 COO 8 O.O P26.583 F & R High nobility group protein B2 23.52 4 3.15 8 31 O988.7 Patent Application Publication Jul. 6, 2017. Sheet 15 of 141 US 2017/O192012 A1

FIG. 6 (cont'd) C2906 F & R interleukin enhancer-binding factor 3 23.50 36 0.39 8 75520.7 Heterogeneous nuclear O60506 F & R ribonucleoprotein Q 23.4 266 0.38 8 98.132.0 P6204 F & R ADP-ribosylation factor 3 23.24. 14 OCC 8 O.O P84077 F & R ADP-ribosylation factor 23.24. 14 0.00 8 69385.9 O3244 F & R EB 55 kDa protein 236 44 34 8 205845.8 Dihydrolipoyl dehydrogenase, PO9822 F & Ritochondria 2334 8 OOO 6 19597.6 Bifunctional glutamatelproline-tRNA PO7814 F & R tigase 23.3 64 4.72 | 8 || 34.245 Heterogeneous nuclear O4979 F & R ribonucleoprotein D-like 23.03 6O O.OO 8 13213 Heterogeneous nuclear 52597 F & R ribonucleoprotein F 22.77 24 119 8 278383.5 C 4257 & R Reticulocabin-2 22.76 16 2.28 8 368211.9 Q6P2C9 F & R Pre-mRNA-processing-spicing factor 8 22.76 22 || 8 || 8 || 12000.3 Peptidyl-prolyi cis-trans isomerase CROO688 F & R FKBP3 22.70 13 129 8 448645.6 Q15393 F & R Splicing factor 3B subunit 3 22.61 12 O.CO 8 89743.1 PO541 F & RADPATP traSocase 2 22.44 31 2.97 || 8 || 277247. Q99832 F & R T-complex protein subunit eta 224 68 O,O || 8 || 203029.9 p82081 F & R 40S ribosonal protein S7 2232 3 134 7 347785.7 Heterogeneous nuclear COO839 F & R ribonucleoprotein U 22.31 144 185 8 38.1082 P 940 F & R Polyadenylate-binding protein 1 22.9 14 453 3 34.427.7 KH domain-containing, RNA-binding, signal transduction-associated protein CO7666 8, R 229 26 OOO || 8 || 209558.2 O43707 F & R Alpha-actinin-4 22.5 62 133 || 8 || 387256.7 60 kDa heat shock protein, 0809 F & R mitochondria 22.30 170 08 || 8 || 2330.92.8 3929 F & R Beta-enolase 22.08 96 32 || 8 60880.5 CR3162 F & R Peroxiredoxin-4 2.94. 17 106 || 8 || 302684.5 18124 F & R 60S ribosonal protein L7 21.93 10 2.36 7 O9397.7 DNA-(apurinic of apyrimidinic site) P27695 F & R lyase 21.87 10 000 || 8 || 2:23970.9 P60842 F & R Eukaryotic initiation factor 4A- 21.82 34 162 8 97.367.7 p : 71 F & R Protein 41 2.79 22 O.OO || 8 4,6830.2 26S proteasome non-ATPase 9.9460 F & R regulatory subunit 21.73 28 OOO 8 93678.9 Lamiina-associated polypeptide 2, p42.67 F & R isoforms beta/gamma 2172 62 23 8 F74.441 Lamina-associated polypeptide 2, PA288 F & R isoform alpha 2171 32 2.21 8 8696.5 Patent Application Publication Jul. 6, 2017. Sheet 16 of 141 US 2017/0192012 A1

FIG. 6 (cont'd)

P4O925 F & R Malate dehydrogenase, cytoplasmic 2.84 69 22 || 8 || 152817.2 P27824 F & R Calnexin 253 28 57 || 8 || 33.9747.7 Sodium/potassium-transpoiting P 3637 F & R A Pase subunit alpha-3 244 6 O.OO || 8 O.O Sodium/potassium-transporting P5O993 F & R A Pase subunit alpha-2 244 6 OOO | 8 || 201986.5 CR02878 F & R 60S ribosomal protein L6 233 22 2.56 | 8 || 7929O. Hypoxanthine-guanine POO492 F & R phosphoribosyltransferase 2.38 10 OOO | 8 || 162222.2 CROOSO F & R Clathrin heavy chain 21.28 || 72 439 || 8 || 70410.7 Q9NYF8 F&R BC-2-associated transcription factor 1 2.27 92 158 8 7415.8 X-ray repair cross-complementing P12956 F & R protein 6 2.8 73 135 | 8 || 5198496 C914 F & R Gamma-enoiase 20.94 28 2.5 | 8 || 238063.6 O43660 F & R Pleiotropic regulator 20.82 8 O,OO || 6 38530.5 P62826 F & R GTP-binding Ran 255 8 OOO | 8 || 49903O. OOC567 F & R Nucleolar protein 56 20.40 9 O.OO | 8 || 3O807.5 Q4697 F & R Neutral alpha-glucosidase AB 2039 || 48 OOO | 8 || 3475.6 Exosome complex exonuclease QY21 & R RRP44 20.6 A O.OO || 8 91708.4 CO6830 & R Peroxiredoxin- 20.4 39 165 | 8 || 632437.6 P43487 F & R Ran-specific GTPase-activating protein 20.04 O O.56 | 8 || 485,792.8 P82995 F & R Transformer-2 protein homolog beta 19.85 28 O.32 | 8 || 624.27.4 CR6PEY2 F & R Tubin alpha-3E chain 1984 || 108 O.95 8 553644. Ubiquitin-like modifier-activating P22314 F & R enzyme 1 9.78 69 O.86 | 8 || 66.9519.9 Putative heat shock protein HSP 90 Q58FF F & R beta-3 9.74 16 2.53 8 O.O 12277 F & R Creatine kinase B-type 9.70 || 90 109 | 8 || 84098 PO7737 & R Profit-1 1989 38 1.36 | 8 || 393427. CB08043 F & R Alpha-actinin-3 1983 6 89 8 O.O Pi3867 F & R Protein disulfide-isomerase A4 1953 35 O.OO || 8 || 331324.7 Plasminogen activator inhibitor 1 RNA C8NC51 F & R binding protein 9.4 88 O.OO | 8 || 1617675 P6O709 F & R Actin, cytoplasmic 1 1934 28 O.94 | 8 || 86.32638 63261 F & R Actin, cytoplasmic 2 19.34 28 O.94 | 8 || 56143.4 4618 F & R Pyruvate kinase PKM 923 || 32 O,44 || 8 || 3785.559 Heterogeneous nuclear 31943 F & Ribonucleoprotein H 8.96 54 0.68 || 8 || 59420.7 C3748 F & R Tubulin alpha-3CD chain 8.96 || 220 0.68 || 8 || 184392.2 C14498 F & R RNA-binding protein 39 18.90 38 O.OO 8 77.385.O 236578 F & R 60S ribosomal protein L4 8.79 40 166 | 8 || 356.685.O Patent Application Publication Jul. 6, 2017. Sheet 17 of 141 US 2017/0192012 A1

F.G. 6 (cont'd) Structural saintenance of Q9M3 F & R chromosomes protein 4 8.73 12 O.OO || 8 69339.5 PO4350 F & R buin beta-4A chain 1870 3C 1.68 || 8 425344 Heterogeneous nuclear O43390 F & R ribonucleoprotein R 8.42 2 O.95 || 8 27.775.9 Heterogeneous nuclear 1315 F & R ribonucleoprotein AO 8.4 18 5 || 8 || 4792.45.3 Putative elongation factor 1-alpha-like CSVO & R 3 18.36 O3 28 || 8 O.O PS84. F & R Etongation factor 1-alpha 8.36 || 103 28 || 8 || 86.2416 OOC57 F & R ATP-dependent RNA helicase DDX3X 18.30 34 0.50 || 8 32553.3 O5523 F8 RATP-dependent RNA helicase DDX3Y 1830 15 O.OO || 8 9968, 62753 F & R 40S ribosoma protein S6 8.28 12 0.74 || 7 || 3999.340 Heterogeneous nuclear CR14103 F & R ribonucleoprotein DO 1809 || 144 8.72 || 8 || 74885.1 6837 F & R Tibeta-4B chain 17.99 || 52 84 || 8 || 32685.3 Q9GZL7 || F & R Ribosome biogenesis protein WDR 12 1795 4 O.OO || 8 || 589719 P54818 F & R Adenylate kinase 2, mitochondria 7.6 134 0.00 || 8 54378,3 P3569 F & R Alpha-actinin-2 7.53 20 38 || 8 38678 C4247 F & R Scshstrate contactin 1740 || 48 O.OO 8 74213.7 P68366 F & R Tubusin alpha-4A chain 17.26 82 O.95 || 8 4746.0 PO795 F & R. L-lactate dehydrogenase 8 chain 724 73 1.25 || 8 || 6821670 p13639 F & R Eongation factor 2 1723 93 158 || 8 || 599956.8 CR9BWA1 || F8 R bui beta-2B chain 17.16 || 46 30 || 8 || 4.71332 Q005 8, R Protein SE 7. 126 0.59 || 8 || 284922.9 Heterogeneous nuclear Q99.729 F & R ribonucleoprotein AB 17.07 20 0.76 || 8 || 44794.7 397 r & R Pastin-3 17.84 14 9.03 || 8 || 2:38:12.5 Q5JRX3 F & R | Presequence protease, mitochondria 1704 12 O.OO || 8 18300 Q15366 F & R Poly(C)-binding protein 2 16.99 || OO O.72 || 8 || 47689.8 Glyceraldehyde-3-phosphate P04406 F & R dehydrogenase 16.96 96 0.92 || 8 || 1381156.7 C562R F & R Beta-actin-like protein 2 8.82 34 95 || 8 O.O P68032 F & R Actin, alpha cardiac muscle 1 16.62 56 127 | 8 O.O PS2F36 F & R Actin, aortic smooth muscle 6.82 54 27 | 8 366.3 O9NY65 F & R Tubusin alpha-8 chain 6.59 32 0.74 || 8 O.C. Putative heat shock protein HSP 90 O58FG | F& Ralpha A4 652 18 .96 || 8 O.O. Q05639 F & R Ekongation factor 1-alpha 2 6.48 69 20 || 8 97.902.8 63267 F & R Actin, gamma-enteric smooth muscle 6.48 92 0.95 || 8 || 43O886.9 Q13509 r & R Tbi beta-3 chair 1846 38 30 || 8 || 989. 6.353 F & R 60S ribosoma protein 27 16.4 6 O.OO || 6 777360 Patent Application Publication Jul. 6, 2017. Sheet 18 of 141 US 2017/0192012 A1

FIG. 16 (cont'd) Probable ATP-dependent RNA O92841 F & R helicase DDX17 16.37 150 O.35 | 8 87835.8 ATP synthase subunit alpha, p25705 F & R mitochondria 16.37 64 2.41 8 263868.1 PO9874. F & R Poly ADP-ribose polymerase 1 1636 154 0.64 || 8 || 94.8426.9 C15365 F & R Poly(rC)-binding protein 1 16.33 32 125 || 8 || 34.7636.3 PO8107 F & R Heat shock 70 kDa protein 1A11B 16.31 150 O.83 || 8 || 2754316 C13885 F & R Tubulin beta-2A chain 16.31 42 128 || 8 || 196596.1 Putative high mobility group protein B2RPKO & R B-like 1 6.31 8 2.34 || 7 || 1796O2.3 POTE ankyrin domain family member O6S83 & RE 16.15 44 1.72 || 8 47525.4 57721 F & R Poly(rC)-binding protein 3 16.14 60 0.91 || 6 O.O Heterogeneous nuclear P52272 F & R ribonucleoprotein M 16.10 134 181 8 203756.O Heterogeneous nuclear P22626 F & R ribonucleoproteins A2/B1 16.04 || 178 0.64 || 8 || 342445.4 POO338 F & R L-lactate dehydrogenase A chain 15.99 || 193 0.49 || 8 | 189002 P6O174 F & R Triosephosphate isomerase 15.96 || 134 O.79 || 8 286432.4 PO8238 F & R Heat shock protein HSP 90-beta 15.70 | 122 0.91 || 8 | 844884.1 p54577 F & R Tyrosine-tRNA ligase, cytoplasmic 5.63 48 1, 15 || 8 || 4225694 PO4O75 F & R Fructose-bisphosphate aldolase A 15.61 38 1.OO || 8 || 6383O4.5 P63104 F & R 14-3-3 protein zeta delta 15.57 52 0.99 || 8 || 552340.2 p19338 F & R Nucleolin 15.40 || 103 100 || 8 || 887612.5 Activated RNA polymerase II P53999 F & R transcriptional coactivator p15 15.34 4. O.OO || 6 94.1990 Putative heat shock protein HSP 90 O58F-6 F & R beta 4 15.23 10 O.OO || 8 O.O P68363 F & R Tubulin alpha-1B chain 15.18 152 O.85 || 8 11503.3 Peptidyl-prolyl cis-trans isomerase OO2790 & R FKBP4. 15.14 26 4.54 || 8 || 373971.O O71U36 F & R Tubulin alpha-1A chain 15.09 || 150 O.89 || 8 || 1146962.8 CO8211 F & R ATP-dependent RNA helicase A 1487 || 102 488 || 8 || 377O78.6 Peptidyl-prolyl cis-trans isomerase A O9Y536 F & R like 4A/B/C 1482 12 O.OO || 8 O.O P4O429 F & R 60S ribosomal protein L13a 14.70 12 0.26 || 7 | 20717.1 Putative 60S ribosomal protein L13a O6NWW1 & R like MGC87657 14.70 12 0.26 || 7 || 412753.5 O0817O F & R Serine/arginine-rich splicing factor 4 14.64 14 122 || 8 558O3.6 Non-POU domain-containing octamer O15233 F & R binding protein 1459 22 0.09 || 8 | 16.77419 PO6748 F & R Nucleophosmin 1446 148 117 | 8 || 272666.O Q9BQE3 F&R Tubulin alpha-1C chain 1438 || 130 O.87 || 8 | 66O524.1 Patent Application Publication Jul. 6, 2017. Sheet 19 of 141 US 2017/0192012 A1

FIG. 16 (cont'd)

PO790 F & R heat shock protein HSP 90-alpha 3.68 272 || 0.39 || 8 || 358835.9 P3493; F & R Heat shock 70 kDa protein -ike 13.61 47 | 1.24 8 8663.3 CRO 130 F & R Serinefarginine-rich spicing factor 2 13.52 9 || O.OO | 8 || 08786.2 PS2937 F & R Peptidy-prolyl cis-trans isomerase A 3.43 64 || O,94 || 8 || 653908. RNA-binding protein with serine-rich C15287 F & R domain 3.37 36 | 1.8 | 8 || 04692.3 PO6733 F & R Alpha-enolase 3.6 292 | 1.07 || 8 || 65030.7 P23528 F & R Cofilin- 3.12 37 || 4.05 || 8 || 6883 4.5 p4.6776 F & R 60S ribosomal protein .27a 3.03 15 || 0 || 8 || 39.7424.9 P38646 F & R Stress-70 protein, mitochondria 12.90 6 2.83 || 8 || 64542O3 P4959 F & R Serine-tRNA tigase, cytoplasmic 2.51 13 OOO | 8 || 27.13615 POCG38 F & R POTE ankyrin domain family member 1167 8 O.76 || 8 || 73131.0 POTE ankyrin domain family member POCG39 8. R 1.67 8 || O.76 8 O.O Heterogeneous nuclear C32251 F & R ribonucleoprotein A-like 2 64 60 | 1.82 8 64713.1 Heterogeneous nuclear PO965 F & R ribonucleoprotein A1 1.59 234 || O.86 | 8 || 267,197.6 Putative heat shock protein HSP 90 CR58FF8 F & R beta 2 1.3 28 || 0.46 || 8 O.O. P17066 F & R heat shock 70 kDa protein 6 104 32 || 0.82 8 0.0 PO7437 F & R Tibutin beta chain O3 70 2.74 | 8 || 72O238.8 P1 O2 F & R 78 kDa glucose-regulated protein OO 89 | 1.73 || 8 || A93882.5 Q9'Y281 F & R COfilin-2 0.96 18 1.5 | 8 || 48686.6 CR9YS17 F & R Phosphoserine aminotransferase 0.85 70 2.17 | 8 || 196697.6 Programmed cell death 6-interacting Q8WUM4 F & R protein 0.85 8 O.OO 8 77595.7 O4375 F & R D-3-phosphoglycerate dehydrogenase 10.76 70 || 153 || 8 || 494O25.

P4874 F & R Putative heat shock 70 kDa protein 7 10.57 18. O.OO 8 796.03.7 POTE ankyrin domain family member A5A380 F & R F 0.48 22 || 0.31 8 O.O P6133 F & R 60S ribosoma protein 5 0.33 28 || O.60 | 8 || 25989.7 CRO7028 F & R 60S ribosomal protein 18 0.33 11 O.OO | 7 || 2:10955.3 PO7864 F & R -lactate dehydrogenase C chain 30.23 9 || O.O.3 7 O.O P54652 F & R Heat shock-related 70 kDa protein 2 0.21 61 O.46 || 8 0.0 P38 O F & R Protein disfide-isomerase A3 0.19 46 2.88 || 8 || 510283.3 Putative heat shock protein HSP 90 CR 14568 F & R alpha A2 O.O2 2O || O.9 8 0.0 Q9BYX7 F & R Putative beta-actin-like protein 3 9,97 18 O. 1 8 58244.6 Q16576 F & R Histone-binding protein RBBP7 9.73 28 || O.OO 8 18807.3 P14625 F & R Endoplasmin 9.57 41 2.23 || 8 || 272594.5 Patent Application Publication Jul. 6, 2017. Sheet 20 of 141 US 2017/0192012 A1

FIG. 16 (cont'd) OO9028 F & R | Histone-binding protein RBBP4 950 75 O.49 8 793 13.5 P16152 F & R Carbonyl reductase NADPH 1 9.23 14 || 4.36 8 165216.5 Putative heat shock protein HSP 90 Q58FGO F & R alpha A5 922 1O O.OO 8 O.O P62979 F & R Ubiquitin-40S ribosomal protein S27a 8.96 30 O.78 8 712462.4 Trifunctional purine biosynthetic P22102 F & R protein adenosine-3 8.48 46 O.OO 8 155187.6 P21333 F & R | Flamin-A 8.43 64 || 2.61 || 8 75969.4 P477.56 F & R F-actin-capping protein subunit beta 841 6 O.OO 6 33959.8 C-1-tetrahydrofolate synthase, P11586 F & R cytoplasmic 836 26 3.3O 8 321699.1 C13642 F & R Four and a half LIM domains protein 1 8O1 352 108 8 1713698 P42766 F & R 60S ribosomal protein L35 7.52 12 O.19 6 124,166.3 P62987 F & R Ubiquitin-60S ribosomal protein L40 7.28 2O | O.23 || 8 | 165775.2 P4O926 F & R Malate dehydrogenase, mitochondrial 7.07 71 2.85 8 860861.9 P12814 F & R Alpha-actinin-1 661 96 162 8 284O2.5 P 13796 F & R Plastin-2 6.37 4. O.OO 5 O.O Q5T4S7 F & R E3 ubiquitin-protein ligase UBR4 5.73 13 O.OO 8 O.O Sister chromatid cohesion protein Q29RF7 F & R | PDS5 homolog A 503 6 O.OO 6 4978.1 O7Z406 R Myosin-14 52.91 10 O.OO 4 1959.8 Heterogeneous nuclear O8WWW9 R ribonucleoprotein L-like 51-55 8 OOO 3 AO622.6 On 12905 R Interleukin enhancer-binding factor 2 51.28 4. O.26 4 356718.9 H/ACA ribonucleoprotein complex O60832 R subunit 4 50.25 8 8.84 4 106975.6 Deoxyuridine 5'-triphosphate P33.316 R nucleotidohydrolase, mitochondrial 49.75 4. O.OO 3 46 128.0 Dolichyl-diphosphooligosaccharide-- PO4844 R protein glycosyltransferase subunit 2 49.51 8 2.94 4 40817.1 P45974 R Ubiquitin carboxyl-terminal hydrolase 5 49.51 4. OOO 4 50453.9 P087.08 R 40S ribosomal protein S17 49.14 4. 3.85 4 O.O POCW22 R 40S ribosomal protein S17-like 49.14 4. 3.85 4 159867.5 Bifunctional purine biosynthesis protein P31939 R PURH 48.21 24 3.49 4 228110.1 P11532 R Dystrophin 4785 4 O.OO 3 O.O PO9960 R Leukotriene A-4 hydrolase 47.72 52 182 4 591812 P08133 R Annexin A6 47.62 4 O.OO 4 55652.1 O9UJZ1 R Stomatin-like protein 2, mitochondrial 4728 4. 3.12 3 153625.1 P27361 R Mitogen-activated protein kinase 3 45.66 12 | 1.67 4 4305.9 CO3252 R Lamin-B2 44.64 4 || 1056 || 4 || 2277417 U1 small nuclear ribonucleoprotein 70 PO8621 R kDa 44.52 30 O.99 4 37190.5 Patent Application Publication Jul. 6, 2017. Sheet 21 of 141 US 2017/O192012 A1

FIG. 16 (cont'd)

P48047 R ATP synthase subunit O, mitochondrial 44.12 6 2.92 4 194773.O C96EP5 R DAZ-associated protein 1 43.8 16 3.07 4 76092.8 C16543 R Hsp90 co-chaperone Codc37 42.92 4. 4.42 4 195857.5 Sarcoplasmic/endoplasmic reticulum C93084 R Calcium ATPase 3 42.49 42 181 4 O.O Pyruvate dehydrogenase E1 Component subunit alpha, Somatic P08559 R form, mitochondrial 42.37 40 2.16 4 44270.4 O5BKZ1 R DBIRD complex subunit ZNF326 41.99 12 O.71 3 2010O.O Eukaryotic translation initiation factor 3 O9Y262 R Subunit 41.24 8 0.68 4 68600.3 O9Y2X3 R Nucleolar protein 58 4.1.24 4. 5.60 4 158569.9 P62195 R 26S protease regulatory subunit 8 40.98 16 3,53 4 7 1898.9 6-phosphogluconate dehydrogenase, P52209 R decarboxylating 40.46 12 197 | 4 || 284.433.1 P25789 R Proteasome subunit alpha type-4 40.08 4. 2,08 3 132262.9 Phosphatidylinositol transfer protein P48739 R beta isoform 40.00 8 2.72 4 280516 Mitochondrial import receptor subunit O94826 R TOM70 39.76 4. 9.94 4 19046O.O P05388 R 60S acidic ribosomal protein P0 39.37 4. 140 4 91241.6 Serine-threonine kinase receptor O9Y3F4 R associated protein 38.65 8 7.46 4 || 1995O4.3 CR 15181 R Inorganic pyrophosphatase 37.61 16 3.54 4 || 371334.5 Aldehyde dehydrogenase X, P3O837 R mitochondria 36.90 8 2.32 4 612894 Structural maintenance of C14683 R chromosomes protein 1A 36.81 6 12.18 4 19928O.3 O924.99 R ATP-dependent RNA helicase DDX1 36.62 42 161 4 309.376.6 O43583 R Density-regulated protein 36.50 4. 4.26 3 108589.4 P35749 R Myosin-11 36.45 2A 1.73 4 146.4 Apoptotic condensation O9 JKV3 R inducer in the nucleus 36.19 24 O.39 4 75767.3 O14739 R Lamin-B receptor 36.17 4. 2.09 | 3 || 376780.8 O15020 R Spectrin beta chain, non-erythrocytic 2 36.1O 4. O.OO 4. 255.O P.11277 R Spectrin beta chain, erythrocytic 36.10 6 O.OO 3 O.O tRNA (cytosine(34)-C(5))- Q08J23 R methyltransferase 36.06 6 4.04 4 || 46568.8 Ribose-phosphate pyrophosphokinase P60891 R 1 35.34 4. 1.25 | 4 || 1326732 Phosphate carrier protein, QOO325 R mitochondria 34.66 8 1.92 3 90756.3 Patent Application Publication Jul. 6, 2017. Sheet 22 of 141 US 2017/0192012 A1

FIG, 16 (cont'd)

Acidic leucine-rich cear O43423 R phosphoprotein 32 family member C 34.52 6 2.62 4 O.O CR356 R Dynactin subunit 2 34.48 6 OOO 4 57342 p862 R 60S ribosoma! protein L17 34.44 12 2.61 4 183690 S-methyl-5'-thioadenosine CR 1328 R phosphorylase 34.44 42 O59 3 14563.6 P35998 R 26S protease regulatory subunit 7 34.36 A O.2 4 || 40834.7 Acetyl-CoA acetyltransferase, P24752 R mitochondria 34.03 2 185 4 || 305446.6 53-2 R Acylglycerol kinase, mitochondrial 33.98 6 2.31 4 9511. 16 kDa U5 smal nuclear O15029 R ribonucleoprotein component 33.93 16 2.9 | 4 || 123489.O C14315 R Fiat-C 33.22 8 0.55 4 3883 Ribose-phosphate pyrophosphokinase 1908 R 2 33.22 A OOO 3 O.O. Aldehyde dehydrogenase, PC5091 R hitochondria 32.87 2.49 A 152860. C1681 R Septin-7 32.77 12 129 3 58984.7 P1766 R Alcoho dehydrogenase class-3 32.3 A. O.54 4 || 3141674 Ubiquitin carboxyl-terminal hydrolase PO9936 R isozyme L1 32.73 A 1848 4 183465.3 Q9X6 R A-kinase anchor protein 8-like 32.57 4 OOO 4 || 37328.9 C9Y539 R FACT complex subunit SPS 16 32.43 19 2.11 4 || 36558.0 (13618 R Culin-3 32.36 8 OOO 3 1865 Sarcoplasmiciendoplasmic reticulum 665 R Calciun APase 2 32.28 46 198 4. 182816 O94906 R Pre-mRNA-processing factor 6 32.26 4 OOO a 15O18.8 Mitochondriat 10-formyltetrahydrofolate C3SY69 R dehydrogenase 32.2 A 36 || 4 || 130633.6 OOO15 R PDZ and LM domain protein 32.15 A 2.07 || 4 || 19.0997.7

C13427 R Peptidyl-proly cis-trans isomerase G 32.1 8 O.21 4 2402.5 PS1964 R WD repeat-containing protein 5 32.09 8 6.7 4 3766O7 Aminoacyl tRNA synthase complex O12904 R interacting nultifunctional protein 1 397 16 1.2 | 4 || 188586.0

608 R NEDD8-conjugating enzyme Ubc12 31.9 4 O.41 4 205056.4 Heat shock protein 75 kDa, CR 1293 R mitochondria 31.79 13 111 || 4 || 18805.9 Putative RNA-binding protein luc7-like O9NQ29 R 1 31.75 12 0.91 3 373473 Medium-chain specific acyl-CoA 131 R dehydrogenase, mitochondria 3.75 4. OOO 3 65743.6 Patent Application Publication Jul. 6, 2017. Sheet 23 of 141 US 2017/0192012 A1

FiG. 16 (cont'd) P623O4. R Snail nucleaf ribonucleopotein E 31.70 4. OOO | 3 || 284.97.9 -inducing factor 1, O9583 R mitochondria: 366 20 170 4 6O742.3 C 14157 R Ubiquitin-associated protein 2-like 3155 O 0.00 4 26540.5 O15355 R Protein phosphatase G 3.25 4. 137 3 82O74. Serine hydroxymethyltransferase, P34897 R titochocia: 31.18 48 0.58 A 66454.8 28. R Capastatin 31,06 32 O.19 A 36614 O3557 R Heat shock 70 kDa protein 4 3O89 20 29 a 1424.8 C9NR45 R Static acid synthase 30.86 16 2.57 4 285,372.7 Actin-related protein 2/3 complex O 1545 R subunit 3 3O82 4. 28 3 3233.7 53E 6 R Programmed ceil death protein 4 30.77 8 O9 3 4858.5 C9G2S3 R WD repeat-containing protein 6 30.72 4. 14 3 46676.3 P798 R 26S protease regulatory subunit 6A 30.64 3. O.85 4. 8O86. P35580 R Myosin-80 3O37 44 0.83 4 65354.5 C9. G8 R estin 30.29 4 156 a | 10308.6 Q92878 R DNA repair protein RAD50 3O2 6 COO 4 || 51889 P49368 R -complex protein 1 subunit gamma 30, 16 26 O.73 4 || 178761.5 1423 R Dynactin subunit 29.94 20 0.09 4 20929.7 P3004.4 R Peroxiredoxin-5, mitochondria 29.84 36 36 4 36364 P8989 R Y-box-binding protein 3 29.79 8 0.09 4 58330.7 Nuclease-sensitive element-binding P87809 R protein 1 29.79 6 18 4 || 9065. Ogy27 | R Y-box-binding protein 2 29.79 6 0.18 4 || 109255.5 89Y490 R an 29.67 6 493 || 4 || 11577.O. C99497 R Protei DJ- 29.64 10 2.64 a || A6531A.4 Ch994.59 R Cell division cycle 5-like protein 2960 5 447 A 481.9 PO4637 R Cellular tumor antigen p53 29.50 2 COO 3 258.4 Acidic leucine-rich nuclear Q93: R phosphoprotein 32 family member E 29.44 6 0.89 3 59a 19.1 CR.3620 R C-4B 29.4 6 OOC 4. 19926.3 CR9Y2BO R Protein canopy homolog 2 29.4 8 0.43 3 52874.7 CR.369 R Culin-4A 29.4 4. OOO 3 8. C930 R SUMO-activating enzyme subunit 1 29.40 18 104 4 91909.5 O004 R importin-5 29.33 6 0.80 3 440.4 Pasha rebrae calcium P23634. R transporting ATPase 4 29.6 6 0.30 4 2584.8 Pasna terribrarie Calcin P2C2O R transporting ATPase 1 29, 16 2 0.00 4 657.4 Pasna errorarie Calciuri CO84 R transporting ATPase 2 29, 16 16 COO 3 8O Patent Application Publication Jul. 6, 2017. Sheet 24 of 141 US 2017/0192012 A1

FIG. 6 (cont'd) Pasna nembfare calcium O872O R transporting ATPase 3 29, 16 6 O,OC 3 O.O. Probable A P-dependent RNA P28398 R helicase DDX6 29, 16 6 3.49 3 9454-9 Serrate RNA effector molecule C98x5 R honolog 29.02 50 O.S 4 584504 OR8A2 R SWISNF complex subunit SMARCC2 28.94 2 O. 17 | 3 32606.5 C92922 R SWI/SNF complex subunit SMARCC1 28.94 A. 0.34 3 4626.5 Far upstream element-binding protein C929.45 R 2 28,20 6 2.30 4 3703448 P39748 R Flap endonuclease 1 28.13 8 2.69 4 224.725.4 Phosphatidylethanolamine-binding P30086 R protein 1 27.98 8 49 || 4 || 515799 P35268 R 60S ribosomal protein 22 27.70 4. 2.07 || 3 | 152828.0 Q1287.4 R Splicing factor 3A subunit 3 27.57 6 357 4 23208.6 P3563 R Basigin 27.32 6 314 3 51734 ATP-binding cassette sub-family E P822 R member 27.32 4. 5.90 3 O2O854 Q15717 R EAV-ike protein 27.5 6 5.68 3 62385.6 U5 smal: nuclear ribonucleoprotein 200 O75643 R KDaeicase 27.12 50 | 0 || 4 || 18338.0 PO2545 R Preahir-AfC 27.03 6 343 4. 76.1586 Glyoxalase domain-containing protein Q9HC38 R 4 26.88 8 O.00 3 47269.7 Eukaryotic translation initiation factor 2 PA O9. R subunit 3 26.74 4 2.93 3 3.3087. Of 97 R Neurofilament medium polypeptide 26.70 36 85 A. 18804.7 C9B225 R Apoptosis inhibitor 5 26.4 30 0.63 4 6348.7 Spermatid perinuclear RNA-binding Q96S9 R protein 26.28 32 45 4 89.146 P46060 R Ran GTPase-activating protein 26,28 A. 7.24 3 O9896. P284.82 R Mitogen-activated protein kinase 1 26, 13 6 7.10 || 4 || AA539.6 Transitional endoplasmic reticulum P5502 R APase 28.02 40 3.86 4 3877O4. P531 R E2 25.57 2 0.92 4 27798.O insulin-like growth factor 2 mRNA C9Y6M1 R binding protein 2 25.46 72 0.52 4. 543.6 P3,948 R 14-3-3 protein beta-alpha 25.44 48 20 4 5073.9 P4932 R Nuclear autoantigenic spern protein 25.36 26 09 || 4 || 09085.5 P23381 R Tryptophan-tRNA tigase, cytoplasmic 25.9 2 33 4. 63667.1 Thioredoxin domain-containing protein Q8NBS9 R 5 25.9 4. COO 3 13708.3 Ras GTPase-activating-like protein P46940 R OGAP 25.16 8 O70 4 39403,3 Patent Application Publication Jul. 6, 2017. Sheet 25 of 141 US 2017/0192012 A1

FIG. 6 (cont'd) p0918 R Carbonic anhydrase 2 25.1 28 2 || 4 || 54685.8 Q9YSA9 R YTH domain family protein 2 25,06 4 8.00 || 3 2466-0 Ch92598 R Heat shock protein 105 kDa 25.05 42 44 || 4 42060.4 P62906 R 60S ribosomal protein L10a 25.04 6 1.9 || 3 || 57.435.1 Voltage-dependent anion-selective P21796 R channel protein 24.9 8 3.99 || 4 || 204664.8 P12036 R Neurofilament heavy polypeptide 249s 2 99 || 3 O.O PO796 R Neurofilament light polypeptide 24.96 6 2.99 || 3 O. 17661 R Desfin 24.96 S 2.99 || 3 OO Transcription elongation factor A P2393 R protein 24.95 16 68 3 705074 P37802 R Transgelin-2 24.83 5 2.6 || 3 || 422672.5 O9Y4 R Hypoxia up-regulated protein 1 248 6 0.99 || 4 || 22059.2 Ch9JES4 R DnaJ honolog subfamily B member 1 24.75 4 165 || 3 || 191436 O1498O R Exportin-1 24.59 17 139 || 4 || 123463,3 O75083 R WD repeat-containing protein 2440 || 8 || 4.94 || 4. 83521 Electron transfer flavoprotein subunit P38117 R beta 24.27 4 O.OO || 3 || 42227.8 Transmembrane emp24 domain PAS755 R containing protein 0 24.23 6 3.29 || 4 92925. Aspartate aminotransferase, P0505 R mitochondria 24.18 26 105 || 4 || 32O494, CO2880 R DNA topoisomerase 2-beta 24.04 16 C.75 4 28249.4 OF5694 R Nuclear pore complex protein Nup155 23.92 4 OOO || 3 || 291OO.9 Transmembrane emp24 domain Q93WK6 R containing protein 9 23.90 3 O.06 || 3 || 86,395.8 insulin-like growth factor 2 mRNA O00425 R binding protein 3 23.89 14 8.86 || 4 || OS 15.3 O75367 R Core histone macro-2A. 23.88 36 20 || 4. 59992 Zinc phosphodiesterase ELAC protein Q952 R 2 23.87 6 8.00 || 3 93.96.7 C6NO3 R Putative histone H2B type 2-C 23.82 O 2.89 || 4 || 248973.3 C9HAW7 R GrpE protein honolog 1 mitochondrial 23.63 1O 51 || 4 || 286OO. P14314. R Glucosidase 2 subunit beta 23.59 8 G.33 || 4 || 238O. Transcription intermediary factor 1 3263 R beta 23.54 || 36 0.50 || 4 || 136598.6 Ribosomal RNA processing protein 1 Q4884 R homolog B 23.47 4. 8.00 || 4 365067 Q01518 R Adenyly Cyclase-associated protein 2346 || 48 0.68 || 4 || 70.023.7 C5019 R Septin-2 23.42 4. O.OO 3 536236 Q10567 R AP-1 complex subunit beta- 23.3 2 .33 || 4 2497.5 6300 R AP-2 complex subunit beta 23.3 6 0.49 || 4 O. p27818 R Microtubule-associated protein 4 23.30 9 09 || 4 69092.5 P329 R Peroxiredoxin-2 23.26 4 COO || 4 || 676179 Patent Application Publication Jul. 6, 2017. Sheet 26 of 141 US 2017/0192012 A1

FEG. 6 (cont'd) Eukaryotic translation initiation factor 3 O5371 R subunit D 22.88 3 O.3 4 50994.7 Ubiquitin-like modifier-activating AAW R enzyme 8 22.8 0 2.03 4 13955.7 P43246 R DNA misnatch repair protein Msh2 22.73 A O.OO | A 25536.5 O43852 R Califieri 22.65 185 O.2 A. 48246.5 Q8AA3 R Proteasome subunit alpha type-7-like 22.47 8 0.00 3 424. A Coiled-coi-helix-coiled-coil-helix domain-containing protein 3, C9RX63 R mitochondrial 22.29 6 O.30 4 5979.9 Sarcoplasmic/endoplasmic reticulum O14983 R Calciuri APase 22.285 8 1.73 4. 2O642 C9KX7 R Nuclear pore complex protein Nup50 22.22 A. O.OO 4 38290.0 O75223 R Gamma-glutamylcyclotransferase 22.17 4. O.30 3 37086.9 C4980 R Nuclear mitotic apparatus protein 1 21.95 18 O.7 4 4855A. 11388 R DNA topoisomerase 2-alpha 21.85 32 0.29 4 24898 Woltage-dependent anion-selective P45888 R channel protein 2 2.71 18 O.24 4 O5977.8 O9WA2 R Septin-1 2.60 A O,OO 4. 62488.3 P84085 R ADP-ribosylation factor 5 239 A. 14 3 OO p18085 R ADP-ribosylation factor 4 239 4. 114 3 O. C04917 R 4-3-3 protein eta 229 12 4.03 || 4 || 31680.7 Q92769 R Histone deacetylase 2 21.25 8 90 3 17270. Heterogeneous nuclear O60812 R Fibonucleoprotein C-like 21.08 18 18 4 788.33.7 P50454. R Serpin H1 2O6 1 O53 4 155316 Q16352 R Alpha-internexin 21.05 4. O49 3 0.0 inosine-5'-monophosphate 12268 R dehydrogenase 2 2.04 6 26 A 98.266.8 Vesicle-associated membrane protein O95292 R associated protein BC 2O3 a 2,08 4 OO265.3 CO2543 R 60S ribosomal protein 8a 2O3 14 68 4 30208.9 O6737 R Glycogen phosphorylase, Siver form 2O.79 2 2.46 4 688044 35221 R Catenin alpha-1 20.79 8 O.26 4. 2187.2 Peptidyl-prolyi cis-trans isomerase A A2BFH1 R like 4G 20.76 6 08 A. 8. Peptidyl-prolyi cis-trans somerase A F5H284 R ke 4) 20.76 6 1.08 4 O.O 93UF5 R Tousin beta-6 chair 20.76 1 77 4 730140 P352. R Radixi 20.4 4 O.00 4. 77.5674 Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, p1399.5 R mitochondrial 20.38 6 O.9 4 30983.8 8NF4. R Putative protein FAM10A5 2O2 8 0.86 4. 8. Patent Application Publication Jul. 6, 2017. Sheet 27 of 141 US 2017/0192012 A1

FIG. 16 (cont'd) Patelet-activating factor P43034. R acetylhydrolase B subunit alpha 20.9 3 18 4 95643 CO8203 R Amidophosphoribosyltransferase 20. 9 6 8.4 3 536O4.7 P35637 R RNA-binding protein FUS 2008 46 3.05 4 21943.6 Protein-L-isoaspartate(D-aspartate) O P22061 R methyltransferase 2O.OO 4. COO 3 92927.9 Serine/threonine-protein phosphatase P36873 R PP1-gamma catalytic subunit 19.8O 4 COO 3 O.O. Serine/threonine-protein phosphatase ps236 R PP1-alpha catalytic subunit 1980 4. O.OO 3 36688.7 P629.17 R 60S ribosomal protein L8 19.8 O || 0.74 4 322312.3 p50502 R Hsc70-interacting protein 1968 18 || 2 || 4 || 2075.06.0 CO2952 R A-kinase anchor protein 12 1957 6 0.00 4. 2654.30 (3ZCM7 R Tubulin beta-8 chain 1942 3 S.OO || 3 || 48526. A P227 R Nucleoprotein TPR 9.42 13 5.84 A 54336.5 82P2 R Putative protein FAMOA4 9.27 10 | 89 A 33689.C. O5459 R Splicing actor 3A subunit 1 9.21 4. 162 4 1907210 P2525 R DNA replication licensing factor MCM3 9.4 O || 2.24 4 154778.4 pO8758 R Annexin A5 18.99 12 || 3.42 4 218430,4 P55786 R Puromycin-sensitive aminopeptidase 8.93 3 88 4 75752.2 P25786 R Proteasome subunit alpha type-1 8.8O 4. 8.00 3 41697.7 Q0780 R Exosome component 10 1878 8 || 8.53 4 32681 3547 R Histone deacetylase 1 18.75 6 3.42 3 21522.7 Q9NR3G R Nucleolar RNA helicase 2 8.73 16 || 3:09 A 53.386.1 P49589 R Cysteine-trNA ligase, cytoplasmic 13.70 22 | 68 4 18351.0 CR00341 R Vigin 18.25 A 0.00 4. 51680.9 P49792 R E3 SUMO-protein ligase RanBP2 18.23 6 66 4 O9366 !Nascent polypeptide-associated C13765 R complex subunit alpha 8.2O 8 0.43 || 3 || 2:38:27.6 Probable global transcription activator p2837. R SNF2 18.08 A | COO 3 884.7 27348 R 14-3-3 protein theta 1786 4 || 2.78 4 366307.9 PA5973 R Chronobox protein honolog 5 1783 14 || 39 || 4 || 4099.52.9 Zinc finger CCCH domain-containing C8,90 R protein 5 17.72 8 C.88 4 87.507.3 C1549 R Pecti 17.70 18 COO A 128S Eukaryotic translation initiation factor A CO483 R ganna 1748 O 8.00 3 482.8 C75533 R Splicing factor 3B subunit 1 740 9 5.57 4 16903.1 P3063 R Pyruvate kinase PKLR 7.05 16 58 4 O.O. Aminoacyl tRNA synthase complex O 3155 R interacting mutifunctional protein 2 6.95 8 1.93 4 O5726.6 Patent Application Publication Jul. 6, 2017. Sheet 28 of 141 US 2017/0192012 A1

FIG. 16 (cont'd) Guanine nucleotide-binding protein-like Q9BWP2 R 3. 16.71 2 23 4 9698.7 28838 R Cytosol aminopeptidase 1658 4. O.OO 4 25589.6 Zinc finger CCHC domain-containing Q6NZY4 || R protein 8 16.58 A. O.00 3 22398.9 ATA-binding protein-associated factor 928.04 R 2N S.40 28 0.59 4. 99.345.0 P23284. R Peptidyl-proly cis-trans isomerase B 640 4 102 a 4377.7 P552O3 R Nucleosome assembly protein 1-like 18.6 8 350 a 45759.8 Q9HOAO | R N-acetyltransferase 10 16.14 8 6.77 4 66469.0 26S proteasome non-ATPase P55036 R regulatory subunit 4 15.90 4 O.00 3 9824.1 P31947 R 4-3-3 protein sigma 1586 2 2.6 3 O.O O14566 R DNA replication licensing factor MCM6 5.80 5 3.44 A 77087.0 C15293 R Reticulocabin- 5.72 22 0.99 A 33219.6 PO7205 R Phosphoglycerate kinase 2 15.57 4 30 A O.O 2236 R ADPATP transiocase 3 15.46 O 459 a 17578. P78347 R General transcription factor - 1528 80 O.86 A 3.1632.8 Q965 R Serineithreonine-protein kinase SMG 15.15 8 O.OO 3 O.O O8ECU4 R Alstrora syndrome protein 15.11 6 O.OC 4. O.O O14008 R Cytoskeleton-associated protein 5 14.75 6 O. 4 2O84. P23526 R Adenosylhomocysteinase 14.43 AO 98 || 4 || 733O8. P6949 R Stathin 13.74. 2 0.34 || 3 || 392.0 O93045 R Stathin-2 13.74. 2 0.34 3 78.355.1 P35579 R Myosin-9 13.58 6O 2.75 A 39.1814 O9211 R Gathione S-transferase P 13.53 4. 5.57 A 1723.4 Q86.JP2 R Kinectin 13.43 48 188 A 6232.8 Tyrosine-protein phosphatase non CO6124 R receptor type 1 13.7 12 2.04 3 5663O4. P2235 R ADPAP transiocase 1 13.02 6 5.44 4. 139895 Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, 10515 R nitochondria 12.78 3 A63 a 33684.5 Q8WF4. R Dyein heavy chain 10, axonema 12.45 4. 2 A 8.0 OOO59 R Unconventional myosin-ic 12.44 8 O.OO 3 42.5 Structural maintenance of O95347 R chromosomes protein 2 12.30 16 17 4. 74568.5 O15637 R Spicing factor 10.82 4 OOO 3 1189.5 PA9588 R Alanine-tRNA ligase, cytoplasmic 10.43 22 AO | A 17944.7 C16891 R Mitochondria inner membrane protein 1OOO AO 2.56 a 16733.9 PS2833 R Cellular nucleic acid-binding protein 9.95 O2 O.75 4. 53399.5 Patent Application Publication Jul. 6, 2017. Sheet 29 of 141 US 2017/0192012 A1

FIG. 6 (cont'd) NADH-ubiquinone oxidoreductase 75 P2833 R ka subunit, mitochondria 9.83 10 || 0.08 || 3 237.3 CR 13428 R 9.43 58 || 0.5 || 4 23529.4 UDP-glucose:glycoprotein Q9NY 2 R glucosyltransferase 1 9.38 4 || OOO || 3 || 13893.9 Q8WWN7 R Ataxin-2-like protein 924 28 || 09 || 4 3648.2 PA6779 R 60S ribosonal protein L28 843 12 || 0.49 || 3 || 4844 Cuir-associated NEOD8-dissociated Q86WPS R protein 3.34. 16 || 2.95 || A. 390483 CR5 W289 R DENN domain-containing protein 4C 8.18 4. OOO 3 O. P35659 R Protein EK 813 3 | 1.75 || 3 || 3555.0 norganic pyrophosphatase 2, C9H22 R ritochondria: 739 28 0.60 || 4 || 74278.8 Neuroblast differentiation-associated CRO9666 R protein AHNAK 7.17 6 106 || 4 803340 Eukaryotic translation initiation factor 3 P55884 R Sbut B 573 4 || O.80 || 4 || 8986.9 Q9YAG6 R Tan-2 570 8 2.4 || 4 O.O C9NSE4 R soleucine-tRNA ligase, mitochondrial 5.6 16 || 3.32 a 210777.8 Dolichyl-diphosphooligosaccharide PO4843 R protein glycosyltransferase subunit 1 5.49 3 || 48 || 4 || 9,490.7

C14686 R histone-ysine N-methyltransferase 2D 5.48 8 150 3 O.O. P698 R 14-3-3 protein gamma 5.42 18 2.88 || 4 || 153996.8 C621 R Uncharacterized protein C11orf57 528 6 0.00 3 O.0 p56537 R Eukaryotic trafnslation initiation factor 6 1000.00 10 0.00 || 4 || 50492.0 Dolichyl-diphosphooligosaccharide protein glycosyltransferase 48 kDa P39656 R subunit 1000.00 A O,OO || 4 || 140039 Eukaryotic translation initiation factor PO6730 R 4E OOOOO 18 || 0.80 || 3 107713 C7Z334 R p54 1008.00 18 || 0.80 || 3 15875.5 POO387 R NADH-cytochrone b5 reductase 3 1000.00 16 || 000 || 3 || 48586.3 CR9NZW5 R MAGUK p55 subfamily member 6 1OOOOO 9 O.OO || 3 || O6589.0 831.87 R Dynein light chain , cytoplasmic 1OOOOO | 8 || O.OO || 3 || 21276.8 (13363 R C-terminal-binding protein 1OOOOO 8 OOO 3 51279 Eukaryotic translation initiation factor 3 C7582 R subunit G 000.00 || 8 || O,OO || 3 || 8807.0 Eukaryotic translation initiation factor O4602 R A Y-chromosoma OOOOO 3 0.00 || 3 || 42347.4 Cytoplasmic dynein 1 light C9Y6G9 R intermediate chain 1OOOOO 7 O.00 || 3 23983.8 Q9Y263 R Phospholipase A-2-activating protein OOOOO 6 OOO || 3 5759.7 Patent Application Publication Jul. 6, 2017. Sheet 30 of 141 US 2017/0192012 A1

FIG. 16 (cont'd) Putative eukaryotic translation initiation Q2WR3 R factor 2 subunit 3-like protein 1OOOOO 4 OOO 3 1078.3 P62269 R 40S ribosomal protein S18 O0800 3 OOO 3 5248.0 39S ribosomal protein L46, C9H2W6 R hitochondria: OOOOO 3 O.00 || 3 2O7698 O6060 R Protein diaphanous homolog 1OOOOO 12 || OOO || 3 24477 Eukaryotic transiation initiation factor C9EY44. R 2A 1000.OO 10 || 000 || 3 1240.O C8AF3 R WD repeat-containing protein 48 OOOOO || 9 || 000 || 3 O.O. C13098 R COP9 signatosome complex subunit 1 || 1000.00 || 6 O.OO || 3 330.9 CR9NR22 R Protein arginine N-methyltransferase 8 || 1000.00 || 6 0.00 || 3 O.0 CB75663 R TP41-like protein 1000.00 || 5 || OOO || 3 29.188.8 C32A3 R Serinelarginine-rich splicing factor 5 1000.00 || 5 || 000 || 3 57586 Electron transfer flavoprotein ubiquinone oxidoreductase, C1634. R nitochondria: 1OOOOO 5 OOO || 3 O.O. Cytosolic acyl coenzyme A thioester COO154 R hydrolase OOOOO A OOO 3 5025.2 26S proteasome non-APase OBO487 R regulatory subunit 4 1OOOOO 4 OOC 3 O.O. U4/U6 sma: nucleaf ribonucleoprotein O4372 R Pro4 1OOOOO 4. OOO 3 2648.4 O954. R Splicing factor, arginine?serine-rich 15 000.00 4 O.00 || 3 22632O isocitrate dehydrogenase NAD P5023 R subunit alpha, mitochondrial 1000.00 || 4 || O,OO || 3 || 4848.9 NEDD8-activating enzyme E1 catalytic Q83C4 R subunit OOOOO 4. OOO || 3 || 2632.3 Q9996 R Endophilin-A2 OOOOO 4 O.OO 3 53180.3 Choline-phosphate cytidylyltransferase O9Y53 R B OOOOO a OOO 3 141984 O14744 R Protein arginine N-methyltransferase 5 || 1000.00 3 O.OO 3 2317.2 P5500 R Eukaryotic translation initiation factor S 1000.00 || 3 || 0-00 || 3 | 40970.1 DnaJ homolog subfamily A member 3, C96EY R itochodria: 1OOOOO 3 0.00 3 A920.2 J3 small nucleolar RNA-associated C9E3WS R protein 14 homolog A OOOOO 3 O.00 || 3 1079.2 Q9Y3A5 R Ribosome naturation protein SBDS OOOOO 3 0.03 || 3 7292.9 Acyl-CoA synthetase short-chain C96R3 R family member 3, mitochondrial 1OOOOO 10 OOO 3 O.O. P4O938 R Replication factor C subunit 3 1OOOOO 7 O.OO 3 893.9 Glucose-6-phosphate 1 P 143 R dehydrogenase 1OOOOO 6 OOO || 3 3482.7 RNA-binding motif, single-stranded P29558 R interacting protein 000.00 || 4 || 000 || 3 5074.0 Patent Application Publication Jul. 6, 2017. Sheet 31 of 141 US 2017/0192012 A1

FIG. 16 (cont'd) Eukaryotic translation initiation factor 3 75822 R subunity OOOOO || 3 || OOO 3 6250. Serine?threonine-protein phosphatase Q6N85 R 4 regulatory subunit 3A OOOOO || 8 || O.OO 3 O.O. CSUB2 F SUMO-activating enzyme subunit 2 1OOOOO 103 OOO | 4 || 854.73.8 17858 r 6-phosphofructokinase, liver type OOO.OO 98 O.OO 4 72902.3 Replication protein. A 70 kDa DNA 27694 r binding subunit OOOOO | 73 8.00 || 4 || 70226.6 C8AFSO PHD finger protein 6 OOOOO | 68 0.00 4 2968.2 Of 513 r Copine-3 OOOOO || 62 8.00 4 97047.3 1592 F Replication protein. A 32 kDa subunit OOOO 57 O.O. 4. 4998.4 RNA polymerase-associated protein C9254 t RTF1 homolog 1OOOOO 50 .00 4 16702.6 61158 t Actin-related protein 3 OOOOO || 43 O.00 4 7292.4 Ribosome biogenesis regulatory C15050 r protein honolog OOOOO || 42 8.00 || 4 || 110229.2 C9H984 F Sideroflexin- OOOOO | 40 8.00 || 4 || 110598.9 U3 smal nucleolar ribonucleoprotein O00568 protein MPPO OOOOO || 36 O.OO A 2A573.4 C8NN5 F 60S acidic ribosomal protein P0-like OOOOO 28 O.OO 4 || 135224.9 Leucine zipper transcription factor-ike Q9NQ48 F protein OOOOO || 28 0.00 a || 381573 Q9Y224 r UPF0568 protein C14orf166 OOOOO || 25 O.OO || 4 || 1244,089 socitrate dehydrogenase NADP, P48738 ritochondria OOOOO 23 8.OO | 4 || 1:44.85.1 C1688 Proteasoma ubiquitin receptor ADRM | 1000.00 || 14 0.00 4 38102.9 P3693 ranslationaly-controlled tumor protein 1000.00 || 3 || 0.00 4 || 12323.8 Basic leucine zipper and W2 domain SYSE2 F containing protein 2 OOOOO 10 COO 4 544052 586 F RNA-binding protein 26 1OOO.OO 192 COO 4 5138.0 Calciumical modulin-dependent protein Q13557 kinase type subunit delta OOOOO | 160 0.00 A 6577.6 26S proteasome non-ATPase OOO231 regulatory subunit 1 OOOOO 12 8.00 4. 4403.9 98WF3 F RNA-binding protein 4 OOOOO || 100 8.00 4 14393.7 PA3444 Coatomer subunit delta OOOOO 95 O.OO 4 17257.5 Puromycin-sensitive aminopeptidase ASNEC2 F like protein OOOOO | 84 0.00 4 O. p5774 Nuclear pore complex protein Nup107 || 000.00 || 82 0.00 4 13318.O P51858 Hepatoma-derived growth factor 1OOOOO || 8 | COO | 4 || 1 3154.1 1414. r Septin-6 OOOOO | 68 COO 4 930.6 P82191 26S protease regulatory subunit 4 OOOOO | S7 O.00 || 4 || 2434594. P28074 r Proteasome subunit beta type-5 OOOOO || 58 O.OO 4 19397.7 Patent Application Publication Jul. 6, 2017. Sheet 32 of 141 US 2017/0192012 A1

FIG. 6 (cont'd)

P28066 F Proteasome subunit alpha type-5 1OOOOO 44 O.OO 4 28135.6 P22087 F rRNA 2'-O-methyltransferase fibrillarin 1000.00 43 0.00 || 4 || 215023.1 O9BOO4 F RNA-binding protein 4B 1OOOOO 38 O.OO 4 10646.5 CR9Y696 Chloride intracellular channel protein 4 || 1000.00 38 0.00 || 4 || 205678.9 CR9HB71 r Calcyclin-binding protein 1OOOOO 37 O.OO 4 85949.3 CR 13596 Sorting nexin-1 OOOOO 36 O.OO 4 2560.7 C9HOU4 F Ras-related protein Rab-1B OOOOO 22 O,OO 4 11014.6 OR 14696 LDLR chaperone MESD 1OOOOO 21 O.OO 4 33760.4 PO9234 U1 small nuclear ribonucleoprotein C 1OOOOO 9 O.OO 4 89629.5 Peptidyl-prolyl cis-trans isomerase C13526 r NIMA-interacting 1 1OOOOO 5 O.OO 4 || 178903.8 Q12959 r Disks large homolog 1 1OOOOO 395 O.OO 4 367O1 POO390 Glutathione reductase, mitochondrial 1OOOOO 221 O.OO 4 1759.2 Calcium-binding mitochondrial carrier Q9JJSO F protein Aralar2 1OOOOO 162 O.OO 4 19068.O CR 14444 r Caprin-1 1OOOOO 95 O.OO 4 1943.38 Pyruvate dehydrogenase phosphatase O8NCN5 regulatory subunit, mitochondrial 1OOOOO 82 O.OO 4 25371.9 Q52LJO F Protein FAM98B 1OOOOO 79 O.OO 4 206019 P23396 F 40S ribosomal protein S3 1OOOOO 69 O.OO 4 128590.6 O43684 F Mitotic checkpoint protein BUB3 1OOOOO 51 O.OO 4 29O15.3 P61160 F Actin-related protein 2 1OOOOO 48 OOO 4 19530.8 C9Y5S9 F RNA-binding protein 8A 1OOOOO 43 O.OO 4 40888.4 O75947 ATP synthase subunit d, mitochondrial 1000.00 38 0.00 4 16782.1 CRO8752 r Peptidyl-prolyl cis-trans isomerase D 1OOOOO 26 OOO 4 2859.5 Regulation of nuclear pre-mRNA Q9MQG5 F domain-containing protein 1B 1OOOOO 18 OOO 4 35486.7 POO568 Adenylate kinase isoenzyme 1 OOOOO 16 O.OO 4 37598.4 sovaleryl-CoA dehydrogenase, P26440 mitochondria 1OOOOO 15 O.OO 3 22893.6 CR3MHD2 F Protein LSM12 homolog 1OOOOO 14 OOO 4 691847 Ribose-phosphate pyrophosphokinase P21108 3 1OOOOO 5 O.OO 4 O.O CR9Y450 HBS1-like protein OOOOO 12O OOO 4 82262 Cell division cycle and apoptosis O8X12 regulator protein 1 1OOOOO 108 O.OO 4 5699.3 P33991 r DNA replication licensing factor MCM4 1000.00 96 || 0.00 || 4 57897.2 Vacuolar protein sorting-associated Q96OK1 F protein 35 1OOOOO 78 O.OO 4 3O155.4 Ornithine aminotransferase, PO4181 F mitochondrial 1OOOOO 68 O.OO 4 173914 PO6493 Cyclin-dependent kinase 1 OOOOO 57 O.OO 4 60375.1 Patent Application Publication Jul. 6, 2017 Sheet 33 Of 141 US 2017/O192012 A1

FIG. 16 (cont'd) NADH dehydrogenase ubiquinone P49821 flavoprotein 1, mitochondrial 1OOOOO || 44 OOO 4 8924.9 P22059 Oxysterol-binding protein 1 1OOOOO || 41 O.OO 4 O.O Phenylalanine--tRNA ligase alpha Q9Y285 F Subunit 1OOOOO || 37 O.OO 4 832O.O OOO186 F Syntaxin-binding protein 3 1OOO.OO || 34 O.OO 4 32924.2 O9BWS9 F Chitinase domain-containing protein 1 1000.00 28 0.00 3 O.O O99986 F Serine/threonine-protein kinase VRK1 1OOOOO || 25 OOO 4 188414 ATP-dependent RNA helicase O8YB8 SUPV3L1, mitochondrial 1OOO.OO 24 O.OO 4 O.O P62263 40S ribosomal protein S14 1OOOOO | 19 O.OO 4 91546.8 Small glutamine-rich tetratricopeptide O43765 repeat-containing protein alpha 1OOOOO | 18 OOO 4 25256.3 P58546 Myotrophin 1OOOOO || 4 OOO 4 691.82.3 P29692 Elongation factor 1-delta 1OOOOO | 183 O.OO 4 76522.3 Cytoplasmic dynein 1 intermediate Q13409 F chain 2 1OOOOO | 168 O.OO 4 14857.6 Asparagine synthetase glutamine PO8243 hydrolyzing 1OOO.OO 140 O.OO 4 3930.8 O12765 Secernin-1 1OOOOO | 137 O.OO 4 12312.8 P26232 Catenin alpha-2 1OOO.OO | 130 O.OO 4 O.O Far upstream element-binding protein O9624 3 1OOOOO | 112 O.OO 4 51414.4 O60828 Polyglutamine-binding protein 1 1OOOOO | 104 O.OO 4 321842 DNA fragmentation factor subunit OOO273 F alpha 1OOOOO 96 O.OO 4 20267.O Chromodomain-helicase-DNA-binding O86WJ1 F protein 1-like 1OOOOO 96 O.OO 4 1303.0 Suppressor of G2 allele of SKP1 Q9Y2ZO homolog 1OOO.OO || 76 O.OO 4 2405.9 CR9UJU6 Drebrin-like protein 1OOOOO || 75 O.OO 4 O.O Hepatoma-derived growth factor O7Z4V5 related protein 2 1OOOOO | 73 O.OO 4 3O37O.O O9Y5A7 NEDD8 ultimate buster 1 1OOO.OO | 73 O.OO 4 8371.6 O9UPN9 F E3 ubiquitin-protein ligase TRIM33 1OOOOO || 71 O.OO 4 OO Hepatocyte growth factor-regulated O 14964 tyrosine kinase substrate 1OOOOO || 70 O.OO 4 22365.0 O8NEY8 Periphilin-1 1OOOOO | 68 O.OO 4 O.O Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta O 14738 F isoform 1OOO.OO | 66 O.OO 4 O.O O96ST3 F Paired amphipathic helix protein Sin3a 1000.00 | 66 0.00 4 9528.4 O60664 F Perilipin-3 1OOOOO | 62 O.OO 4 14738.O O96017 F Serine/threonine-protein kinase Chk2 1OOOOO || 59 OOO 4 5272.9 Patent Application Publication Jul. 6, 2017. Sheet 34 of 141 US 2017/0192012 A1

FIG, 16 (cont'd) P25440 Brosnodomain-containing protein 2 OOOOO 58 8.0 4 O C9NCX3 F Gephyri? 1800.00 || 56 800 || 4. O.O Q14677 Clathin interactor 1300.OO || 5A 300 || 4. OO C9ROR6 F Dynamin-3 18OOOO 52 OOO 4 0.0 C86 E4 F Protein YRC 1000.OO | A7 000 || A. 14 O.2 Ubiquitin-conjugating enzyme E2 O3404 variant OOOOO 45 OOO 3 3:63 Probable ATP-dependent RNA Q9NCEO r helicase DOX4 1OOOOO || 45 0.08 || 4 G.O O9YAW6 F AFG3-like protein 2 1OOOOO 45 OOO 3 19356 Q98Y77 r Polymerase delta-interacting protein 3 1000.00 43 0.00 4 15675.4 O9839 F Tuftelin-interacting protein 1000.00 || 43 O.OO || 4 O.O P25788 Proteasone subunit alpha type-3 OOOOO || 42 O.OO || 3 0.0 P83208 r S-phase kinase-associated protein 1800.00 || 4 || 3:00 || 4 SO343 U3 saucleolar RNA-associated Q8EO protein 15 homolog 1OOOOO || 38 O.OO | A. 0.0 O99541 r Perilipin-2 1000.00 || 35 O.OO || 4. 62828.0 O9NY 9 F roponodulin-3 OOOOO 32 O.OO || 4 || 25381.8 P4240 c Tyrosine-protein kinase CSK OOOOO || 3 || O.OO 4. 86745 Myristoylated alanine-rich C-kinase P29966 F substrate 1000.OO || 28 0.08 || 4 || 4099.6 C96ME7 F Zinc finger protein 512 1OOOOO || 28 0.08 || 4 7243.7 Vacuolar protein sorting-associated O9-269 F protein 16 homolog OOOOO 28 8,00 4 O.O Q9NP3 Acyl-coenzyme A thioesterase 13 1000.OO 28 000 || 4 O.O Membrane-associated progesterone OOO264 receptor component 1 1OOOOO 27 OOO 4 84932.9 P6326 Protein mago nashi honolog OOO.OO || 26 800 || 4. 780.4 O60508 Pre-mRNA-processing factor 17 1OOOOO || 25 000 || 4 0.0 BAG family molecular chaperone O9587 regulator 3 OOOOO 25 O.OC 4. 774.842 iDelta(3,5)-Delta(2,4)-dienoyl-CoA C13011 isomerase, mitochondria 1OOOOO 25 OOO 4 133775.8 O8WWK9 F Cytoskeletor-associated protein 2 100D.OO 25 O.OO 4. O S-adenosylmethionine synthase P3153 isoform type-2 1OOOOO || 24 0.00 || 4 4,6962.8 P47755 F-actin-capping protein subunit alpha-2 1000.00 24 0.00 4 8042.6 Pre-rrNA-processing protein TSR1 CR2N82 F honolog 100.00 2A 000 || 4 43O29.7 C9EW2 F Protein sel-1 homolog 1 1OOOOO || 24 000 || 4 0.0 QOO796 Sorbitol dehydrogenase 1OOOOO || 23 0.08 || 4 17053.8 CR9NRX4 F 14 kDa phosphohistidine phosphatase 1000.00 || 23 0.00 || 4 88524.8 Patent Application Publication Jul. 6, 2017. Sheet 35 of 141 US 2017/0192012 A1

FIG. 6 (cont'd) SAP domain-containing P82979 ribonucleoprotein OOOOO 22 O.OO 4. OO Eukaryotic translation initiation factor 3 Q72H7 F Subunit M OOOOO 22 OOO 4 857954 ransmembrane emp24 domain O7Z7H5 F containing protein 4 OOOOO 22 0.00 4 OO P62888 60S ribosomal protein 30 OOOOO 21 0.00 4 4O7262.O. Very-long-chain (3R)-3-hydroxyacyl CR9035 acyl-carrier protein dehydratase 3 OOOOO 21 O.00 4 64256.3 O969W3 Nicai OOOOO 2O 0.00 3 OO L-2-hydroxyglutarate dehydrogenase, Q99P8 F mitochondria OOOOO 20 O.OO 4 OO O563 raisin OOOOO || 8 || 000 4 928663 C13888 F Exosome complex component RRP4 1 OOOOO || 7 || O.OO A. CO O92820 Gamma-glutamy hydrolase OOOOO || 7 || O.00 4 46993 Cytochrome b-C complex subunit P47985 Rieske, mitochondria 1 OOOOO || 5 || 0-0 || 4 || 17839.4 C3685 r Angio-associated migratory cel protein 1000.00 5 0.00 4 15690.4. C9NZZ3 Charged nutivesicular body protein 5 || 000.00 || 5 || 0.00 4 30556 O80493 r Sorting nexin-3 1OOOOO || 4 || O.OO 4 573.3 Peptidyl-prolyi cis-trans isomerase P6294.2 FKBP1A OOOOO || 4 || O.OO 4 96532.1 Methylthioribulose-1-phosphate C96GX9 F dehydratase 1OOOOO || 4 || O.OO 3 9436. Cancer-feated nucleoside O9BSf F triphosphatase OOOOO 4 0.00 4 OO Histidine triad nucleotide-binding O98X68 protein 2, mitochondrial OOOOO || 4 || 0.00 4 48506,1 PS238 f Snai nuclear ribonucleoprotein Sn D3 1000.00 || 2 || 0.00 || 4 || 1404.8 Q1547 Caponin-3 OOOOO 2 OOO 4 70468.0 Eukaryotic translation initiation factor 3 Q9 BCR5 F subunit K OOOOO 12 O.OO 4 88968 P49643 DNA prinase large subunit 1000.OO O.08 4 3097.6 C99598 Transin-associated protein X OOOOO 31 O.OO 4 70813. C9782 Ribosome production factor 2 homolog 000.00 1 0.00 4 63620 RNA-binding protein Musashi homolog O4334.7 1 OOOOO || 0 || O.OO 3 OO P62277 40S ribosomal protein S3 OOOOO O OOO 4 5.840.6 Q9MYA F Sorting nexin-12 1OOOOO O O.OO 4 1563,5 P05387 60S acidic ribosomal protein P2 OOOOO 9 OOO 4 O.O. 39S ribosomal protein 12, P52815 mitochondria OOOOO 9 OOO 4 33450,7 P62857 40S ribosoma protein S28 1000.OO 9 O.OO 4 90.972.7 C8N383 Mimitin, mitochondrial OOOOO 9 OOO 3 6424.0 Patent Application Publication Jul. 6, 2017. Sheet 36 of 141 US 2017/0192012 A1

FIG. 6 (cont'd) ATP synthase mitochondrial F1 Q8N5M1 F complex assembly factor 2 1000.00 9 O.OO 4 O.O Regulator of microtubule dynamics Q96DB5 F protein 1OOOOO || 9 || OOO 4 10557.3 Guanine nucleotide-binding protein C9HAVO F Subunit beta-4 1000.00 || 9 || O.00 4 80 Endotheta differentiation-related O8O869 f factor 1000.OO || 8 || O.OO 4 25550.8 Glycylpeptide N O6055 F tetradecanoyltransferase 2 1080.30 7 || O.30 4 58066.3 RNA-binding motif protein, X-linked O755.26 r like-2 10O.OO 7 OOO 3 O O969R2 Oxysterol-binding protein 2 1OOO.OO 7 OO a 8. P82745 F Rho-related GTP-binding protein Rhos 1000.00 || 4 || 0.00 4 0, KH domain-containing, RNA-binding, signal transduction-associated protein Q5WWX F 2 108O.OO 4 0.30 4 OO Q9NR56 F Muscleblind-like protein 10O.OO 108 || OOO 3 13760.6 O60701 F UDP-glucose 6-dehydrogenase 1000.00 98 || 0.00 3 3004.2 Heterochromatin protein 1-binding Q5SS5 F protein 3 180.3O 85 || OOO 3 11585.4 28S ribosomat protein S29, P5398 F mitochondria 1000.00 || 8 || 0.00 3 0.0 P3591 r Neural Ce adhesion inolecule 1OOOOO 80 || OOO 3 80 Histone-arginine methyltransferase C86X55 F CARM 108O.OO 70 || OOO 3 60974 Serine/threonine-protein kinase MRCK Q5WT25 F alpha 1000.00 66 O.80 3 O.O O4126 Desmogiein-2 100O.OO 65 || OOO 3 25585.1 Kinetochore-associated protein DSN1 C9H4O F homolog 1000.00 64 0.00 3 OO O95782 AP-2 complex subunit alpha-1 1OOO.OO 58 O.30 3 O.O. Epidermal growth factor feceptor PA2566 r substrate 15 1OOOOO 56 || O.OO 3 43752 Myosin phosphatase Rho-interacting Q8WCCR1 F protein 1OOO.OO || 5 || OOO 3 80 C96G74 F OT domain-containing protein 5 1000.00 46 O.OO 3 O O8Z21 F Phosphatase and actin regulator 4 1OOO.OO 42 O.OO 3 3.0 C93 WA F COOni-C 1000.OO 39 || OOO 3 40340 inosine-5'-monophosphate P2O839 F dehydrogenase 1 1000.00 32 O.80 3 O.O Zinc finger FYVE domain-containing Q7Z3T8 r protein 16 1OOOOO 32 || O.OO 3 OO hematological and neurological C9H90 F expressed 1-like protein 1000.OO 30 || O.OO 3 43644.7 Patent Application Publication Jul. 6, 2017. Sheet 37 of 141 US 2017/0192012 A1

FIG. 16 (cont'd) Ras GTPase-activating protein-binding C9UN88 F protein 2 100.00 || 3 || OOO 3 SO936. Serine/threonine-protein kinase MRCK QSY5S2 beta 1000.00 30 O.OC 3 O.O. Soluble lamin-associated protein of 75 C9Y6X4 F ka 1000.00 29 || O.OO 3 O.O Enoyl-CoA delta isomerase 1, PA226 nitochondria OOOOO 28 OOO 3 6751.3 Arf-GAP domain and FG repeat P52594 F containing protein 1000.00 28 || O.00 3 O.O. Cat eye syndrome critical region C93XW7 F protein 5 OOOOO 28 || OOC 3 8455.8 C9EE9 F Craniofacial development protein 1000, 27 0.08 3 17859.3 O75528 r Transcriptional adapter 3 OOOOO 26 || 000 3 O.O. Prostaglandin F2 receptor negative C9P282 F regulator 10OOOO 26 0.00 3 O. GTP:AMP phosphotransferase AK3, C9U.7 nitochondria OOOOO 26 || OOC 3 O. 51572 r B-cell receptor-associated protein 31 1OOOO 25 || O.OO 3 115944 leucine-rich repeat-containing protein C9H.9A6 F 40 OOOOO 25 || O.OO 3 OO C9P2K5 Myelin expression factor 2 1OOOOO 25 || OOO 3 O.O Serie? threonine-protein phosphatase C96HSt F PGAM5, mitochondria OOOOO 23 O.OO 3 2866.2 C81 ATP-dependent RNA helicase DDX54 1000.00 22 0.00 3 O. G9NQE5 F Exosome complex component RRP40 1000.00 22 0.00 3 D.O. Q9UNN5 F FAS-associated factor COO.00 22 || OOC 3 3932.6 P9784 Casein kinase is subunit alpha OOOOO 21 || OOO 3 D.O. CR 5022 Polycomb protein SUZ12 1OOOOO 9 OOO 3 O.O. Q72739 F YTH domain family protein 3 100.0 19 O. 3 O.C. BTB/POZ domain-containing protein Q98CX2 F KCTD12 1OOOOO | 9 || OOO 3 O.O P6G888 r 40S ribosomal protein S20 1OOOOO | 8 || OOO 3 64829.3 Mitochondrial import receptor subunit O96008 TOM40 homolog OOOOO 7 OOO 3 O.O. Gutary-CoA dehydrogenase, Q92947 F mitochondrial 100COO 7 || OOO 3 1355.4 Q9NWM9 F Protein asunder homolog 1000,00 O.00 3 O.O P4681 r 40S ribosomal protein S9 OOOOO | 6 || OOO 3 24507.4 Zinc finger CCCH-type antiviral protein C96H79 1-like OOOOO | 6 || OOC 3 0269.8 39S ribosomal protein 39. Q9MYKS F mitochondria 1OOOOO | 6 || OOO 3 O.O. P6106 r Ras-related protein Rab-14 OOOOO 15 || OOO 3 O.O. Q008 F Spicing factor U2AF 35 kDa subunit 1OOOOO | 5 || O.OO 3 21028 Patent Application Publication Jul. 6, 2017. Sheet 38 of 141 US 2017/0192012 A1

FIG. 6 (cont'd) Q8NOY7 | F Probable phosphoglycerate nutase 4 1OOOOO || 5 || OOO || 3 OO Ch9NXV6 F CDKN2A-interacting protein 1000.00 || 5 || 000 || 3 O.O Q8XCR4 t GPALPP motifs-containing protein 1000.00 || 4 || O.OO || 3 235273 C9NRL3 F Striatin-4 1OOOOO | 1.4 OOO || 3 O.O. CR9 GP8 F Translocation protein SEC63 homolog 1000.00 14 0.00 3 OO Peptidyl-prolyl cis-trans isomerase-iike

CR9Y3Y2 F Chromatin target of PRM protein OOO.OO || 14 OOO || 3 9950 OOO629 F nportin subunit alpha-3 OOOOO | 13 O.CO || 3 OO P48637 r Glutathione synthetase 1000.00 || 3 || O.OO || 3 O.O Probable E3 ubiquitin-protein ligase C9HOOO F nakorin-2 100,00 || 13 O.OO || 3 38568.5 Ubiquitin carboxyl-terminal hydrolase p15374. isozyme L3 1OOOO || 2 | OOO || 3 0. 395 F Core-binding factor subunit beta 1OOO.OO | 12 O.OO || 3 O.O Mesencephalic astrocyte-derived P5545 r neurotrophic factor OOOOO || 1 || O.OO || 3 0.0 C960 THO complex subunit 3 OOOOO | 11 O.CO || 3 OO O4344.7 Peptidy-prolyl cis-trans isomerase H OOOOO || 10 O.OO || 3 73443.9 Vacuolar protein sorting-associated O75351 r protein 4B 1OOO.OO || 10 O.OO || 3 O.O RAC-alpha serine?threonine-protein P31749 r kinase OOOOO || 1 O O.OO || 3 0.0 Proteasome activator complex subunit PS 1289 r 3. 1000.00 || 1 O OOO || 3 7012.8 C96K7 Transcription factor BTF3 homolog 4 OOOOO || 10 O.OO || 3 || 5579.6 Q9BRX8 F Redox-regulatory protein FAM23A 100COO | 10 0.00 || 3 O.O MK167 FHA domain-interacting Q9BYG3 F nucleolar phosphoprotein OOOOO | 10 O.OO || 3 0.0 Ubiquinol-cytochrome-c reductase O9NWA F complex assembly factor 1000.00 || 10 OOO || 3 O.O. Ubiquitin domain-containing protein O4562 r BFD 1 1000.00 || 9 || OOO || 3 O.O PO955 f Annexin A4 1 OOOOO || 9 || OOO || 3 OO General transcription factor F subunit P13984 F 2 1000.00 || 9 || O.CO || 3 OO P4567 F Eukaryotic translation initiation factor 1000.00 || 9 || 0.00 3 O.O O96C36 || F Pyrroline-5-carboxylate reductase 2 1000.00 || 9 || OOO || 3 O,O C9E3WG4 F Protein PBOC 1000.0 || 9 || OOO || 3 9019.0 Sinai nuclear ribonucleoprotein G-like A8VWD9 F protein 100000 || 8 O.OO || 3 OO O526C t Surfeit locus protein 4 1000,00 || 8 || O.OO || 3 OO P30260 F Ce division cycle protein 27 homolog 1000.00 || 8 || 0.00 3 OO Patent Application Publication Jul. 6, 2017. Sheet 39 of 141 US 2017/0192012 A1

FIG. 16 (cont'd) 55.283 F Cadherin-4 100COO 8 OOO 3 0.0 P6 O 8 F Ras-related protein Rab-4B 10OOOO | 8 O.OO 3 OO P6234 F Small nuclear ribonucleoprotein Sm D1 1000.00 | 8 0.80 3 76033.1 p783 8 F immunoglobulin-binding protein 1 1000.00 8 0.00 || 3 992.9 Q794 F MOB kinase activator B OOOOO || 8 || 0.00 || 3 OO HLA class histocompatibility antiger, C95604 F CW-17 alpha chain 1 OOOOO | 8 OOO 3 O.O Hexaprenyldihydroxybenzoate C9NZ36 r methyltransferase, mitochondrial 100O.OO | 8 O.OO 3 OO CR9 JFN F Protein NipSnap homolog 3A OOOOO || 8 OOO || 3 OO Membrane-associated progesterone O1573 F receptor component 2 OOOOO 7 OO || 3 O.O O95336 F 6-phosphogluconolactonase OOOOO 7 0.00 || 3 31731.4 2807 Proteasone subunit beta type-4 1OOOOO 7 OOO 3 O.O. 39S ribosoma protein -1, Q93Y6 F mitochondria 1OOO.OO 7 OOO || 3 OO C9H83 F Methyltransferase-like protein 7A 1000.00 7 O.OO 3 O.O Required for meiotic nuclear division Q9NWS8 F protein 1 homolog 100COO 7 OOO || 3 OO O9NX40 F OCA domain-containing protein 1OOO.OO 7 O.OO || 3 0.0 Signal recognition particle receptor CSY5M8 F subunit beta 1000.OO 7 O,OO || 3 OO HLA class histocompatibility antiger, P 1034 F A-32 alpha chain 100COO || 6 || OO || 3 O.O HLA class I histocompatibility antigen, 1689 A-31 alpha chain 1080.OO 6 O.OO 3 OO HLA class histocompatibility antiger, 1619 A-33 alpha chain 10OOOO 6 O.OO 3 O.O HLA class I histocompatibility antiger, P8462 r A-25 alpha chain 1 OOOOO 6 OOO || 3 OO HLA class histocompatibility antiger, P30450 F A-26 alpha chain OOOOO || 6 || O.80 || 3 OO HLA class histocompatibility antiger, P30453 F A-34 apha chain 1OOOOO 6 OOO || 3 O.O HLA class I histocompatibility antigen, P3O456 r A-43 alpha chain 1080.OO || 6 || OOO || 3 OO HLA class I histocompatibility antiger, p30457 A-66 alpha chain 1000.OO 6 O.OO 3 OO HLA class histocompatibility antigen, P3O459 F A-74 apha chain OOOOO 6 OOO || 3 O.O HLA class histocompatibility antigen, 30.504 r Cw-4 alpha chain 1000.00 6 0.00 || 3 OO HLA class histocompatibility antiger, 305 2 r A-29 alpha chain 100000 || 6 O.OO || 3 O. Patent Application Publication Jul. 6, 2017. Sheet 40 of 141 US 2017/0192012 A1

FiG. 6 (cont'd) 623O8 r Smail nuclear ribonucleoprotein G OOOOO || 6 O.OO 3 OO HLA class histocompatibility antigen, Q09 160 r A-80 alpha chain 10OOOO || 6 OOO 3 O.O CR8WU68 F Spicing factor U2AF 26 kDa subunit 1OOOOO || 6 O.OO 3 OO Ubiquitin-like domain-containing CFD C8WWY7 F phosphatase 1OOOOO 6 O.OO || 3 || 52348.5 hioredoxin domain-containing protein C93RA2 F 17 1000.00 || 6 OOO 3 79898 O9BR6 F. Serinefarginine-rich spicing factor 8 OOOO || 6 OOO 3 OO Q9G2N8 F UPF0687 protein C20orf27 1OOOOO || 6 O.OO 3 OO

C9Y5W3 F Melanoma-associated antigen D 1000.OO 6 O.OO 3 O.O O75431 F Metaxin-2 OOOOO 5 O.OO 3 O.O Ribosome biogenesis protein NSA2 O95478 F homolog 1OOOOO || 5 || O.OO 3 71473.2 HLA class histocompatibility antigen, PO4222 F CW-3 alpha chain 1000.00 || 5 || O.OO 3 O.O 28338 F. Ras-related protein Rab-4A 100.00 5 0.00 3 O.O HiA class histocompatibility antigen, p30510 r CW-14 alpha chain OOOOO 5 OOO 3 OO ER membrane protein complex subunit CR 5006 F 2 1OOOOO 5 O.OO 3 OO Pateket-activating factor C15O2 acetylhydrolase B subunit gamma 1OOOOO || 5 || O.OO 3 O.O C9NOZ2 F Something about silencing protein 10 OOOOO || 5 || 0.00 3 10757.7 ER membrane protein complex subunit O434O2 F 8 18OOOO || 4 || OOO 3 O.O 98.388 F 60S ribosomal protein L36a 1000.OO 4 O.OO || 3 | 12955.3 CSXWA F Apollipoprotein O-like 1000.00 4 0.00 3 O.O 39S ribosomal protein 24, CR98A35 r mitochondria 1OOOOO 4 O.OO 3 38.93.8 C989CRO f 60S ribosomal protein 36a-like 1OOOOO 3 OOO 3 O.O Transiocon-associated protein subunit CR9N 2 F gamna OOOOO || 3 || O.OO || 3 | 89988. Acidic leucine-rich nucleaf O92688 F phosphoprotein 32 family member 8 1958 8 OOO A O.O Q3310 r Polyadenylate-binding protein 4 8.9 6 O.OO 4 79345.3 68036 r Ubiquitin-conjugating enzyme E2 L3 122.22 || 4 || OOO 3 82867.5 P8498 F 60S ribosomal protein 19 79.6 6 OOO 4 39568O.O N-alpha-acetyltransferase 15, NatA C98X9 F auxiliary subunit 69.46 4. O.OO 4 22090,8 Serinefarginine repetitive matrix Q8YB3 r protein 58.84. 8 OOO 3 64337.3 Eukaryotic peptide chain release factor 1570 F GTP-binding subunit ERF3A 53.75 8 O.OO a 50605 C4847 r LiM and SH3 domain protein 1 53.36 4 O.00 3 CO Patent Application Publication Jul. 6, 2017. Sheet 41 of 141 US 2017/O192012 A1

FIG. 6 (cont'd) Q93N22 F NSF-1 cofactor p47 50.52 6 0.00 || 4 17563.8 {962K6 F RNA-binding protein 14 49.28 18 OOO || 4 95395.1 C998.73 Protein arginine N-methyltransferase 46.7 8 O.OO | A. 62.356.O 26,368 Splicing factor U2AF 65 kDa subunit 38,41 8 0.0 || 4 20293.2 Peptidyl-prolyi cis-trans isomerase QY237 F NEMA-interacting 4 29,57 12 OOO || 4 42535.3 26S proteasone non-ATPase C43242 regulatory subunit 3 29, 18 4 0.00 || 4 || 15303.9 Q96FW Ubiquitin thioesterase OTUB 27.77 4. OOO a 1794.9 O348 f AR DNA-binding protein 43 27.06 4. OOO || 4 34,689.O C16555 r Dihydropyrimidinase-related protein 2 26,34 4. OOO 4 2O1140 Q9MK5 F Obg-like ATPase 22.86 4 0.00 || 4. 139856 Methylcrotonoyl-CoA carboxylase beta C9HCCO F chain, mitochondrial 22.80 6 0.00 || 4 6575.0 C9HC F Putative helicase WOW-O 22.2 4 OOO || 4 7452.5 RNA binding motif protein, X-linked C96E39 ke- 995 4. OOO || 4. O. CR8NF91 F Nesprin- 19.27 2 OOO a 80 26373 60S ribosoma protein 3 18.4 4. O.00 || 4 || OOO43.3 O726E9 F E3 ubiquitin-protein ligase RBBP6 18.4 3 OOO || 4 6174.5 CR.3247 Serinefarginine-rich splicing factor 6 1705 6 0.00 || 4 2.70658 Spectrin alpha chain, non-erythrocytic

Q13813 1 4,03 18 || 0.00 || 4. 86893.2 P4995 GMP synthase glutamine-hydrolyzing 13.84 8 O.OO || 4 99.978.O C.R.4789 r Golgin subfamily B member 1.94 12 || 0-00 || 4 803.7 CR8WWO Nuclear pore compex protein Nup133 143 3 O.OO || 4 1376.8 Epidermal growth factor receptor Q938C2 F substrate 15-ike 26 6 0.00 || 4 2976.O Q9NCH7 Probable Xaa-Pro aminopeptidase 3 1.07 6 || O.OO | A. 905.9 ATP-binding cassette sub-family F Q8NE1 neber O32 8 0.00 || 4 24539.9 CR5S25 Protein PRRC2B 9.33 4 O.OO || 4. O.O ETM1 and EF-hand corrain O952O2 containing protein 1, mitochondria 8.59 6 O.OO || 4 6249.5 P529O7 F-actin-capping protein subunit alpha- 7.92 A || O.OO || 4. 33269.3 C727K8 Centromere protein V 701 12 || 0.00 || 4 49439.0 Succinyl-CoA iigase ADP-forming Q92R7 F subunit beta, mitochondrial 6.80 8 O.OO || 4 5772.3 Succinyl-CoA iigase GDP-forming CR96899 Subunit beta, mitochondria 5.50 6 OOO 73283.5 Q5654 Thyroid receptor-interacting protein 6 5.39 4. O.OO | A. O.O. O96019 f Actin-like protein 6A 536 8 || O.OO || 3 3875.4 * Silac Directions Quantified: Forward (F) and for Reverse (R) Patent Application Publication Jul. 6, 2017. Sheet 42 of 141 US 2017/0192012 A1

F.G. 7

a e Top3 Uniprot. D Protein Nare Protein MW Ea & 3 Score F is PO5387 60S acidic ribosoma protein P2 1665.O. 8 92.2 O 483836 Heterogeneous nuclear P22626 ribonucleoproteins A2B1 387,749 28 85.0 1. 21347.18 P6074 riosephosphate isomerase 25.386.8 16 83.1 1. 191864 O5BKZ DBRD complex subunit ZNF326 53305.7 4 || 814 53O34 PC867 Winentin 537088 40 80.9 O 1113048 Heterogeneous nuclear PO9651 ribonucleoprotein A1 3.4223.8 24 79.4 10 832798 ATP synthase subunit beta, PO6576 mitochondrial 56560.0 28 || 77. O 587.965 60 kDa heat shock protein, PO809 mitochondrial S 225.9 A9 || 77.O 10 1562579 Guarine nucleotide-binding protein P63244 subunit beta-2-ike 35533.8) 9 || 76.3 O 2260.18 P51149 Ras-related protein Rab-7a 237749 4 || 76.3 10 152622 3-hydroxyacyl-CoA dehydrogenase Q9974 type-2 26.6816 2 76.3 10 1453O4. P35232 Prohibit 293611 14 || 75.7 t 3019 Ornithine aminotransferase, PO418 mitochondrial 4O7.6 8 748 10 23337 P60709 Actin, cytoplasmic 42O790 31 || 744 10 3998794 P23396 40S ribosomal protein S3 26859.4 8 || 74. O 28046 P553 Nucleoside diphosphate kinase A 18808 9 | 73.7 10 23040 P3OO44. Peroxiredoxin-5, mitochondria 19047.2 O | 73.5 O 71923 P22392 Nucleoside diphosphate kinase B 23888.7 2 72.4 O 1802OO P62258 14-3-3 protein epsilon 28O1 O. 19 || 71.0 10 2546.13 P62937 Peptidyl-prolyl cis-trans isomerase A 182406 3 || 70.9 O 350689 P25398 40S ribosomal protein S12 4942 8 70.5 O 186803 P49006 MARCKS-reated protein 19585.8 6 70.3 94.871 P63261 Actin, cytoplasmic 2 4235.1 3O S9.9 O 10 kDa heat shock protein, P61604 mitochondrial 1093.7 O 69.6 10 65924 P504O2 Entern 2905.9 1 69.3 10 51543 PO7437 tubulin beta chair 502.2 24 | 68.2 10 486040 O75947 ATP synthase subunit d, mitochondria 1789.3 9 67.9 O 16457 PO4O75 Fructose-bisphosphate aldolase A 39876.3 17 | 67.9 O 193818 P683.63 tubulin alpha-1B chain 5.0836. 22 87.6 1. 678591 P6837 tubulin beta-4B chain 50287.4 23 67.4 O 168285 Voltage-dependent anion-selective PA5880 channel protein 2 322777 5 | 670 10 329.663 P60660 Myosin tight polypeptide 6 17116.7 9 | 66.9 10 73250 P05386 60S acidic ribosoma protein P1 1628.0 3 66.7 10 543385.5 Mitochondrial import receptor subunit CR9NS89 TOM22 homolog 15521.7 5 66.2 10 184559 PA 866 Heterogeneous nuclear 57974.2 26 65.8 10 448298 Patent Application Publication Jul. 6, 2017. Sheet 43 of 141 US 2017/0192012 A1

F.G. 17 (cont'd) ribonucleoprotein L P6304 44-3-3 protein zetaldeita 2796.2 15 65.7 O 2.795 Heterogeneous nuclear P3942 ribonucleoprotein H3 26299. 15 64.7 O 2O3493 O7136 Tubulin alpha-1A chain 50820.O 21 64.5 O 439304 Q13885 Tubudir beta-2A chain 50306.3 20 64.5 O 1576.42 OSBWA Tubuli beta-2B chain 50409.4 20 64.5 O O P84077 ADP-ribosylation factor 2O753.8 10 64. O 231.94 O8 O7 heat shock 70 kDa protein A18 67279.9 34 64.0 O 654895 Vottage-dependent anion-selective 21796 channel protein 3O886.7 15 640 O 290A99 PO6733 Alpha-enoiase 42390.8 28 63.8 10 42982O C3HOU4. Ras-related protein Rab-1B 22342.3 3 63.2 O 16637 2070 ani-B 66693.6 39 62.8 1O 2898 Complement component 1 Q subcomponent-binding protein, Q07021 mitochondria 31765 62.8 10 7872 PO7737 Profi- 15225.3 8 62.1 O 26576 Q12905 Interleukin enhancer-binding factor 2 43290.3 16 82. 10 3O490 Acetyl-CoA acetyltransferase, P24752 mitochondria 45484.8 16 6.8 10 4854 1142 Heat shock cognate 7 kDa protein 62379. 34 6.7 O 622915. P1A618 Pyruvate kinase PKM 57994.4 25 61.6 10 255214 23528 Cofin-1 18730.6 11 615 O 193892 Q99623 Prohibitin-2 3117O.O. 17 6.2 O 20041 P62805 histone 4 11387.4 14 81.2 O 2465A960 Mitochondrial import inner membrane CR9YSL4 fanslocase subunit in 13 10728.2 7 6.1 1O 3OO90 P28599. Polypyrimidine tract-binding protein 58808 16 60 O 36664 Heterogeneous nuclear P698 ribonucleoprotein K 50453.2 22 60.9 O 3234.90 Q9JJZ Stomatin-ike protein 2, mitochondrial 38648.2 A 80.4 10 55633 C15365 Poly(C)-binding protein 380. 13 60.1 O 157355 Transitional endoplasmic reticulum 55O2 ATPase 900063 37 60.1 10 210496 P8282 Ras-related protein Rat-A 1758 1.7 9 60.0 O 1943 Single-stranded DNA-binding protein, CO4837 mitochondria 17259. O 59.5 O 263344 CR3162 Peroxiredoxin-4 30768.0 11 59.4 O 113355 CO8830 Peroxiredoxin-1 22338.5 2 89.3 O 26127 CR 12906 interleukin enhancer-binding factor 3 80654.7 32 59.2 10 28790 PO790 Heat shock protein HSP 90-alpha 91895.3 37 59.2 O 32394 Eukaryotic translation initiation factor P63241 SA- 18757.9 10 59.1 O S530 ATP synthase subunit alpha, P25705 hitochordria 57236.2 28 59.1 10 57.652 SAP domair-containing P82979 fibonucleoprotein 23727.9 9 59. 10 101782 Heterogeneous nuclear P31943 ribonucleoprotein H 4.9514.7 2 59.0 1O 633,389.5 P4941 Elongation factor Tu, mitochondria A9883.8 21 58.9 315477 O71J9 Histore 2A.W 115214 6 58.8 10 326748 Patent Application Publication Jul. 6, 2017. Sheet 44 of 141 US 2017/0192012 A1

FIG. 17 (cont'd) O9BOE3 Tubulin alpha-C chain 50579.7 21 58.8 10 55258O PO8238 Heat shock protein HSP 90-beta 83606.5 41 58.7 O 938.32 P68104. Eogation factor 1-alpha 504.83. 24 58.7 10 028420 P6106 Ras-related protein Rab-14 24 25, 1 12 58.6 O 33923 P4O926 Malate dehydrogenase, mitochondrial 35959.6 17 58.6 10 633463 PO3246 EB protein, small -antigen 2O785.5 9 58.5 O 210492 PO4908 Histone H2A type 1-BE 14135.5 7 58.5 10 47676O2 Membrane-associated progesterone O08264 receptor component 1 21785.2 10 58.5 O 125877 CR770 Histone H2A type 3 1425 7 58.5 O O 93.077 Histone H2A type-C 14105.5 7 58.5 O O Serine hydroxymethyltransferase, P34897 nitochondrial 552O7.5 23 58.4 O 255872 P62888 60S ribosomal protein 30 12955.2 6 58.3 10 281964 Far upstream element-binding protein O92945 2 734006 28 58.2 1. 236867 PO4350 tubulin beta-4A chain 50042.1 21 58. O 48 62 P 2004 Proliferating cell nuclear antigen 291 O 11 57.9 G 151656 ATP synthase subunit O, PA8047 mitochondrial 23394 11 57.8 O 105915 PO6748 Nucleophosrnir 3O298.7 16 57.7 10 2326268 P62244 40S ribosomal protein S5a A953.6 8 57.7 O 133667 P7837 -complex protein subunit beta 55445.2 23 57.6 10 46360 P61326 Protein mago hashi honolog 17220.7 7 57.5 10 102O76.5 P61204 ADP-ribosylation factor 3 2O657.8 10 57.5 10 O P548.19 Adeyate kinase 2, mitochondria 227544 14 57.3 O 139674 P38646 Stress-70 protein, mitochondrial 73965.8 36 57.3 10 383.168 P6224 40S ribosomal protein S8 24490,3 1O 57.2 O 31849 C9UQ80 Poiferation-associated protein 204 44.129. 20 57.1 O 84697 PO9874 Poly ADP-ribose polymerase 13882.4 46 57.0 O 593227 P60842 Eukaryotic initiation factor 4A-l 430794. 19 56.9 10 233346 Q96A72 Protein mago nashi honolog 2 17332,8 7 56.8 O 28669 Cytochrome c oxidase subunit 7A2, P44O6 mitochondria 9396.0 3 56.6 O 1494O6 PO541 ADPIATP transioCase 2 33O804. 17 56.4 O 65.349. C96KK5 Histone H2A type - 3908.3 6 56.3 O 3525 C998.78 Histone H2A type 1-J 13936.3 6 56.3 10 O P2236 AOPIATP transioCase 3 33094.4 15 56.O O 283704.5 Non-POU domain-containing octame CR 15233 binding protein 491.63. 23 56.0 10 3444 Small nuclear ribonucleoprotein Sm P62316 O2 13076.8 7 55.9 O 202066 P2277 Creatine kinase B-type 42929.5 6 55.9 O 227338 Signal recognition particle 14 kDa P37108 protein 146840 5 55.9 O 181806 Heterogeneous nuclear P51991 ribonucleoprotein A3 38540.2 2O 55.8 O 539225 Q16777 Histone H2A type 2-C 13988.4 7 55.8 10 14162340 O98TM1 Histone H2A. 15088,2 6 55.8 O O CR 1385 Chronobox protein honolog 3 20982.5 10 55.7 O 272259 Patent Application Publication Jul. 6, 2017. Sheet 45 of 141 US 2017/0192012 A1

FIG. i7 (cont'd) PA8643 T-complex protein 1 subunit epsilon 6O 274 2O 55.6 10 99198 Q6F13 Histone H2A type 2-A 40955 7 55.4 1O 6878,346 PCOS8 Histone H2A type 4.091.5 8 55.4 O O P20671 Histone H2A type 3-D 407.5 6 554. 10 O Cytochrome c oxidase subunit 5A, P2O674. mitochondria 6933.3 6 55.3 10 79914. leucine-rich PPR motif-containing P42704 protein, mitochondrial 59:02.9 59 552 10 25662 Trifunctional enzyme subunit alpha, PAO939 mitochondria 83742 29 54.8 10 168354 Q3838 Spliceosome RNA helicase DDX39B 5O291.7 19 547 10 457715 Small nuclear ribonucleoprotein Sm P8234 D1 13281.8 4. 54.6 O 279954 P08865 40S ribosomal protein SA 32968.2 12 54.6 10. 315535 P300.50 60S ribosomal protein L12 1680. 7 54.6 O 249512 P82979 Ubiquitin-40S ribosomal protein S27a 18307. 8 34.5 O 121 175 Glyceraldehyde-3-phosphate P844.06 dehydrogenase 36224.4 6 543 1. 507437 Q1518 norganic pyrophosphatase 336,3 543 O 85.077 Ran-specific GTPase-activating Pa3487 protein 234.812 7 342 O 216657 P82826 GTP-binding nuclear protein Ran 245942 9 S42 10 236830 P81247 40S ribosoma protein S3a 3C 73. 16 5.2 10 2O9411 P30041 Peroxiredoxin-6 2549. 11 540 10 80061 Putative nucleoside diphosphate O8O361 kinase 57OO.2 8 540 1C O 35268 60S ribosomal protein L22 14844.O 5 539 10 218082 POCOSS histore 2A.Z 13552.8 5 539 O O Q15366 Poly(rC)-binding protein 2 376915 53.7 O 2O9787 Putative elongation factor 1-alpha-like O5WTEO 3 50527.3 23 63.7 O O 2545 Preamin-AfC 68.737 29 53.2 O 94093 P3899 Eukaryotic initiation factor 4A-3 47156.3 21 530 1C 183078 Heterogeneous nuclear P52597 ribonucleoprotein F 46O4. 4 53.0 10 388906.1 P35244 Replication protein. A 14 kDa subunit 13682.8 5 529 9 28685 P394.6 4-3-3 protein betafalpha 28O80.4 52.9 O 642 P827O1 40S ribosomal protein S4, X isoform 29825.9 5 52.9 O 329836 O7553 Barrier-to-autointegration factor 10286.7 5 52.8 10 273447 Wesicle-associated membrane protein O95292 associated protein B/C 2742.1 9 52.7 O 53949 Q082 AP-dependent RNA helicase A 8333.9 43 52.6 10 354783 POCW22 40S ribosoma protein S17-ke 56O7.2 1O 52.6 10 188057 PO878 40S ribosomal protein S17 56O7.2 O 52.6 1. O PO7355 Annexin A2 397643 6 52.5 O 84.628 P6O4. Histone H2AX 154.46 6 52.5 O 6593O Q9Y265 Ruw8-ke 46548.2 9 524 O 97806 O8EUE6 Histone H2A type 2-8 13995.3 A 52.3 1O 262O8.5 P823O4. Sna: fluclear ribonucleoprotein E 1086O7 5 522 O 339.177 Nuclease-sensitive element-binding PS7809 protein 35924.2 9 52.2 10 255485 Patent Application Publication Jul. 6, 2017. Sheet 46 of 141 US 2017/0192012 A1

FIG. 7 (cont'd) Electron transfer flavoprotein subunit P13804 alpha, mitochondria 32837.8 O 52.1 10 26.410 P628 40S ribosonal protein S7 22126.9 8 5.2.1 1C 1678.36 PO5388 60S acidic ribosomal protein P0 34444.7 13 51.7 O 34428 Heterogeneous nuclear O43390 ribonucleoprotein R 713640 25 51.7 10 2927 P300 Protein disulfide-isomeraseA3 571816 23 51.7 O 50648 P828O7 Histone H2B type 1-C/E:FIG/ 13906.2 2 56 O 2O597OO P33778 Histone H2B type 1-B 13950.2 12 51.6 O 52.55009 O6084 Histone H2B type 3-K 3890.2 2 5.6 O O PO6899 Histone H2B type - 39042 12 51.6 10 O 23527 Histone H2B type 1-0 13906.2 2 51.6 O O P58876 Historie H2B type i-D 13936.2 12 51.6 O C Q16778 Histone H2B type 2-E 39:20.2 2 516 O O Q5QNW6 Histone H2B type 2-F 4.380.8 12 51.6 1O O O930F9 Histone H2B type t-H 13892.1 2 51.6 O O Q99877 Histore 2B type 1-N 392.2.2 2 56 O O O99879 Histone H2B type 1-M 13989.3 12 51.6 O O Lamina-associated polypeptide 2, P4267 isoforms betagamna 44761 5 515 O 2398.17 transcription intermediary factor 1 O 13263 beta 854.945 26 54 10 1O7832 DNA-apurinic or apyrimidinic site) P27695 lyase 359537 11 51.3 1.O. 72474 P84085 ADP-ribosylation factor 5 2O643.8 7 51 O 8637.82 O9JHX1 Poly(U)-binding-spicing factor PUF60 S6888.5 9 51 O 967S3 Q9NR30 Niceolar RNA helicase 2 8403.9 36 51 10 26239 Heterogeneous nuclear O60506 ribonucleoprotein Q 60817.8 24 51.0 O 2O332 O8642 Polyadenylate-binding protein 2 32237.O 9 5. 10 133635 O9NR31 GP-binding protein SAR1a 22489 7 5 O 10 61938 Probable ATP-dependent RNA P1784.4 helicase DOX5 696.614 27 5 O 1C A4388 Guarine nucleotide-binding protein PS2873 G();G(S)G() subunit beta- 38175.4 1 50.9 10 48622 P1905 Myosin regulatory light chain 12A 19851.2 8 50.9 10 5976 Pyruvate dehydrogenase E1 component subunit alpha, somatic PO8559 form, mitochondria 444,632 2 508 O 12047 Q07955 Serinefarginine-rich splicing factor 2759.3 a 50.8 O 32575 Q13748 tubin alpha-3CD chain 487.20.3 6 50.7 O O Q13242 Serinefarginine-rich spicing factor 9 25656.3 13 50.7 1. 42482 P27348 14-3-3 protein theta 28049A 13 50.6 10 644.6423 16989 Y-box-binding protein 3 36352.6 1 50.6 1O 32224 O4950 Myosin regulatory light chair 12B 19836.2 8 50.6 O O Q99832 -Complex protein subunit eta 509618 2O 50.5 O 12575 P3O84. Enoyl-CoA hydratase, mitochondrial 38437 13 50.3 1G 95.422 PO4637 Cellular tumor antigen p53 35393.1 2 50.3 O 67303 P8396 Chronobox protein homolog 21539 8 50.3 10 1323.77.1 CR994.97 Protein D- 2006.2.2 6 88.3 10 8648 P37802 transgelin-2 22562.6 O 50.3 O 57,082.5 Patent Application Publication Jul. 6, 2017. Sheet 47 of 141 US 2017/0192012 A1

FIG. 17 (cont'd) O9JMS4 Pre-mRNA-processing factor 9 55637.1 4 50.2 O 17452 P22234 Mutifunctional protein ADE2 482.46.8 18 50.1 10 59268 P62750 60S ribosomal protein 23a 17695. 9 50.0 O 373350 Q9H984 Sideroflexin-1 35904.6 2 5O.O 10 13586 P1A625 Endoplasmin 92754.2 38 49.8 1O 245779 P 102 78 kDa glucose-regulated protein 72447. 29 49.7 O 31905.6 PSO991 -compex protein 1 subunit deta 56835.2 2 49.5 10 10288 Mitochondria: import inner membrane O6022O transiocase Subunit in 8 A 1226.5 4. A9.5 9 3,542 P18085 ADP-ribosylation factor 4 20624.9 8 49.4 O 69412, 18 Regulator of chromosome P 18754 Condersation 4707O6 3 49.4 O 103.79 P10599 hioredoxi O957.9 4. A9.4 1C 50907 PO795 --lactate dehydrogenase B chain 36923.7 15 49.4 O 350.583 39S ribosoma protein 53, O96E-3 mitochondria 2277.9 4 49. 4 O P17987 -complex protein 1 subunit alpha 60856.9 2 49. 10 12282 Heterogeneous nuclear P52272 ribonucleoprotein M 75853.8 34 49.1 10 256246 P6 O 9 Ras-related protein Rab-2A 22339.1 8 49.1 10 79446 P981 79 Putative RNA-binding protein 3 17170.4 5 49.0 O 51972 P22087 rRNA 2'-O-methyltransferase fibrillarin 33898.3 O A8.9 10 14282 POO338 L-lactate dehydrogenase A chain 3309.5 5 48.8 O 28O34 Heterogeneous nuclear P55795 ribonucleoprotein H2 4.9548.8 2 48.8 O 67604.4 Ribosomal RNA snai subunit O92979 nethyltransferase NEP 26948.3 8 48.8 9 4808 Far upstream element-binding protein O9624 3 46934.9 4 48.7 1 O 5O277 P99999 Cytochrone C 1862.8 6 48.6 10 8235.5 C7 D3 Histone H3.2 15445. 7 48.5 O 1941 783 P84243 Histone 3,3 15385.0 6 48.5 1. 9297.59 CR 16629 Serinelarginine-rich splicing factor 7 21280.4 7 48.5 10 28.245 Thioredoxin-dependent peroxide P300.48 reductase, mitochondria 28O34.8 9 48.4 10 395 O6 X-ray repair cross-complementing P12956 protein 6 70283 25 48.4 10 152542 Cytochrome b-c1 complex subunit 6, PO799 mitochondria O23.9 2 48.4 4. O Q96 PK6 RNA-binding protein 14 37785.1 3 48.3 10 121369 Mitochondria import inner membrae C9Y57 translocase Subunit in 9 0606.0 4. 48.3 2 O rifunctiona: enzyme subunit beta, P55084 mitochondria 51579.7 8 || 48. O 98.049 P329 Peroxiredoxin-2 22063.O tO 48.0 O O P6224 Ras-related protein Rap-1b 8000.5 9 47.8 10 61363 P62333 26S protease regulatory subunit OB 44,458.2 12 47.8 10 30516 Succinyl-CoA tigase (GDP-forming O9699 subunit beta, mitochondrial 4752O6 7 47.7 10 323 P14854. Cytochrome c oxidase subunit 6B O420.5 3 47.7 7 7868 Small nuclear ribonucleoprotein Sn P6238 D3 4030.4 6 47.6 10 324862.5 P5753 Histone H2B type F-S 139442 O 47.6 O O Patent Application Publication Jul. 6, 2017. Sheet 48 of 141 US 2017/0192012 A1

F.G. 17 (cont'd) Q9988O Histone H2B type 1- 139522 11 47.6 10 O P2664 Elongation factor 1-gamma 5046 O 18 47.8 10 70927 P 8124 60S ribosomal protein 7 2.9282.9 2 47.6 1. 264360 Leucine-rich repeat-containing protein Q96AG4 59 35329.7 13 47.8 10 80.783 Staphylococca nuclease domain Q7KZF4. containing protein O2684. 32 Af.4 10 7679 O43852 Caineni 267988 8 47.3 10 37707 O60828 Polyglutanine-binding protein 246586 4 473 8 O P8869 Phosphoglycerate mutase 28918O 9 47.2 10 18832 NADH dehydrogenase ubiquinone 1 OOO483 alpha sbcomplex subunit 4 94.26.9 A. 46.9 10 1 1884.5 P2O290 Transcription factor BF3 19962.1 8 46.9 1O O C 3595 Transformer-2 protein homolog alpha 23 1955 7 46.9 10 73303 Q9YSS9 RNA-binding protein 8A 19885 6 46.8 O 107058 SRA stem-loop-interacting RNA O9GZ3 binding protein, ritochondria 12406.1 4 46.8 A. O P27797 Caetic in 433 12.7 A 46.8 10 255350 C86W81 ThO complex subunit 4 26887.9 O | A6.7 O 32,147 P24534 Elongation factor -beta 24934.8 7 A6.7 O 203209.5 O6PEY2 Tubulin alpha-3E chain 506000 2 A6.7 O O Q9Y230 RuvB-like 2 53278 2O 46.7 10 77 86 POO558 Phosphoglycerate kinase a5O140 13 46.5 O 945AO Cytochrome b-c complex subunit , P31930 itochondria S333O2 14 46.5 10 152049 P62829 60S ribosomal protein 23 14979.5 6 46.4 10 28.60 P62857 40S ribosomal protein S28 7898.1 4. 46.4 1. 276387 PhD finger-like domain-containing C7.RVO rotein 5A 13468 26379 O43707 Alpha-actinin-4 1053304 3 46.3 10 1629.15 OOO567 Nucleolar protein 56 66449.2 113935 P62995 Transformer-2 protein honolog beta 27914.5 46.3 10 21986 P1798O 26S protease regulatory subunit 6A 494.88.8 4 A6.2 O 2719.3 Probable ATP-dependent RNA O9284 helicase DDX17 7SOF72 33 46.2 10 2146.8 RNA-binding motif protein, X 381.59 chronosore 351548 16 46.0 O A-52996 Vesicle-associated membrane protein CR 5836 3 1366.1 3 46.0 8 O 116 kDa U5 Small nuclear C 5829 ribonucleoprotein component 18379.4 27 A6. O 11663 Woltage-dependent anion-selective Q9Y277 channel protein 3 31 O86.5 10 45.9 10 150127 P6833 Actin, alpha skeletal muscle 42393.3 8 45.9 O 1707,962 P 18621 60S ribosoma protein 17 9445.2 8 A5.9 O 166130 Peptidyl-prolyl cis-trans isomerase F, P30405 nitochondria 223824 7 45.9 8 O Heat shock protein 75 kDa, Q12931 hitochondria: 80395.3 24 45.9 10 272558 NADH-ubiquinone oxidoreductase 75 P2833 kDa subtit, mitochondria 76268.O 23 A5.8 O 783O8 Peptidyl-prolyi cis-trans isomerase CO2790 FKBP4. 520898 8 45.8 10 5856 Patent Application Publication Jul. 6, 2017. Sheet 49 of 141 US 2017/0192012 A1

FIG. 17 (cont'd) P2964 Catecho O-methyltransferase 27678 8 45.7 1C 2774 P552O9 Nucleosome assembly protein t-like A5659.3 1 45.5 1O 34.732 X-ray repair cross-complementing P13010 protein 5 832750 23 45.5 10 1A9036 P3639 Elongation factor 2 963078 33 45.5 10 21.8889 POO387 NADH-cytochrome b5 reductase 3 3496.2.8 9 43.3 t 8.192 P56537 Eukaryotic translation initiation factor 6 212.4 7 45.3 10 O2975 Splicing factor, proline- and gutamine P23246 rich 4320.5 23 43.3 10 451035 O75367 Core histore macro-H2A.1 398.9 13 45.3 10 155967 P62424. 60S ribosoma protein L7a 30166.7 3 45.1 1O 213545 P4314. Glucosidase 2 subunit beta 602713 16 45.1 10 108670 62.277 40S ribosomal protein S13 17222.3 8 45.0 O 2693 P56385 ATP synthase subunit e, mitochondria 933.2 3 44.9 8 23208 Heterogeneous nuclear C1315 ribonucleoprotein A0 3101.7 O 44.9 O 22657 P39C9 40S ribosomal protein S19 660.5 O 44.8 10 164.628

QG2878 60S ribosoma protein 6 32785.O 3 44.8 1G 72539 PO7237 Protein disulfide-isonerase 57515.6 9 44.7 1G 6864. 46782 40S ribosoma protein S5 23047.5 9 44.6 O 33488 PS322O 40S ribosomal protein S21 92.28.5 5 44.6 1O 95286 PO3247 E1B protein, snal T-antigen 2O6854 44.6 || 10 O O4369 Cytochrone b5 type B 6446.2 4 44.5 10 22A454 Lamina-associated polypeptide 2, PA266 isoform alpha 760624 9 44.5 10 44777 ATP-dependent RNA helicase OOO 48 DOX39A 49842.9 4 44.5 10 379,707 Q1577 EAV-like protein 3626.30 11 445 O 752O7 ATP synthase-coupling factor 6, P18859 nitochondria 13016.5 5 44.4 6 O Heterogeneous nuclear PO791) ribonucleoproteins CfC2 29876.O. 5 44.4 O 5897a.5 O75533 Splicing factor 3B subunit 46572O 38 443 O 37433 Q53-12 Acylglycerol kinase, mitochondria A75934 14 44.3 10 69477 Signal recognition particle receptor Q9Y5M8 sount beta 29930.4 8 44.3 8 33849 Peptidyl-tRNA hydrolase 2, O9Y3E5 nitochondria 19478.7 5 44. 8 O P50990 -Conpex protein subunit theta 6O1910 23 44. O 2871 PO921 Glutathione S-transferase P 235.840 7 43.8 1. 15014 U5 small nuclear ribonucleoprotein 40 Q967 kDa protei 39.7868 9 43.7 1C 52647 Hydroxyacyl-coenzyme A Q6836 dehydrogenase, nitochondria 38416.2 7 43.6 10 78489 PS297 60S ribosonal protein L3 28252.8 8 43.6 10 75299 Eukaryotic translation initiation factor CR 5056 4H 26349.5 7 43.6 O O PS8032 Actin, alpha cardiac muscle 1 42362 17 43.5 1O 163892 P62834 Ras-related protein Rap-1A 2329.4 7 435 1O 61.22 Plasminogen activator inhibitor RNA Q8NCS binding protein 43753.1 3 43.4 10 195707 COO6:O Catheir heavy chain 1952O7 Sf 43.4 1O 14975 Patent Application Publication Jul. 6, 2017. Sheet 50 of 141 US 2017/0192012 A1

FIG. 7 (cont'd) Pa9368 T-complex protein 1 subunit ganna 590243 9 a.3.3 O 125968 P68366 Tubulin alpha-4A chain 5665.8 18 43.3 O O P 4927 Cytochrone b-c1 compiex subunit 7 4718. 6 || 43.2 O 69797 Q9Y2X3 Nucleolar protein 58 6309.5 8 43.1 O 4263 Up-regulated during skeletal muscle O96X5 growth protein 5 6546 2 43. 8 8388O Eukaryotic translation initiation factor 3 C3347 Subunit 389C11 11 43. 6 16366.5 P23284. Peptidyl-prody cis-trans isometase 8 23799.6 11 43.1 O 25733 P5 A8 Ras-related protein Rab-3C 25872 9 || 43. 10 94568 P6228O 40S ribosoma protein S11 186O18 7 || 430 O 32687 CO3252 Lannin-B2 678O3,O 26 || A3.0 1O 13659 O43684 Mitotic checkpoint protein BUB3 37482.4 O | A2.9 1O A564 96.3208 S-phase kinase-associated protein 85318 6 A2.9 10 2854 P3563 Basign 286340 7 || 42.9 O 2G2386 Glutamate dehydrogenase 1, POO367 itochondria 63740.1 9 42.8 O 806O7 P62269 40S ribosoma protein S18 17718.7 9 A2.8 O 229377 O756O7 Nucleopasnin-3 19628.9 4. A2.7 O 16862 O9 KO2 nRNA turnover protein 4 honolog 276746 18 42.7 O 14466.5 P223C7 Non-specific ipid-transfer protein 42962 3 || 42. O 3458 P6353 60S ribosoma protein 27 15797.8 6 || 42.7 O 267358.5 P43243 Matrin-3 79027.5 26 || 42.6 10 2722O7 P12235 ADPAP transiocase 33292.7 3 || 42.6 O 4882.61 Translationally-controlled tumor P3693 protein 19709.5 4 || 42.4 O 44 OO P2824. Cainexin 68O246 20 || 424 O 4.04790 P62736 Actin, aortic smooth muscle 424.08.3 8 || 42.2 10 787849 P 3667 Protein disfide-isomerase A4 73274.7 24 || A22 O A4490 P61981 14-3-3 protein gamma 284.737 1 A2. O 6981473 O8N257 Histone h2B type 3-8 13908. 10 42. O O P34932 Heat shock 70 kDa protein 4 951865 24 || 42. O 8487 Serine-threonine kinase receptor C9Y3F4 associated protein 3878.5 13 420 9 A2.218 O53GCRO Estradio 17-beta-dehydrogenase 2 34.4383 1 || 42.0 O 67896 PO966 U2 smail nuclear ribonucleoprotein A 28529.7 9 || 42.0 O 8295 OOO299 Chioride intracellular channel protein 1 272649 8 || 419 5 Q6P48 Aspartate-tRNA ligase, mitochordsia: 74.133. 8 || 41.9 O 8983 O43175 D-3-phosphoglycerate dehydrogenase 57392.O 7 || 48 10 134955 Eukaryotic translation initiation factor 3 O15371 soit D 64600.2 3 || 418 O 37314 N-alpha-acetyltransferase 38, NatC O95777 auxiliary subunit 0402.7 2 4.7 8 O F-actin-capping protein subunit alpha P52907 1 33093.9 8 || 46 9 4490 CR5393 Splicing factor 3B subunit 3 7O663.3 33 A6 O 151768 PO895 4F2 ceil-surface antiger heavy chain 64.89.8 18 46 O 11277 U small nuclear ribonucleoprotein 70 PO8621 kDa 40467.9 4 || 4.6 O 35948 Q9Y281 Cofilin-2 3850. 6 || A.6 1O Patent Application Publication Jul. 6, 2017. Sheet 51 of 141 US 2017/0192012 A1

FIG. 7 (cont'd) Heterogeneous nuclear COO839 ribonucleoprotei U 90.5235 29 46 1O 1241 A8 P82987 Ubiquitin-60S ribosonal protein 40 1503.5 8 44 10 O Aspariate aminotransferase, POO505 initochondria 4796.9 3 || 44 O 2558 25789 Proteasome subunit alpha type-4 27539.1 7 414 O O P1588 40S ribosomal protein S2 3169.6 2 413 10 188868 P853 60S ribosomal protein 37a 10503.4 A. 41.3 1. 83443.5 ASNWY6 Putative annexin A2-like protein 38830.2 4 43 O NADH dehydrogenase ubiquinone O75489 iron-sulfur protein 3, mitochondria 303556 O 413 O 62482 CRO7065 Cytoskeleton-associated protein 4 66.36.6 9 42 O 7988 C70Y3 Mitochondria Fibonuclease P protein A632.2 4 A2 O 12333 Electron transfer flavoprotein subunit 381 7 beta 3292.42 10 42 10 103627 HiACA ribonucleoprotein complex C9NX24. subunit 2 17543.2 3 4.2 9. O Q15084 Protein disulfide-isornease A6 54.67.4 15 411 O 8524.4 C982Z5 Apoptosis inhibitor 5 535838 15 411 10 84034 P82249 40S ribosomal protein S6 16559.4 7 4. 10 163437 Q727K6 Centromere protein W 26750.9 6 4.1 10 8234.15 P19338 Nucleolin 76675 28 410 10 86O18 Heterogeneous nuclear O499 ribonucleoprotein D-like 35904 13 410 O 64042 Serine/threonine-protein phosphatase P82140 PP1-beta catalytic subunit 37985.3 13 40 10 365.45 P28838 Cytosol aminopeptidase 34.99.5 18 40 1O 42561 CR3509 Tubulin beta-3 chain 50889.) 16 40.9 O 21054:37 Apoptosis-inducing factor , O9.583 nitochodia 4.6729.6 8 || 408 O 1727 14 385.8 60S ribosomat protein L4 47982.5 15 4.08 O 24653 CR96771 N-alpha-acetyltransferase 50 14545.7 4. 4.7 2 O COO57 ATP-dependent RNA helicase DOX3X 726986 28 40.7 O 109A.86 P63267 Actin, ganna-enteric smooth muscle 39879.4 16 40.7 10 O O43504 Ragulator complex protein AMOR5 9785.O 3 40.7 2 O CR99798 Aconitate hydratase, mitochondrial 8666.9 23 40.6 10 82553 Heterogeneous nuclear CR1403 ribonucleoprotein 0 34724.4 16 40.5 10 750997 O12788 Transducin beta-like protein 3 90403.4 22 4.5 O 34687 O75934 Pre-mRNA-spicing factor SPF27 262456 6 40.4 8 O hypoxanthine-guanine PO492 phosphoribosyltransferase 2A807.5 8 40.4 O 54.399 C9HB7 Calcyclin-binding protein 263240 9 40.4 8 84390 Heterogeneous nuclear C32P5 ribonucleoprotein A1-like 2 3439.65 6 40.3 1. O Q6891 Mitochondria inner mentarare protein 82509.2 23 40.3 10 O5552 Dolichyl-diphosphooligosaccharide-- PO4844 protein glycosyltransferase subunit 2 68560.8 8 403 O 54450 P28583 High nobility group protein B2 242O4.9 O 40.2 1. 357.762 Mitochondria 2-oxoglutaratelmalate QO2978 carrier proteir 34.232.9 11 40.1 1. 9788 PO3243 EB protein, large f-antigen 36737.2 14 4.0.1 O 263160 Patent Application Publication Jul. 6, 2017. Sheet 52 of 141 US 2017/0192012 A1

FIG. 17 (cont'd) Dolichyl-diphosphooligosaccharide PO484.3 protein glycosyltransferase subunit 68683.6 20 | 40.0 O 44842 U5 sma: nuclear ribonucleoprotein O75643 200 kiba helicase 159045. 53 | 400 10 982O7 PO5455 lupus La protein 47008.2 17 | 40.0 10 9.1736 CR 15907 Ras-related protein Rab-1 B 24.602.6 8 39.9 10 56882 O9Y35 Ras-related protein Rap-2c 20972.9 y 39.9 2 O Q15459 Spicing factor 3A subunit 1 88943.4 24 || 39.9 10 95595 P55769 NHP2-like protein 1440.7 5 || 39.8 O 200719.5 Peroxisoma multifunctional enzyme PS1659 type 2 80784.4 2O || 39.8 18 932O P3 948 Stress-induced-phosphoprotein 63266.7 21 || 39.8 O 144263 Delta-1-pyrroline-5-carboxylate P54886 synthase 87937.2 26 || 39.8 10 138902 P46,781 40S ribosomal protein S9 22648.5 39.7 10 O3515 Cytochrome c oxidase subunit 4 p13073 isofor , initochondrial 19633.8 7 39.6 10 16916 Guanine nucleotide-binding protein PO4899 G(i) subunit alpha-2 403740 2 || 39.6 10 O Q9Y3Y2 Chronatin target of PRM1 protein 24.946.6 8 39.6 O 86550 PO9429 High nobility group protein B1 25064.9 9 39.5 10 O P62633 Cellular nucleic acid-binding protein 2O27.O 5 || 39.5 6 O Serine/threonine-protein phosphatase P62 36 PP-alpha catalytic subunit 388417 2 || 39.4 1 O 794.75 O96A08 Histone H2B type 1-A 14 675 S 394 O 1265668 P42677 40S ribosomal protein S27 98O3.3 4 || 39.3 O 2143 Succinate dehydrogenase ubiquinone iron-sulfur subunit, P21912 mitochondrial 32428.2 8 39.3 10 8688 P26368 Spicing factor U2AF 65 kDa subunit 53653.O. 39.3 10 228992 Glutamate-rich WD repeat-containing O98O87 protein 4988.4 1O || 39.2 O 51483 Microtubule-associated protein RP/EB O15691 family member 1 370.2 8 39.2 5 O P29692 Elongation factor -delta 404,042 9 || 39.2 1. 135247 Sodium/potassium-transporting P0523 ATPase subunit alpha- 1000598 31 || 39.1 10 153692 Q05639 Elongation factor 1-alpha 2 50824 2 || 39.1 10 25978 Surviva of motor neuron-related O75940 splicing factor 30 26882.2 5 || 39.1 4. O P1652 Carbony reductase NADPH 1 3066O1 9 39.0 4. O Q9NY65 Tubulin alpha-8 chain 47122.5 12 || 38.9 O O Heterogeneous nuclear O997.29 ribonucleoprotein A/B 33484.5 3 || 38.9 O 721232 P27635 60S ribosomal protein 10 2506O2 8 388 1 O 185573 Pre-mRNA-processing-splicing factor O6P2C9 8 2749 2.5 65 || 38.8 10 21 65 Pyruvate dehydrogenase E1 p1177 component subunit beta, mitochondrial 38.3249 2 || 38.7 10 70.256 Bifunctional purine biosynthesis P31939 protein PURH 6529.2 18 || 38.7 9. 352935 P28O86 Proteasome subunit alpha type-5 23873.4 6 38.6 O 5756 Q14974 importin subunit beta-1 984-82.0 24 || 38.6 O 12940 P84090 Enhancer of rudimentary honolog 243CO 5 || 38.5 10 1066 Patent Application Publication Jul. 6, 2017. Sheet 53 of 141 US 2017/0192012 A1

FIG. 17 (cont'd) O9Y2CR5 Ragulator complex protein AMTOR2 14729.3 6 38.4 4. O4240 Eukaryotic initiation factor 4A-1 466740 3 383 10 inorganic pyrophosphatase 2, O9H2U2 mitochondria 336321 38.3 O 61155 O9Y2O3 Glutathione S-transferase kappa 1 25562.2 6 38.3 10 624.24 Trifunctional purine biosynthetic P22102 protein adenosine-3 83O38.O 16 38.1 31076 O71 UM5 40S ribosomal protein S27-like 98.19.3 3 38.1 O 863.O. Succinate dehydrogenase ubiquinone flavoprotein subunit, P3O4.O. mitochondria 737 8. 5 380 10 98997 P62195 26S protease regulatory subunit 8 45376.2 12 37.9 O 36980 P2807O Proteasone subunit beta type-4 29261.4 7 37.9 O 72669 Enoyl-CoA delta isomerase 2, O75521 mitochondrial 4968.O 10 37.9 10 28O35 Q9Y617 Phosphoserine aminotransferase 38396.8 11 37.8 O 51059 Aminoacyl tRNA synthase complex O2904 interacing nutifunctional protein 36009.6 8 37.8 10 O 234.13 Serinelarginine-rich spicing factor 3 19557.7 8 37.8 O A954:34 Activated RNA polymerase I P53999 transcriptional coactivator p 15 14395.4 5 37.8 10 124O29 O994.59 Ce: division cycle 5-like protein 92.4789 22 37.8 10 54.633 262263 40S ribosoma protein S4 18443.8 7 37.8 10 2O7925 28S ribosomat protein S34, P82930 mitochondria 25.707.5 5 37.6 10 1826 P40616 ADP-ribosylation factor-like protein 1 25.316 4 376 7 220.98 p61026 Ras-related proter Rab-10 22 769. 6 375 10 138828 isocitrate dehydrogenase NAD P50213 subunit alpha, mitochondria 35942.8 2 37.5 10 82793 PO6493 Cyclin-dependent kinase 30827.7 O 37.5 10 321.95 Transcription elongation factor B O15369 polypeptide 12O78.4 3 37.5 6 O Serine/threonine-protein phosphatase P36873 PP1-gamma catalytic subunit 38492.5 1 37.5 1. 17700 histidine triad nucleotide-binding O9BX68 protein 2, mitochondrial 728.8 4. 37.4 7 P6586 Transforming protein RhoA 221 O.3 7 37.3 O 72332 Guanine nucleotide-binding protein PO8754 G(k) subunit alpha 4102.5 2 37.3 10 437.82 P39023 60S ribosoma protein 3 463941 5 37.2 10 188885 Calcium-binding mitochondria carrier O9 SO protein Aralar2 A4838.9 18 37.2 10 45564 Serine/threoline-protein phosphatase 2A 65 kDa regulatory subunit A alpha P3O153 isoforin 66 107.1 20 37.2 1O 54942 PO3244 EB 55 kDa protein 56334.5 13 37.2 O O5019 Septin-2 43730.9 11 37.1 O 3956 P63167 Dynein light chain , cytoplasmic 10537.O 3 37.1 O 188058 P60900 Proteasome subunit alpha type-6 278557 8 37.0 10 39.036 ET/1 and EF-hand domain O952O2 containing protein 1 mitochondrial 58660.4 2 36.9 O 72336 Aldehyde dehydrogenase, P05091 ritochondria 56894.6 17 36.9 10 6541 CO2543 60S ribosomal protein 18a 21047.5 8 36.9 O 182385 Patent Application Publication Jul. 6, 2017. Sheet 54 Of 141 US 2017/O192012 A1

FIG. 7 (cont'd) O9Y384 Pre-mRNA branch site protein p14 14899.0 4 36.8 10 17678 Far upstream element-binding protein O96AE4 68282.2 2O 36.8 10 113678 Q9983 Protein arginine N-methyltransferase 1 4O983.4 12 36.7 O 39372 Q9GZ7 Ribosome biogenesis protein WDR12 48223 1 36.6 10 439.62 PA3897 Elongation factors, mitochondrial 36838.6 8 36.6 10 56373 Ribosome biogenesis protein BRX1 Q8DN6 homolog 41686.6 12 36.5 10 O C9Y224 UPF0568 protein C14orf166 28822 9 365 1O 33.130.5 C 2849 G-rich sequence factor 1 4522. 13 36.5 O P32969 60S ribosomal protein L9 21977.5 6 36.5 O 213925 Thioredoxin domain-containing protein O8N8S9 5 42530.7 1 36.4 O 48.192 O99986 Serine/threonine-protein kinase WRK1 45883 O 36.4 9 C Alkyldihydroxyacetonephosphate O0016 synthase, peroxisomal 737 O.3 16 36.3 1. 50.115 O9B V4 Transmembrane protein 43 44932. 13 36.3 4. O Sodium/potassium-transporting P54709 APase subunit beta-3 3854.8 7 38.2 1. 35741 Cytochrome b-c1 complex subunit 2, P22695 mitochondria a88142 13 36.2 10 11908 P54577 Tyrosine-tRNA ligase, cytoplasmic 59485.7 17 | 36.2 1. 43046 Wesicle-associated membrane protein Q9POO associated protein A 30481.8 8 36. 10 3030.5 P206.8 Proteasone subunit beta type- 26775 9 36. O 460.85 26S proteasome non-ATPase P55036 regulatory subunit 4 352862 9 36. 10 32247 Eukaryotic translation initiation factor 2 P20042 subunit 2 3873O8 9 360 10 35292 QO8945 FACT complex subunit SSRP 8417. 22 360 10 7.342 P294.01 asketoase 6903O. 14 360 10 6980) 28S ribosomal protein S7, O9Y2R9 ritochondria 28248.2 10 36.0 7 O O75964 ATP synthase subunit g, mitochondrial 1428.5 3 35.9 6 41.63 P492O7 60S ribosomal protein L34 135211 5 35.9 O 554.445 P46779 60S ribosomal protein 28 8022.5 5 35.8 10 884.28 Mitochondrial import receptor subunit O98008 TOM40 homolog 36935.6 9 35.7 O 8637 C96CS3 FAS-associated factor 2 52965.7 35.7 O 65875 Eukaryotic translation initiation factor C6S 14 5A--like 170013 6 35.7 1. O 1474 Macrophage migration inhibitory factor 2647.4 3 35.7 O 30662 P46060 Ran GTPase-activating protein 1 63998.3 6 35.6 10 43963.5 Small nuclear ribonucleoprotein G-like A8MWD9 protein 860. 3 35.5 O 10577 Q9MVP1 AP-dependent RNA helicase DDX18 75749. 19 35.4 10 OO74 QO7812 Apoptosis regulator BAX 2O661. 6 35.4 10 3824. 39S ribosomal protein 12, P5285 mitochodia 21576.3 6 35.4 10 250710 Ras-related protein Rap-1b-like ASNZ protein 253.0 6 35.3 O O Ribosomal t-1 domain-containing O76O2 protein 552OO.7 16 35.3 1. 47493 Patent Application Publication Jul. 6, 2017. Sheet 55 of 141 US 2017/0192012 A1

FIG, 7 (cont'd) O14697 Neutral alpha-glucosidase AB O862.4 26 35.3 1.O. 1313.35 P61006 Ras-related protein Rab-8A 238393 7 || 35.3 10 254O7.88 ATP synthase F(0) complex subunit P24539 81, mitochondria 289657 8 35.2 10 70389 O75494 Serinefarginine-rich spicing factor 10 25250.6 6 35.2 10 3805 Q96OV6 Histone H2A type A 4233.5 5 || 35. 1 O 0.5594 P60604 Ubiquitin-conjugating enzyme E2 G2 17261.2 3 35.0 2 O p6293 60S ribosomat protein L1 20416.5 5 || 35.0 10 190835 P35250 Replication factor C subunit 2 38048.1 7 35.0 5 2283 P62906 60S ribosomal protein L10a 25002.4 9 || 35.0 O 495.08 O14579 Coatomer subunit epsilon 3.1828.9 1 || 35.O 8 O P28074 Proteasone subunit beta type-5 24,149.0 8 || 35.O O 19476 Spectrin alpha chain, non-erythrocytic O 13813 1 284,770.5 71 || 350 10 76179 P62266 40S ribosomal protein S23 15978.7 4. 35.0 O 47 147 P61225 Ras-reated protein Rap-2b 2O732.5 5 35.0 2 O P3493 Heat shock 70 kDa protein -like 7077.4.3 17 | 35.0 10 33876.34 P194G Polyadenylate-binding protein 661542 22 || 34.9 10 32868 Medium-chain specific acyl-CoA p1130 dehydrogenase, mitochondria 47288.9 13 || 34.9 10 64702 Signal recognition particle 9 kDa P49458 protein 9892.9 4 || 34.9 1 O. 135312 Endoplasmic reticulum resident P300.40 protein 29 25682.8 7 || 34.9 O 6844 Sterol-4-alpha-carboxylate 3 O15738 dehydrogenase, decarboxylating 42185.5 10 || 34.9 10 4.1651 DNA-dependent protein kinase p78527 catalytic subunit 4.72257.O 34.8 10 4.583 Protein--isoaspartate(D-aspartate) O P22061 methyltransferase 24829.0 8 || 34.8 1 O. SO952 O75937 Ona honolog subfamily C member 8 2984.7 7 || 348 8 O P12532 Creatine kinase U-type, mitochondrial 4985, O 1 || 348 10 92481 Eukaryotic translation initiation factor P4783 1A, X-chromosoma 165745 5 34.7 10 O POO67 Cytochrone b5 3589. 3 || 34.7 10 O P50395 Rab GP dissociation inhibitor beta 4.8807.8 2 || 34.6 10 53428 CO7020 60S ribosomal protein 18 21748.6 6 34.6 10 431140.5 Q9Y589 FACT complex subunit SPT16 1204.84.3 3O || 348 10 195707 Eukaryotic translation initiation factor 2 P409 subunit 3 51679.8 12 || 34.5 10 95890 O9UKM9 RNA-binding protein Ray 34.70.6 8 || 345 O 984 12 MKi67 FHA domain-interacting Q9BYG3 nucleolar phosphoprotein 34393.3 9 34.5 1 O 367215 Q9Y30 thrNA-splicing ligase RtcB honolog 55723.7 14 || 34.5 O 891.33 cAMP-dependent protein kinase type P13861 -alpha regulatory subunit 45860.6 11 || 344 O 18060 Q01082 Spectrin beta chain, non-erythrocytic 260422. 64 || 34.4 10 49303 OO1780 Exosome component 10 10O339.3 20 || 343 O 17288 O75347 Tubulin-specific chaperone A 291.9 5 34.3 6 17007 P52292 importin subunit alpha- 582O42 11 || 34.2 O 87.747 MicroSomal glutathione S-transferase O A880 3 544.4 6 || 34.2 10 92892 Patent Application Publication Jul. 6, 2017. Sheet 56 of 141 US 2017/O192012 A1

FIG. 17 (cont'd) Cytochrome c oxidase assembly factor CR5.T3 6 homolog 152750 3 34.2 4. O BTB/POZ domain-containing protein C96CX2 KC12 35988.O 8 34.2 8 22554. Cat eye syndrome citical region Q9BXW7 protein 5 45325.6 7 34.1 O 33 182 P35222 Catenin beta- 751942 8 34.1 7 O NADH dehydrogenase ubiquinone P9821 favoprotein mitochondria 51027.0 2 34. 34645.5 CR96C36 Pyrroline-3-carboxylate reductase 2 3.39794. 10 3. O 68181. P467 60S ribosoma protein L5 3A590.8 11 34.O 10 96.395 Non-histone chromosoma protein PO514 HMG-4 O658.9 3 34.O 2 O Eukaryotic translation initiation factor 3 PS5884 subunit 8 96325.9 22 33.9 10 35687 C9POM6 Core histone macro-H2A.2 40288.4 1 33.9 10 79666 Pyrroline-5-carboxylate reductase 1, P32322 mitochondria 335,788 8 33.9 10 7A339 P6133 60S ribosomal protein L15 2O545.8 7 33.8 10 177342 O348 TAR DNA-binding protein 43 39983.9 33.8 1O 36170 P36776 Lon protease homolog, mitochondrial O7002.7 22 33.8 10 63614 Coiled-coil-helix-coiled-coil-helix domain-containing protein 2, C9Y6-1 nitochondria 15740.7 4. 33.8 2 O623 PO408O Cystatin-B 11196.6 2 33.7 5 41232 Bifunctional glutamate/proline--tRNA PO784 ligase 721879 41 33.6 10 54,482 Q8N F7 Nuclear pore complex protein Nup93 87 98.6 2) 33.6 10 54166 C75396 Vesicle-trafficking protein SEC22b 248215 8 33.5 10 59637 Bifunctional methylenetetrahydrofolate dehydrogenaseicyclohydrolase, P13995 mitochondrial 38068.2 9 33.4 10 1215315 C16576 Histone-binding protein RBBP7 50437.9 9 334 O 30977 Mitochondrial import inner membrane O4365 transiocase suit 44 51698. 17 33.4 10 78108 Q96EP5 DAZ-associated protein 42213.2 1O 33.3 10 85 127 P629 O 60S ribosonal protein 32 5973.9 5 33.3 1O 53869 Serine/threonine-protein phosphatase P67775 2A catalytic subunit alpha isoform 335O2.1 7 33.3 O 4943 P2494 Cyclin-dependent kinase 2 32098.3 8 33.3 8 O 39S ribosoma protein .22, C9NWU5 mitochondria 17427.6 6 33.3 9 O insulin-like growth factor 2 mRNA C9N8 binding protein 56324.3 16 33.3 10 4135 Alpha-aminoadipic semialdehyde PA949 dehydrogenase 52377.1 13 33.3 10 39249 O75390 Citrate synthase, mitochondrial 51940.7 13 33.3 1) 193641 Serinel threonine-protein phosphatase CR96HS1 PGAM5, mitochondria 30240.3 7 33.2 O 38630 CR14165 Malecti 324.050 8 33.2 4. O Transmembrane emp24 domain C9EWK6 containing protein 9 27.395 7 33.2 10 8614.6 P26373 60S ribosoma protein 13 2610.4 8 33.2 10 21794 HACA ribonucleoprotein complex Q9NY2 Sibirit 21762.2 6 33.2 O 576645 Patent Application Publication Jul. 6, 2017. Sheet 57 of 141 US 2017/0192012 A1

F.G. 17 (cont'd) P784O6 mRNA export factor 41595.5 9 33.2 9. 24285 Q04760 Lactoylglutathione lyase 2O138.5 6 33.1 1O 38664. Q9P258 Protein RCC2 56828. 3 33.1 1O 35.136 P2484A. Myosin regulatory Eight polypeptide 9 7734.7 5 33. 1O O Peptidyl-proly cis-trans isomerase-like C9Y3C6 1 835.9 5 331 A. 63.282 Peptidyl-prolyl cis-trans isomerase Q13526 NEMA-interacting 1 8357.4 4 33. 5 O Q86W42 HO complex subunit 6 homolog 35623.8 8 33.1 6 O RNA binding motif protein, X-linked C96E39 like- 4298.7 2 33.1 O O P62899 60S ribosomal protein L31 14363.5 4. 33.1 1. 12243 O9Y2BO Protein canopy honolog 2 209944. 5 330 3 O P08758 Annexin A5 35993.9 12 32.8 t O Pi4868 Aspartate-tRNA ligase, cytoplasmic 57535.5 15 32.7 1. 53280 CR9HAV7 GpE protein homolog 1, mitochondria 24507.2 6 32.7 10 7730 PO8753 Tropomyosin alpha-3 chain 3O421 1O 32.7 1. 26O79 Putative RNA-binding protein Lucif-like CR9Y383 2 4.8859.3 2 32.7 10 57078 Q13435 Splicing factor 38 subunit 2 1 OO341.8 21 32.6 10 156837 P62330 ADP-ribosylation factor 6 20196.3 S 32.6 3 O Nascent polypeptide-associated O3765 Complex Stubunit alpha 59224.4 9 32.6 10 1499 O P62753 40S ribosora Ofoter S6 28858 24,8743 OOOO59 Transcription factor A, mitochondria: 29324.8 O9Y3U8 60S ribosomal protein L36 t2310.8 4 32.4 10 43646 Coproporphyrinogen-i oxidase, P36551 mitochondria 5095.4 3 32.4 10 32901 Serine/threonine-protein phosphatase P62714 2A catalytic subunit beta isoforn 3645.4 7 32.4 O O PO7954 Fumarate hydratase, mitochondrial 52596.1 11 32.3 O 70460 Double-stranded RNA-specific P55265 adenosine deaminase 30272 25 32.3 O 49872 POG918 Carbonic anhydrase 2 29303. 6 32.3 O 66698 O75340 Programmed ceif death protein 6 21823.4 4. 32.3 O O High mobility group nucleosome P82970 binding domain-containing protein 5 3524.6 8 32.3 9 321.87 PAO925 Malate dehydrogenase, cytoplasmic 34.6O7.3 8 32.2 O 96.162 Q8Y81 pre-rrNA processing protein F SJ3 96.957.8 8 32.2 1O 898O4. Q14257 Reticulocabin-2 36933.5 8 32.2 1C 504.885 Cleavage and polyadenylation O438.09 specificity factor subunit 5 26284.3 6 32.2 10 183237 C9HOO6 5'-3' exoribonuclease 2 O5099. 9 32.2 O 58555 Mitochondrial import receptor subunit O94826 OM70 6839.3 S 32.1 10 46659 Synaptic vesicle membrane protein O99536 VA-1 homolog a248.5 32.1 O 56940 P50454. Serpin H 465,547 2 32.1 O 52623 UV excision repair protein RAD23 P54,727 honolog B 3996.7 7 32.1 O 37.425 P25787 Proteasome subunit alpha type-2 26O12.7 7 32.1 7 O Q9Y6C9 Mitochondrial carrier homolog 2 33.958.3 9 32.0 4. O Patent Application Publication Jul. 6, 2017. Sheet 58 of 141 US 2017/0192012 A1

FIG. 17 (cont'd) C4O11 Cold-inducible RNA-binding protein 18648.0 6 || 32O O 666 Ras GTPase-activating protein-binding CR 13283 protein 52224 9 || 32.O 9 74 12 Prolactin regulatory element-binding Q9-CU5 protein A6038.5 7 39 3. O PA6778 60S ribosomal protein L2 1862.9 5 39 O 978.78 P62O70 Ras-related protein R-Ras2 23627.7 5 39 1 O C8NWS 60S acidic ribosomat protein PO-like 34535.6 9 39 O O P8373 60S ribosomal protein 24 17893.0 39 O 88694 O92928 Putative Ras-related protein Rab-1C 22.245. 7 38 1O O P4O227 T-complex protein subunit Zeta 5612.8 13 38 O O3458 Dolichyl-diphosphooligosaccharide protein glycosyltransferase 48 kiba P39656 subt 50972.O 38 O O2223 PO8133 Annexin A6 74498.7 15 38 1.O. 5O15 Ubiquitin-like modifier-activating P2234 enzyme 1 18932.7 24 38 O O12O1 Multiple myeloma tumor-associated C9E36 protein 2 22O130 6 38 O Coiled-coil-helix-coiled-coil-helix domain-containing protein 3, OSNX63 mitochondrial 26437.5 || 8 || 31.7 || 0 | 7.1022 O 15523 ATP-dependent RNA helicase DOX3Y 7361CO 22 37 O O (J6 snRNA-associated Sm-like protein C9Y42O S4 1582O.8 3 37 4 O (Jbiquitin carboxy-terminal hydrolase C9YSKS isozyme 5 3414.3 7 || 37 8 O P397 Pastin-3 7324.4 4 36 O 53.72 Hydroxysteroid dehydrogenase-like QSYN6 protein 2 4585.7 2 36 O 387,555 TATA-binding protein-associated O928.04 actor 2N. 6922.0 11 || 36 O 96.25 P 19367 Hexokinase-1 O332 23 || 3.5 10 494.65 O 14818 Proteasone subunit apha type-7 24.1540 7 31.5 O 16496 O526C Surfeit locus protein 4 24418.2 4. 315 G 272O7 P82306 Small nuclear ribonucleoprotein F 9782.3 4. 34 6 83735 Q9BX3 Mitochondria dicarboxylate carrier 327O.2 7 34 O 35781 NADH dehydrogenase ubiquinone 1 O43678 alpha subcomplex subunit 2 O356 2 || 33 O O94905 Erin-2 29684.9 1O 31.3 O 701 18.47 C518.5 Prostaglandin E synthase 3 18982.6 5 33 10 109677 P3399 DNA replication licensing factor MCM4 97.28.4 9 32 O 5895O Q 14498 RNA-binding protein 39 5866.6 2 31 O O5869 Deoxyuridine 5'-triphosphate P33316 nucleotidohydrolase, mitochondrial 223838 7 31 O 2258 Phosphoenolpyruvate carboxykinase O16822 GTP, mitochondrial 60989. 15 31 O 49090 PA932 Nuclear autoantigenic sperm protein 803054 9 31 10 26508 Pas?6 60S ribosomal protein L27a 16675.5 5 311 O 2O3478 C6AA8 Ragulator complex protein LAMTOR 1858.9 4 311 6 26448 Sarcoplasmic/endoplasmic reticulum P-16615 caciun APase 2 112735.9 27 31 O 1.O. 10.5235 P8956 Small ubiquitin-related modifier 2 9548.2 3 31.O 10 26336 Patent Application Publication Jul. 6, 2017. Sheet 59 of 141 US 2017/O192012 A1

FIG. 17 (cont'd) CRO 1085 Nucleolysin TAR A2882.0 8 30.9 10 O C9 KX7 Nuclear pore complex protein Nup50 4892.7 2 30.9 O O SWSNF-related matrix-associated actin-dependent regulator of chromatin O6O264 subfamily. A member 5 122589.9 3O 30.9 O 69114 P54920 Alpha-solubie NSF attachment protein 33689.0 10 30.9 9 15858 CROO81 Splicing factor U2AF 35 kDa subunit 24622.3 6 30.8 O 66108 P39748 Flap endonuclease 1 4.2935.2 9 30.8 O 588 P. 388 DNA topoisonerase 2-alpha 7918.6 37 38 O 92672 P49.720 Proteasone subunit beta type-3 23234, 6 30.7 O 40O8.5 CO1 OS Protein SET 321949 7 30.7 10 212484 RNA-binding protein Musashi homolog CR96DH6 2 28130.4 7 30.7 O O Regulation of nuclear pre-mRNA Q9NOG5 domain-containing protein B 37O 138 1O 30.7 O O Transiocon-associated protein subunit P557 deta 191697 5 3.6 10 239676 G9Y4 Hypoxia up-regulated protein 1 1 11563.7 21 30.5 10 457.64 Eukaryotic translation initiation factor 2 PO598 subunit 1 363974 8 30.5 10 51603 O9 OAO N-acetyltransferase 10 116642.5 24 30.4 10 49278 CR92930 Ras-related protein Rab-8B 23755.2 5 30.4 O O P5858 Hepatoma-derived growth factor 2638.8 6 3O4. O O Phosphate carrier protein, COO325 ritochondria 4O483. 1 30.4 O 1828:8 CR 6643 Drebrin 7998.7 5 30.4. 10 57660 P49,736 DNA replication ficensing factor MCM2 102.580.6 2 30.3 10 70758 O9-3P7 Golgi resident protein GCP60 608786 30.3 7 28899 Acidic leucire-rich nucleaf O92688 phosphoprotein 32 family member B 257.03.3 5 30.3 10 42038 P3OO42 ES protein honolog, nitochondrial 27 178O 5 30.2 O O Aldehyde dehydrogenase X,

P3O837 rritochondria 57662.6 12 30.2 O 51849 inosine-5'-monophosphate P12268 dehydrogenase 2 56281.3 5 30.2 10 46440 Transmembrane emp24 domain P49,755 containing protein 10 25 A7. 7 30. 10 197397 O12874 Splicing factor 3A subunit 3 59 1912 15 30. O 9862 39S ribosomal protein 11, O9Y387 ?tochordia 19527.9 6 30. O O CRO4917 14-3-3 protein eta 28.389.9 7 30. O 40O2.92 P62847 40S ribosonal protein S24 96.76. 5 30.0 O 24,8277 J476. U5 tri-snRNP-associated O43290 protein 90.426.0 19 30. 9 18473 28S ribosomal protein S23, Q9Y39 mitochondria 2827.7 6 30.0 9 O Dihydroipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, P10515 mitochondria 6950.0 14 30. 10 967 CR98ZE4 Nucleolar GTP-binding protein 74363.9 19 30.8 10 43480 C9NP3 Acyl-coenzyme A thioesterase 13 137776 4 29.9 6 A637 28S ribosoma protein S21, P82921 Ochondria 10912.7 2 29.9 3. O Patent Application Publication Jul. 6, 2017. Sheet 60 of 141 US 2017/0192012 A1

FiG. 17 (cont'd) Pa. 1223 Protein BUD31 homolog 757.O.O. 5 29.9 3 O Myristoylated alanine-rich C-kinase P29966 Substrate 31725.8 29.8 1O 25889 2387 ONA topoisomerase 9. 182. 23 29.8 O 78990 P3O59 heme oxygenase 2 362040 9 29.8 1. 22773 39S ribosomal protein L50, O8N5N7 nitochondria 8498.1 S 29.8 2 O Q9BCGO Myb-binding protein A 5008O.5 32 29.7 1O 82468 P35579 Alyosin-9 1943.39.1 48 29.7 1) 76.17 Probable rRNA-processing protein O99848 EBP2 34909.O 29.7 O 43494 Acidic leucine-rich nuclear 39887 phosphoprotein 32 family member A 28699.5 7 29.7 10 7A 93 NADH dehydrogenase ubiquinone P1944 flavoprotein 2, mitochondria 27676.7 6 29.7 10 29325 39S ribosomal protein L54, O6P 161 riochondria 158762 3 29.7 1 8 Q356 Dynactin subunit 2 44622. 9 29.7 10 O O13573 SNW domain-containing protein 6.556 2 29.7 9 O C96-YS DDRGK domain-containing protein 1 35625.O. 5 29.6 5 O O9BUF5 Tour beta-6 chai 5033.5 10 29.6 10 67242,28 Sigma non-opioid intracellular receptor O9972 1 2263.5 5 29.6 8 O O9 NX4 WD repeat-containing protein 3 O71826 22 29.6 1O 24, 35 P 6949 Sathynin 862. 4 29.5 10 6509 P53582 Methionine aminopeptidase 1 44,127.7 7 29.5 3. O O15347 High mobility group protein B3 2315.1 8 29.5 O 993.49.5 Guanine nucleotide-binding protein P62879 G()|G(SGT) subunit beta-2 38072.5 10 294 10 47.427.61 C5RX3 Presequence protease, mitochondria 18529.0 2O 29.4 1O 23.796 ATP synthase subunit epsilon, P56381 nitochondria 5836.8 3 29.4 4 O ATP synthase subunit epsilon-like CR5VU8 protein, mitochondrial 5863.9 3 29.4 1 O ATP synthase mitochondrial F1 Q5C12 complex assembly factor 2935.6 7 29.4 8 8 Q92598 Heat shock protein 105 kia 94.6388 18 29.4 10 382O P25205 DNA replication scensing factor MCM3 96.08.3 19 29.3 10 52895 Peptidyl-prolyi cis-trans isomerase A O9Y536 like AB/C 18409.9 5 29.3 10 O CR8AA3 Proteasome subunit alpha type-7-ike 2682.47 5 29.3 1O 34497 28S ribosomal protein S17, CR9Y2R5 mitochondria 4616 3 29.2 4. 4001 O8NOY7 Probable phosphoglycerate mutase 4 28948.0 7 29. O O PS2191 26S protease regulatory subunit 4 49355.7 11 29.1 8 O NADH dehydrogenase ubiquinone O7538O iron-su'fur protein 6, mitochondria 4053.8 3 29.0 2 O O43660 Pleiotropic regulator 1 57084 12 29.0 8 O Mitochondrial import inner membrane Q32CO8 transiocase subart TM50 45426.2 9 28.9 O 73536 8579 tj2 sma: nuclear ribonucleoprotein B" 254.86.4 3 28.9 10 4O167 isochorismatase domain-containing O96AE3 protein 2, mitochondrial 20628.0 3 28.9 3 O Patent Application Publication Jul. 6, 2017. Sheet 61 of 141 US 2017/O192012 A1

FIG. 7 (cont'd) ATPase family AAA domain-containing Q9NW7 protein 3A 65349.6 17 28.8 10 89258 Heterogeneous nuclear CR1KMO3 ribonucleoprotein U-like protein 2 85675. 18 28.8 O 93.799 Eukaryotic translation initiation factor 3 P60228 Subunit E 5262O. 12 28.8 O 28937 Membrane-associated progesterone O1573 receptor component 2 23875.5 7 28.7 O 39827.8 Deoxynucleotidyltransferase termina CR5QE6 interacting protein 2 84868.3 8 28.7 10 23667 CR8WUD Ras-related protein Rab-2B 2A442.5 8 28.7 O O O16181 Septin-7 50915.6 11 28.7 O O Delta(3,5)-Delta(2,4)-dienoyl-CoA C1301 isomerase, initochondria 361584 9 28.7 10 57A71 Q8NCW5 NAD(P)H-hydrate epimerase 26337.8 3 28.7 6 O P54136 Aginine-tRNA ligase, cytoplasmic 7.972.7 7 28.6 10 4.1767 Q98O39 ATP-dependent RNA helicase DX50 83135.4 7 28.6 10 67O62.25

PSO866 40S ribosora orotein S2O 1831.7 5 28.8 O O24.4 Q98PW8 Protein NipSnap homolog 33481.1 6 28.5 O 3284.1 {Q9 G3 Prenylcysteine oxidase 57039.5 12 28.5 9 9569 NADH dehydrogenase ubiquinone 1 O9YSA9 beta subcomplex subunit 9 22O59. 5 28.5 3 O P1284 Apha-actinin- 104368.0 2O 28.5 10 18965 39S ribosomal protein 41, Q8XM3 mitochondria 15439.8 4 28.5 3 O 28S ribosomal protein S16, C9Y33 mitochondria 15573.0 4 28.5 1 O Vesicle-associated membrane protein P63O27 2 12719.8 3 28.5 8 71673 C925 Ras-related protein Rab-21 24746.8 8 28.4 6 30900 U6 snRNA-associated Sm-like protein Q9Y333 Sin2 1948.6 3 28.4 6 O P31 150 Rab GDP dissociation inhibitor alpha 520,1 9 28.4 5 4O635 PO7339 Cathepsir D 45065.5 1 28.4 10 38425.5 O15293 Reicocaihin- 38890.O. 9 28.4 7 O C924.99 ATP-dependent RNA helicase OOX1 834.17 6 28.4 O 40528 P4972 Proteasome subunit beta type-2 2307.4 y 28.4 9 4.05016 DNA-directed RNA polymerase if P 19387 Subit RPB3 317834. 5 28.4 3 17223 28S ribosomal protein S18b, O9Y676 nitochondria 29737.8 8 28.3 4. O P62841 40S ribosomal protein S15 704O2 3 28.3 O 46.36 Putative heat shock protein HSP 90 O4568 alpha A2 394789 8 28.3 O O 86Y82 Syntaxin-12 3756.0 7 283 9 29398.5 Ribosomal RNA processing protein 1 Q14684 homolog B 836,725 19 28.2 O 524.62 Q8 WSO PhD finger protein 6 39.393.4 9 28.2 8 O Q838 Alaine aminotransferase 2 53213.3 9 28. 2 O U4/U6 small nuclear ribonucleoprotein O43172 Prp4. 59089.5 11 28.8 O 28.365 OOO629 importin subunit alpha-3 584OO. 9 28.0 9 O P6285 40S ribosonia protein S25 137992 4. 28.0 O 184648.5 Patent Application Publication Jul. 6, 2017. Sheet 62 of 141 US 2017/O192012 A1

FIG. 17 (cont'd) O 14.737 Programmed ceil death protein 5 14285.1 4. 28O 7 O C8WXF Paraspeckie component 1 52.299.9 O 28.0 O 69666 Q13868 Exosome complex component RRP4 33017.2 7 28.0 7 1820 P3689 DnaJ homolog subfamily A member 45609.6 7 28.0 10 5703.5 P4265 3-ketoacyl-CoA thiolase, mitochondrial 42380.4 7 28.0 f O Proteasome activator complex subunit PS289 3 30339.0 7 28.0 1C 14709 Q86UP2 Kinectin 52364.9 27 27.9 10 36339 C9E3W 5 Splicing factor 3B subunit 5 O249,4 2 27.9 1 O O004.8 importin-5 236434 2 27.9 O 43.738 P6840 Casein kinase 8 subunit alpha 4100. O 27.9 O 42.74. Eukaryotic translation initiation factor O 14602 A Y-chromosomal 18556.4 3 278 9 O Structural maintenance of Q9CE chromosomes protein 3 A 1941 29 27.8 10 34.577 C93YX7 Putative beta-actin-like protein 3 423585 7 27.7 1. O P1643 ristore 1.2 2.364.8 8 27.7 O 3343983 P54,652 Heat shock-related 70 kDa protein 2 703O8.2 16 27.7 O 9245.247 PO9012 U1 small nuclear ribonucleoprotein A 3279.6 6 27.7 1O 96672 P6163 Alpha-centractin 42729 10 | 27.7 8 O P1227 Nucleoprotein TPR 2676923 49 27.6 1. 765 Putative heat shock protein HSP 90 Q58FF8 beta 2 4452O1 12 27.6 1C O NADH dehydrogenase ubiquinone Q9BU6 alpha subcomplex assembly factor 3 1952.2 4. 27.6 5 O Zinc phosphodiesterase EAC protein C98C52 2 778847 13 27.5 O O ATP synthase subunit gamma, P36542 fitochondria 3.29956 8 27.5 10 137214 P43686 26S protease regulatory subunit 6B 45765.6 7 27.5 O O Sorting and assembly machinery Q9Y512 component 50 homolog 52375.4 9 27.5 6 O Dihydrolipoyl dehydrogenase, PO9622 mitochondria 54747.6 13 27.5 10 17737 28S ribosomal protein S22, P82658 nitochondria 445.5 8 27.5 9 40224 P13929 Beta-encase 44792.2 8 27.4 10 9493 Q562R1 Beta-actin-like protein 2 42345.5 12 27.4 10 O OO 518 Adenylyl cyciase-associated protein 52322.2 O 27.4 1. A634 CO2880 DNA topoisomerase 2-beta 839346 36 27.3 O 62574 Structura mainterance of C14683 chronosomes protein 1A 4386O4 28 27.3 10 51345 DNA-directed RNA polymerases , EI, P52434. and Sloit RPABC3 172OO4 4. 273 3 O G8XM2 Chromatin complexes subunit BAP18 1639.4 3 27.3 10 O CR 1323 Protein Red 65718.4 12 273 1O 3644 PA9327 Fatty acid synthase 276.050.2 50 27.3 O 50733 P58134 ATP synthase subuniti, mitochondrial 10728. 3 27.3 O 174952.5 ER membrane protein complex C15OO6 Subunit 2 3504.7 6 23 8 2346.5 P5370 Cytochrome c-type heme lyase 3000.8 6 27.2 9 29826 C9H307 Pi 74423.7 A 27.2 10 59465 Patent Application Publication Jul. 6, 2017. Sheet 63 of 141 US 2017/0192012 A1

FIG. 17 (cont'd) O751.31 Copine-3 60986. 1 27.2 9 32256 P55060 Exportin-2 84.488. 2 27.2 1O 709 P356O6 Coatomer subunit beta' O3342.8 9 27.2 10 29484 Putative coiled-coil-helix-coiled-coil helix domain-containing protein O5:15 CHCHO2P9, mitochondrial 1577.7 2 27.2 2 O 39S ribosomal protein L45, Q9BR2 mitochondria 35636. 5 27. O 39S ribosomal protein L44, Q992 ritochondria 37877.6 9 27. 9 17676 Secretory carrier-associated O4828 membrane protein 3 37657.8 6 27.1 9 26598 Cytochrome c1, heme protein, P88574. ritochondria 357.642 6 27. 10 25855.5 P78347 General transcription factor - 1107O6.5 20 27, 1 O 45.425 ATPase family AAA domain-containing Q5:2N8 protein 3C A66648 8 27.0 1O O Q9UDW Cytochrome b-c complex subunit 9 73O8.5 2 270 9 52728 Histone acetyltransferase type B O 4929 catalytic subunit A6459. 9 270 1. 58136 Putative heat shock protein HSP 90 O58FF7 beta-3 688.67. 19 27.0 10 O P53396 ATP-citrate synthase 121218.3 25 270 1O 66554 NAD-dependent malic enzyme, P23368 ritochondria 60400. 3 26.9 1O 5,786 O9625 Splicing factor 45 4589.7 26.9 O 19077 P2O34.O Ras-related protein Rab-6A 2O7210 4. 26.9 10 275880 O4566 DNA replication licensing factor MCM6 93.858.9 21 26.9 10 43933 PO6744 Glucose-6-phosphate isomerase 63992.6 1 26.9 1C 77.025 Transmembrane emp24 domain Q727H5 containing protein 4 23759.4 5 269 10 672O 39S ribosomal protein L46, O9H2W6 mitochondria 31892 8 26.9 4. O PO7741 Adenine phosphoribosyltransferase 1857.2 A 26.9 3 O PS2491 Ras-related protein Rab-1 1A 24.5076 7 26.9 1O 75693 39S ribosomal protein L21, OF22W9 mitochondria 22985.8 4 26.8 1 O PA5973 Chromobox protein homolog 5 22396. 5 26.7 1O O Rho-related GTP-binding protein P84095 RhoG 21764.7 3 26.7 f O PaS783 40S ribosomal protein SO 18897.8 6 26.7 O 18362 P35659 Protein DEK 4O974.7 28.7 10 161739 O9Y266 Nuclear migration protein nudC 383.00.0 8 26.6 6 O O498O Nuclear mitotic apparatus protein 1 22022.3 46 26.6 10 27.256 Mitochondrial import inner membrane O9Y59 translocase subunit im8B 957.7 2 265 5 O Replication protein. A 70 kDa DNA P27694 binding subunit 68.765.6 4 28.5 O 42578 O9252O Protein FAM3C 24965.7 6 264 2 O CO9028 Histone-binding protein RBBPA A6505.4 9 26.4. 10 196683 PS3621 Coatomer subunit alpha 140403.3 25 26.3 O 3461 O95573 long-chain-fatty-acid-CoA ligase 3 81389.7 5 28.3 O 46.386 O724W -xylulose reductase 2698.2 5 26.2 2 O Patent Application Publication Jul. 6, 2017. Sheet 64 of 141 US 2017/0192012 A1

FIG. 7 (cont'd) Transloco-associated protein subunit P43307 alpha 30952.4 4 28.2 1C 97239 P49756 RNA-binding protein 25 598062 9 26.2 10 3478 NADH dehydrogenase ubiquinone: 1 O980OO beta subcomplex subunit 30 2O619 6 26.2 9 O O75475 PC4 and SFRS-interacting protein A8534.6 26.1 O A805 O969 Actin-like protein 6A 458.33.5 9 28. O O P62854. 40S ribosomal protein S26 3300.6 3 28.1 10 2.548A. Regulation of nuclear pre-mRNA C966 domain-containing protein A 33929.0 S 28. O 476O O43776 Asparagine-tRNA tigase, cytoplasmic 63798.4 3 28.1 10 175O2 Succinyl-CoA ligase ADP-forming O9P2R7 subunit beta, mitochondria 49520.8 26. O 34069 26S proteasome non-ATPase (9 JNVS regulatory subunit 13 A3257.7 O 28, O 7143.5 Protein transport protein Sec61 P80468 subunit beta OO315 2 26.0 3 O Ubiquitin Carboxyl-terminal hydrolase PO9936 isozyme L1 25166.6 6 28.0 6 O C5J5XO Complex is assembly factor LYRM7 12O119 3 26.0 3 3503 Succinyl-CoA:3-ketoacid coenzyme A P55.809 transferase 1, mitochondria 566140 9 28. 1 O 7587 26S proteasome non-ATPase Q15008 regulatory subunit 6 45816.6 O 28.0 6 O Dehydrogenasefireductase SR family C9Y394 member 7 35853.9 5 28.0 4. O Eukaryotic translation initiation factor 3 (7.2H7 Sibunit V A29592 7 25.9 8 10050 CDGSH iron-sulfur domain-containing C9NZA5 protein 123O2 2 25.9 5 O P3558) Myosin-10 238885 40 25.9 O 69769 P61158 Actin-related protein 3 47827.5 8 25.8 10 O CR92522 Histore X 2248f.1 6 25.8 10 34349 28S ribosoma protein S31, CR92665 nitochondria 45432.6 O 25.8 O 47217 PO904. Gamma-enolase 47610.8 8 25.8 O O Ribose-phosphate pyrophosphokinase P60891 1 35347.5 6 25.8 O 17606 PA 1252 isoeucine-tRNA gase, cytoplasmic 4580.8 26 25.8 || 0 S1312 P477.56 F-actin-capping protein subunit beta 33O3.3 8 25. 1O O C2TAY7 WD40 repeat-containing protein SMU 5817.3 O 25.7 O 4734 39S ribosomal protein 40, Q9NC.50 mitochondria 24490.4 4 25. 4. O O75477 Erin-1 39C970 8 25.7 O 36504,3 Wesicle-associated membrane protein P51809 7 260889 S 25.7 8 O A9257 Protein ERGIC-53 578342 7 25.7 f O O9P25 Leucire-tRNA ligase, cytoplasmic 135664. 25 25.7 1. 43487 Q15005 Signal peptidase complex subunit 2 25288.0 5 25.7 9 66; 77 6088 Ubiquitin-conjugating enzyme E2 N 17949 4 25. 2 O Putative ATP-dependent RNA Q72E3 helicase DHX3. 134905 26 25.6 O 29799 Putative high mobility group protein B2RPKO Bike 24409.1 7 25.6 1. 2O8458 Patent Application Publication Jul. 6, 2017. Sheet 65 of 141 US 2017/0192012 A1

FIG. 7 (cont'd) P253.25 3-fnercaptopyruvate sulfur transferase 33463.6 4. 25.6 3 O P21333 Fari-A 2836.2 43 || 25.6 O 55.298 Caseinolytic peptidase B protein C9HO78 honolog 758504 5 25.6 O 4289 O1498 Exportin-1 24526.7 25 25.5 1. 50473 P4959 Serie-tRNA ligase, cytoplasmic 59290.6 3 || 25.5 7 O Coited-coil domain-containing protein C98A33 47 55995.2 9 || 25.4 1O 484.35 C98W4. Nucleolar complex protein 4 homolog 588.67.0 2 25.4 7 24508.5 26S proteasome non-ATPase OOO23 regulatory subunit 477845 9 || 25.4 10 8209 Ribosome biogenesis regulatory C 1558 protein homolog A 1250.4 1 25.2 O 4.9358 C92769 Histone deacetylase 2 559346 O 25.2 10 85875 P33993 DNA replication licensing factor MCM7 63955.8 15 || 25.2 10 277O6 Celi division control protein 42 P60953 honolog 2600.8 3 25. 1 O 5153 Ras-related protein Rab-13 230O2.3 6 25.1 10 2257475 Cleavage and polyadenylation Q8N684. specificity factor subunit 7 53325.8 O || 25. O 28998 O 14137 Ribosone biogenesis protein BOP 84314.) 4 25. O 10242 C14320 Protein FAM50A 4O247 6 25.1 7 8433 P6421 V-type proton ATPase subunit d 4O7854 7 25.1 2 O KH domain-containing, RNA-binding, signal transduction-associated protein CRO7668 461526 O || 25.1 1. 3.4272O NADH dehydrogenase ubiquinone O753O8 iron-sulfur protein 2, mitochondria 52945. O || 25.1 10 3O690 Q16695 Histore 3. 15622.3 6 || 25.0 10 554896 CR 13243 Serinefarginine-rich splicing factor 5 27 07.0 7 25.0 O 76208

P633 CD81 antigen 26493.8 5 25.0 2 O P623O8 Small nuclear ribonucleoprotein G 8553.1 2 25.0 1. O P68431 Histore 3. 15518.2 6 25.0 O O Esocitrate dehydrogenase NAD P51553 subunit gamma, mitochondria 4393.6 8 24.9 6 O Adipocyte plasma membrane Q9HDC9 associated protein 39A633 9 || 249 10. 3.4986 Calcium-binding mitochondrial carrier CSNK1 protein SCaMC-1 52554.O 11 24.9 18 53805 Probable ATP-dependent RNA Q96GCR7 helicase DDX27 90.348.7 9 24.9 35638 PO2786 Transferrin receptor protein 85327.7 8 || 24.9 O 22629 C8N183 Mimitin, mitochondria 19856.4 3 24.9 5. O Eukaryotic translation initiation factor Q9GZV4. SA-2 17135.4 5 24.8 O P51572 B-cell receptor-associated protein 31 3.486.0 8 24.8 O 84.38 C13247 Seriefarginine-rich spicing factor 6 34.804.6 9 || 24.8 O 344-39 Sodium/potassium-transporting P13637 ATPase subunit alpha-3 131744 9 24.8 1. 85064. O3ZCM7 Tubulin beta-8 chair 502894. 2 24.8 O 236215.7 C8WAO WD repeat-containing protein 75 9.59816 17 24.7 8 O POO403 Cytochrome c oxidase subunit 2 25.36.2 5 24.7 1O 17927 P 1042 Histore has 21865.3 9 24.7 1. A346.096 Patent Application Publication Jul. 6, 2017. Sheet 66 of 141 US 2017/0192012 A1

FIG. 7 (cont'd) P2744 Adenylate kinase 4, mitochondrial 25.382 6 24.7 Monofunctional C1-tetrahydrofolate CR6UB35 synthase, mitochondrial 98.644.O 9 24.6 10 A717 Phosphatidylethanolamine-binding P30086 protein 21170.9 4 24.8 6 O DnaJ homolog subfamily B member O9BS4 1 4O799.1 8 || 246 9 O NADH dehydrogenase ubiquinone 1 C9PO32 alpha subcomplex assembly factor 4 20323.5 5 24.6 O Mitochondrial-processing peptidase O754:39 Subit beta 55107.6 9 245 10 27052 PO9234 U smal nuclear ribonucleoprotein C 17564.9 3 245 10 151770 Cytochrome b-c Complex subunit P47985 Rieske, mitochondria: 29953.2 6 24.5 O 95.277 Guanine nucleotide-binding protein Q9-AWO subunit beta-4 383O8.6 9 24.4 O O P505O2 Hsc70-interacting protein 45O2.9 8 24.4 10 17245 Guanine nucleotide-binding protein Q9BVP2 iike 3 678.1 24.4 O O Q9NUP9 Protein in-7 honolog C 2948.1 4. 24.4 3 8 CR 15637 Splicing factor : 67657.2 iO 24.3 10 73722 O9GZS3 WD repeat-containing protein 6 33,751.7 6 || 24.3 2 O Heterogeneous nuclear Q9BU2 ribonucleoprotein U-Bike protein 89.372.8 9 243 10 50917 Heterogeneous nuclear O6812 ribonucleoprotein C-like 3299.5 8 || 24.2 10 1481.70 O9YAW2 Ribosoma biogenesis protein LAS1t 69795.8 3 24. O 28722 39S ribosomal protein L24, C96A35 mitochondria 25O28.9 4. 24.1 8 13668 P5990 Ras-related protein Rab-35 242O.9 5 24. 10 149943 Glutamate dehydrogenase 2, PA 9448 intochondria 6776.3 5 24.0 O CR9 JBEO SUMO-activating enzyme subunit 36O895 6 24.O. 5 O CR96CO Protein FAM138A 1654.5 4. 23.9 2 O Q8C 2 Retino dehydrogenase 35509.O 6 23.9 10 30924 Nuclear pore membrane glycoprotein Q8EM1 2 6689.3 8 23.9 1O 7808 P2O338 Ras-related protein Rab-4A 246748 5 23.9 1. O NADH dehydrogenase ubiquinone) 1 P597O alpha subcomplex subunit 8 20561.3 5 23.8 3 O NADH dehydrogenase ubiquinone OOO27 iron-sulfur protein 8, mitochondrial 2428.4 6 23.8 10 453O3 28S ribosomal protein S29, P5398 mitochondria 43103.6 8 23.8 O 3305 Q16543 Hsp90 co-chaperone Codc37 4498.6 8 23.8 9 O U6 snRNA-associated Sm-like protein P62312 SS 91846 4 || 23.8 2 O p15311 Ezrir 695270 6 || 23.7 1G 6852 PO7305 -Store O 2005.O 4. 23.7 10 96846 CR86E4. Protein, YRC 63894.1 3 || 23.7 O O BAG family molecular chaperone O9586 regulator 2 23943. 4. 23.7 4. O Cancer-related nucleoside O9BSD7 triphosphatase 20.9412 3 23.7 3 29409 O9Y3EO6 Mitochondrial fission 1 protein 169948 3 23.7 2 O Patent Application Publication Jul. 6, 2017. Sheet 67 of 141 US 2017/0192012 A1

F.G. 7 (cont'd) P697 Nuclear transport factor 2 14649.6 3. 23.6 7 O NADH dehydrogenase ubiquinone O9POO alpha subcomplex subunit 3 6698.4 3 23.6 8 O Chromodomain-helicase-DNA-binding O 14839 protein 4 220994.9 33 23.6 O 5443.5 Q6)K1 60S ribosoma protein L7-like 28775. 4 23.8 4. 5454.5 O86YS6 Ras-related protein Rab–43 235675 4. 23.6 10 26899 PO910 3-ketoacyl-CoA thiolase, peroxisomal 40558.2 23.6 9 O hioedoxin-related transmenofare C9H3N protein 3290.5 7 23.6 O 91.884 P26038 Moesin 67934.2 14 23.6 10 O O75369 Fiami-B 266O73.9 47 23.6 10 2.942 P42696 RNA-binding protein 34 3785. 9 23.8 6 O C-1-tetrahydrofolate synthase, P1 586 cytoplasmic 12243.7 18 23.5 10 58899 O9H7B2 Ribosome production factor 2 homolog 35754.O. 6 23.5 1O 3O4 Mycophenoic acid acyl-glucuroide O9NU esterase, mitochondria: 34274.7 7 23.5 10 23.559 39S ribosoma protein 49, O1345 mitochondria 19255. 5 23.5 9 O Dolicho-phosphate O6O762 mannosyltransferase 29691.3 7 23.5 10 27669 ATPase family AAA domain-containing CR59A4 protein 38 59423.7 15 23.5 1O 34.33 O9NSE4 isoleucine-tRNA ligase, mitochondrial 1 A7612 17 23.4 10 580.40 tubulin beta-8 chain-like protein A6NNZ2 OC260334 50200. 8 23.4 O O Putative pre-mRNA-splicing factor O4343 ATP-dependent RNA helicase DHX5 91734 16 23.4 10 787.64 transmembrane emp24 domain CR9Y3B3 containing protein 7 23544.5 4. 23.4 8 O 28S ribosomal protein S0, P82664 mitochondria 23 13.6 4. 23.4 2 O Wesicular integral-membrane protein O12907 VP36 4.0570.9 8 23.3 O 21705 Putative eukaryotic translation O2WR3 initiation factor 2 subunit 3-ike protein 51525, 8 23.3 O O P35221 Catenin alpha-1 102018.2 8 23.3 O 2313.5 26S proteasome non-ATPase O 13200 regulatory subunit 2 10094.3 17 23.2 O 22029 O992E9 Ribosome-binding protein 138163.6 19 23.2 10 25298 P13489 Ribonucease inhibitor 51798.4. 8 23.2 2 O Enoyl-CoA deita isomerase 1, P42126 mitochondria: 321 2.5 6 23.2 O 1542765 P33992 DNA replication licensing factor MCM5 83O84. 13 23.2 10 37949 P4874 Putative heat shock 70 kDa protein 7 4.0472.6 8 23.2 1O O POCG47 Polyubiquitin-B 25818.7 6 23, O O P 19784 Casein kinase subunit alpha' 4384.4 7 23. 8 O P35249 Replication factor C subunit 4 4.01.95. 7 23.1 6 O RNA-binding protein with serine-rich O15287 donain 32090.6 6 23. O 5624 C15046 Lysine-tRNA Bigase 70228.9 23. 1O 33O2 C13895 Bystin 49.829.5 10 23. 3 O79 O8WXX5 DnaJ honolog subfamily C member 9 3008.O.9 6 23. 6 O Patent Application Publication Jul. 6, 2017. Sheet 68 of 141 US 2017/0192012 A1

FIG. 17 (cont'd) CR9 JFNO Protein NipSnap honolog 3A 28580.7 s 23. 5 O Eukaryotic translation initiation factor 3 CR9Y282 subunit - 64OOO 9 23.1 10 41950.5 PO768 S-formylglutathione hydrolase 31976. 4. 23. 2 O Ubiquinol-cytochrome-c reductase O9BRT2 complex assembly factor 2 149889 3 230 1 O PO7108 Acyl-CoA-binding protein 12645 23.0 5 O 28S ribosomal protein S28, O9Y2C9 nitochondria 2013. 3 230 4. O (9 JNP9 Peptidyl-poly cis-trans isomerase E 335148 7 230 6 Histone deacetylase complex subunit OOO422 SAP 8 1768. 5 22.9 1 O Ras GTPase-activating-like protein PA6940 QGAP1 189879.6 30 22.9 10 A2002 Glyoxylate reductase/hydroxypyruvate OSJBO7 reductase 360675 7 22.9 6 O P35837 RNA-binding protein FUS 53618.5 1 22.9 1O 26940 Ribosome-recycling factor, C96E1 raitochondria 2529.3 5 22.9 3 O P.11233 Ras-related protein Ral-A 23737.9 22.8 3. O Cleavage and polyadenylation CR 663.O specificity factor subunit 6 58508.7 8 228 10 62313 CR9 UNX3 60S ribosomal protein 26-like 1 17256.3 5 228 10 177648 P6254 60S ribosomal protein 26 172582 5 22.8 10 O Pre-mRNA 3’-end-processing factor Q6JN 15 rip 1 57965.9 S 22.8 10 A8495 P18077 60S ribosomal protein .35a 12594.7 5 227 7 106428 CR3642 Four and a half LEM domains protein 342O3 6 22.7 6 O5024 Exosome complex Cornponent RRP42 32448,8 5 22. 2 O Methylcrotonoyl-CoA carboxylase beta Q9CCO chain, mitochondria: 599.10.8 9 22. 18 O Q09181 Nuclear cap-binding protein subunit 92923, 14 22.7 10 O Probable ATP-dependent RNA Q9-OS4 helicase ODX47 A6785.8 O 22.6 10 50778 Q 6531 DNA damage-binding protein 1 128222.7 22 226 10 28858 PS1923 Coatomer subunit zeta- 20255.3 5 22.6 3 O 2 snRNP-associated StrP notif OSO42 containing protein O429.9 16 22.6 10 1205 O9JA4 Ragulator complex protein LAMTOR3 13679.8 228 1 O Superoxide dismutase win, PO4179 mitochondria 22944.9 7 22.5 10 94.060.5 Aspartate aminotransferase, P1774 cytoplasmic 48475.7 11 22.5 2 Q330 Polyadenylate-binding protein 4 71227 4 22.5 10 28978 Q8ZP2 Putative protein FAM10A4 27577.9 A 22.5 10 POO491 Purine nucleoside phosphorylase 32348. 7 22.5 6 O Pa 1250 Glycine-tRNA ligase 83807. 15 225 10 38355 Putative RNA-binding protein illuct-like O9NO29 4657.5 8 22.5 10 O P235.26 Adenosylhomocysteinase A6838.2 8 22.5 10 53963 O94906 Pre-mRNA-processing factor 6 105475.5 2 224 1O 3O945 NADH dehydrogenase ubiquinone: 1 O678 alpha subcomplex subunit 5 1355.7 2 22.4 2 O Patent Application Publication Jul. 6, 2017. Sheet 69 of 141 US 2017/0192012 A1

FIG. 17 (cont'd) O5758 Neutra amino acid transporter B(0) 57.0546 9 22.4 10 17949.5 ER membrane protein complex O902 Subunit 3 27433.8 3 22.4 2 O O5289 Periodic tryptophan protein 2 honolog 1034217 8 22.3 10 32629 39S ribosomal protein 15, O905 mitochondria 33590.9 7 22.3 6 O NADH dehydrogenase ubiquinonel 1 alpha subcomplex subunit 10, O95299 mitochondria 4,192.8 22.3 9 O Q13547 Histone deacetylase 1 55673.4 10 22.2 O 3419 Eukaryotic peptide chain release P62495 factor subunit 1 49259. 10 22.2 4 O QO 130 Serinefarginine-rich splicing factor 2 25476.4 6 22.2 10 181072.5 PO5787 Keratin, type 3 cytoskeleta 8 55.56.4 S 22.2 10 8O145 Ribosomal RNA-processing protein 7 Q9Y3A4 homolog A 325052 4 22.1 1 O O9-8-O Nucleolar protein 11 82093.2 1 22.1 9 12603 26S proteasome non-ATPase O43242 regulatory subunit 3 60917 2 22. O 4950 2,4-dienoyl-CoA reductase, O6698 mitochondria 363.529 7 22.1 5 O j4f 6.5 tri-Snr-P-associated O53GSS protein 2 59.7592 3 22, 10 19152 Putative ATP-dependent Clp protease O16740 proteolytic subunit, mitochondria 3O465.3 6 22.0 8 6584 3-hydroxyisobutyrate dehydrogenase, P3937 mitochondria 35728.2 7 22.0 7 O 28S ribosomal protein S9, P82933 mitochondria 43063.O 8 22.O 10 3455 Serrate RNA effector nolecule O98XP5 homolog 18066.O 15 219 1 O 62339 insulin-like growth factor 2 mRNA OOO425 binding protein 3 A3550.3 219 10 22.3289 Putative ribosoma ra P46087 methyltransferase NOP2 85.5582 4 219 10 8CO35 Mitochondrial-processing peptidase O10713 subunit alpha 58766.3 10 21.9 9 O O9NY 9 ropomodulin-3 39765.9 6 21.9 O PO6454. Prothymosin alpha 12138.4 3 28 4. O P565.45 C-terminal-binding protein 2 8.5776 10 218 10 6O744 O 5400 Syntaxin-7 28722. 7 21.8 4 O NADH dehydrogenase ubiquinone 1 alpha subcomplex subunit 9, O6795 mitochondria A268O 6 21.8 9 23.386.5 Probabie ATP-dependent RNA OO14 helicase DDX46 17875.5 23 21.7 1. 34.293 O98W92 threonine-tRNA ligase, mitochondria 88916 3 21.7 7 O Cysteine and histidine-rich domain O9. containing protein 38288.2 5 21.7 O P22090 40S ribosomal protein S4, Y isoform 296838 7 21.7 10 O O96EE3 Nucleoporin SEH1 A36553 7 21.7 10 O Smal: nuclear ribonucleoprotein P 14678 associated proteins B and B' 26385.7 5 21.7 10 O O92843 BC-2-like protein 2 37399.0 7 216 10 7OO83 P17066 Heat shock (0 kDa protein 6 7484.5 14 218 10 3.2898 Patent Application Publication Jul. 6, 2017. Sheet 70 of 141 US 2017/O192012 A1

FIG. 7 (cont'd) C997.33 Nucleosome assembly protein 1-like 4 42994.6 6 21.6 7 O Q9Y224 Tyrosine-tRNA ligase, mitochondria 53427.2 O 216 6 O PO9496 Clathrin fight chain. A 25,166.2 4 21.6 10 O Tricarboxylate transport protein, P53OO7 mitochondrial 34.3549 7 215 O 418.4 Asparagine synthetase glutamine PO8243 hydrolyzing 61379. 11 215 10 3.9906 P57088 Transmembrane protein 33 28320,4 A. 215 10 73242 socitrate dehydrogenase NADP), P48735 mitochondrial 5,365.6 9 21.5 10 O O6076 Catenin deta- 92842. 17 215 10 6O72 O60508 Pre-mRNA-processing factor 7 66285.7 9 24 2 O Glutaminase kidney isoform, O94925 nitochondrial 66788, O 214 t 28596 P25788 Proteasome suburnitalpha type-3 28288.4 6 214 1C O ER membrane protein complex CR58M3 subunit 4 17439.6 2 23 3 O P42285 Superkiller viraticidic activity 2-like 2 8.835 7 213 10 35624 CR9NQ55 Suppressor of SWI4 it homolog 52832.4 6 23 O O 5'-nucleotidase domain-containing Q9-857 protein 2 54.852.5 9 23 10 O O43681 APase ASNA1 39249. 5 21.3 8 O and apoptosis regulator O8N63 protein 2 103649.7 4 21.2 10 39.390 O95758 Polypyrimidine tract-binding protein 3 5893.3 6 21.2 O O 39S ribosomat protein ,

CR98YD6 mitochondrial 37 136.9 6 2.2 10 O Cleavage and polyadenylation CR9P20 specificity factor subunit 2 89342.3 34 21.2 4. O Serinefarginine repetitive matrix CB9C35 protein 2 214O66.1 24 212 O 54522 P1512 Aidose reductase 362526 6 21.2 9 O O 14108 Lysosome renbrane protein 2 47685.3 6 212 7 O Sec family domain-containing protein Q8WWM8 1 72722.2 O 21.2 9 22102.5 26S proteasome non-ATPase Q9946O regulatory subunit 105(45.4 9 21.2 10 23028 Q9BS8 Extended synaptotagnin-1 23943.O. 18 21. 10 31281 Q9BRX8 Redox-regulatory protein FAM213A 25227.5 5 21.1 6 O Q92575 UBX domain-containing protein 4 57O62.7 6 21, 3 O Phenylalanie-tRNA ligase alpha O9Y285 Subunit 57620,8 O 21. 5 O C6RF-5 WD repeat-containing protein 74 4886.2 6 210 4. O Glutaredoxin-related protein 5, Q86SX6 nitochondria 167419 3 210 9 266.79 Glycerophosphodiester phosphodiesterase domain-containing Q8N97 protein 35043. 6 210 8 P1 O155 60 kDa SS-A/Ro ribonucleoprotein 57679.2 9 210 1O O O9NR28 Diablo homolog, mitochondrial 237814 4 2.0 1. 5083 Putative heat shock protein HSP 90 CR58FGO alpha A5 3898.62 8 2O 10 O ATP-binding cassette sub-family D P28288 member 3 68.192 11 21.O 10 6093 Patent Application Publication Jul. 6, 2017. Sheet 71 of 141 US 2017/0192012 A1

FIG. 17 (cont'd) PSO914 60S ribosomal protein 14 23545.9 4. 20.9 10 257359 Apoptotic chromatin condensation O9xW3 inducer in the nucleus 1976.4 20 20.9 10 77856 C9Y2S7 Polymerase delta-interacting protein 2 42264 8 20.9 7 O RNA 3'-terminal phosphate cyclase Q9Y2P8 like protein 41298.9 6 20.9 5 3677 Ch92973 Transportin- 1316525 5 20.9 O 52434. PO9972 Fructose-bisphosphate aldolase C 39855.1 9 20.9 10 O P5772 Poly(rC}-binding protein 3 38266.4 7 20.9 10 O Probabie ribosome biogenesis protein CR9 JHA3 R224. 19906.3 4. 20.9 5 O Short-branched chain specific acyl P45954 CoA dehydrogenase, mitochondrial 47827.7 8 20.8 4. O Sma: nuclear ribonucleoprotein P63 62 associated protein N 2A7852 5 20.8 3 O HLA class histocompatibility antiger, PO1892 A-2 alpha chain 4, 27. 6 20.8 9 O HLA class histoCompatibility antigen. P10316 A-69 alpha chain 41282.O 6 20.8 9 O P8388 60S ribosomal protein 36a 2726.O 2 2.8 O 101103 CR969CO 60S ribosonal protein 36a-ike 12754.O 2 20.8 10 O P 5927 Replication protein A 32 kDa subunit 3287.6 A. 20.7 O O Rho-related GTP-binding protein PO834 Rho 22348.6 5 20.7 O O PAO429 60S ribosomal protein 13a 236343 5 20.7 10 2848 P4O937 Replication factor C subunit 5 375859 11 20.7 6 O CZ384 Nucleoporin p54 443647 6 20.6 6 O Exosome complex exonuclease OSY2 RRP44 1083O34. 14 20.8 10 26400 Dihydrolipoyllysine-residue succinyltransferase component of 2 oxoglutarate dehydrogenase complex, P38957 nitochondria 49097.6 9 2.5 10 78517 C688 Atastin-3 60998.3 O 20.5 1 O Q92734 Protei TFG 3505.0 5 20.5 O 4-trimethylaminobutyraldehyde P4989 dehydrogenase 54745 O 20.5 O 20982 2',3'-cyclic-nucleotide 3'- PO9.543 phosphodiesterase 4673.79 O 20.5 4. O Developmentally-regulated GTP Q9Y295 binding protein 1 40827.3 7 20.4 10 O Suppressor of G2 allele of SKP1 CY2ZO honolog 39699.5 6 20.4 4. O Signal recognition particle subunit C9H89 SRP68 61 33 2 20.4 O 530 13 Regulator of microtubule dynamics O963B5 protein 36O36.2 6 20.4 3. 1805 H/ACA ribonucleoprotein complex Q9NPE3 subunit 3 7763.O 2 20.3 2 34.698 28S ribosomal protein S27, CR92552 nitochondria 4953.6 8 20.3 O 3455 P80723 Brain acid soluble protein 1 2078.7 5 2O2 2 O Translational activator of cytochrome c G93S-4 oxidase 32933.4 4 20.2 9 O P55010 Eukaryotic translation initiation factor 5 49679.O 9 2O2 8 O Patent Application Publication Jul. 6, 2017. Sheet 72 of 141 US 2017/O192012 A1

F.G. 17 (cont'd) PA3246 DNA mismatch repair protein Msh2 O894.1 14 20.2 1O 364.08 O60884. DnaJ honolog subfamily A member 2 463,730 6 202 9 O 39S ribosomal protein L4, Q9BYD3 mitochondria 322962 5 20.2 10 O P55735 Protein SEC13 homolog 35289.5 5 20. 8 O O43491 Band 4.1-like protein 2 92758. 8 20.1 O 3166 P35998 26S protease regulatory subunit 7 49033. 7 20. 9 8724 Peptidyl-prolyt cis-trans isomerase COO688 FKBP3 25233.9 5 20. 4 O C9NZ2 NSF cofactor p47 36637. A. 2O. 6 O H/ACA ribonucleoprotein complex O60832 Subunit 4 53094.7 20.8 O O P3483 Nucleolysin TA-1 isoform p40 42899.0 8 20.0 O O 39S ribosomal protein 2, Q5653 mitochondria 3.3586.8 3 2O.O. 5 O 39S ribosomal protein L14, OSP8 mitochondria 1675.8 A 200 2 O Transmembrane protein 70, C93UB7 mitochondria 29:40.5 S 2O.O. t O O9BUR5 Apollipoprotein O 2.356.2 5 20.O. 1C O Q8WUMO Nuclear pore complex protein Nup133 13OOO57 16 200 9 O p 7812 CTP synthase 1 673748 9 2O.O. 6 O Evolutionarily conserved signating intermediate in Toli pathway, O9BO95 Ocordia 494904 5 20.0 O Very-long-chain (3R)-3-hydroxyacyl Q9PO35 acyl-carrier protein dehydratase 3 4.33877 7 9.9 1O 1 1093 Activator of 90 kDa heat shock protein O95433 ATPase homolog 1 38445.5 5 9.8 6 O CR 16850 Lanosterol 4-alpha demethylase 5929.8 7 9,8 O O HLA class histoCompatibility antigen, PS188 A-30 alpha chain a 90.0 5 19.7 7 O Sodiurnipotassium-transporting PSO993 APase subunit alpha-2 3577.3 17 | 19.7 O O O7595 PRA family protein 3 2648 3 19.7 6 O Pentatricopeptide repeat domain Q96EY7 containing protein 3, nitochondria 75310.4 1 | 19.6 O 124 Putative 60S ribosomal protein 3a Q6NW like NGC87657 1297 3 9.6 10 20138 P2786 Microtubule-associated protein 4 12832.7 8 9.6 O 14724 39S ribosomal protein 10, Q777-8 mitochondria 30051.7 4. 9.5 6 O 05783 Keratin, type cytoskeleta 18 48057.9 7 9.5 3 O Celi growth-regulating nucleolar O9NX58 protein AAO 11 6 9.5 3 O 26S proteasome non-ATPase OOO232 regulatory subunit 2 523.07.0 9 19.5 O O Dolichy-diphosphooligosaccharide-- protein glycosyltransferase subunit P6803 OAD 12667.8 2 9.5 2 5450 C15424 Scaffold attachment factor B1 99339, 14 95 O 173648 Probabie ATP-dependent RNA P2696 helicase DOX6 54816. 8 19.5 1C 8096 O8N36 WD repeat-containing protein 36 106348.8 2O 9.5 O 16164 Q14676 Mediator of DNA damage checkpoint 197572.4 22 9.5 10 A962 Patent Application Publication Jul. 6, 2017. Sheet 73 of 141 US 2017/0192012 A1

FIG. 7 (cont'd) protein U3 Srial nucleolar RNA-associated C9YH9 protein 6 homolog 70823 13 19.4 A. O O994.17 C-Myc-binding protein 9667 4. 19.4 3. O Q9NTK5 Obg-like ATPase 1 39235.5 6 9.4 1O O P25786 Proteasome subunit alpha type- 30,182.7 9 9.4 8 O Aminoacyl tRNA synthase complex O1355 interacting multifunctional protein 2 3569 O. 4 19.4 5 O PS7936 roponyosin alpha-4 chain 3O849 5 9.4 1) O Signal recognition particle subunit O6094 SRP72 7813.2 9 19.3 10 7088 O0844. RNA-binding protein EWS 63783.4 9 9.3 10 1201.97 HLA class histoCornpatibility antigen, CR29960 Cw-6 alpha chain 3926O.O 4. 19.3 10 O Glycerol-3-phosphate dehydrogenase, P43304 nitochondria F5992.0 12 19.3 O O CDGSH iron-sulfur domain-containing CR8N5K. protein 2 15506.3 4. 19.3 8 78993 PO4264 Keratin, type 9 cytoskeleta 1 66209.9 3. 19.3 O 64740 O58P8 RNA-binding protein 26 8623.2 11 19.2 1O 19593 P56 Host ce: factor 91849.1 18 9.2 1C 2588 KRR sma: subunit processome Q36O1 component homolog 404546 8 19.2 1O O SWISNF-reated natix-associated actin-dependent regulator of chromatin O2824. subfamily B member 1 43934.9 5 9.2 2 O OgEY77 Polymerase deta-interacting protein 3 A42O. y 19.1 O O 39S ribosoma protein 3, Q98YD nitochondria 2O749.O 5 19.1 O POTE ankyrin domain family member Q6S83 E 22960.5 16 19.1 10 2345653 O457 Ubiquitin-associated protein 2-like 113076 1 | 19.1 O 17703 P3552 Cystathionine beta-synthase S8521 8 19.1 8 O O994.96 E3 ubiquitin-protein ligase RING2 3811 7 7 19.1 8 O Guanine nucleotide-binding protein PS3O96 G(i) subunit alpha-1 3952O.S 9 8.9 8 26943 Peptidyl-tRNA hydrolase C31, Q41.97 mitochondria 23858.2 5 8.9 7 O Mitochondrial import receptor subunit O96849 TOM8 homolog 8002.0 18.9 A. O Retinoid-inducible serine C9HB40 carboxypeptidase 4222.0 5 18.9 4. O OO6285 Exosome complex component RRP45 45.532.3 8 18.9 1O 26703 PO7099 Epoxide hydrolase 1 53177. 8 18.9 6 O P284.82 Mitogen-activated protein kinase 1 41789.O. 7 18.9 2 O P84O98 60S ribosomal protein 19 2358, 4. 18.9 10 286488 {socitrate dehydrogenase (NAD O43837 subunit beta, mitochondria: AOOO7. 5 18.9 O 25266 tRNA (cytosine(34)-C(5))- CO8J23 methyltransferase 8520.9 1 18.9 10 O OOO267 Transcription elongation factor SPS 121148.7 15 18.8 1O O Acyl-CoA dehydrogenase family Q9845 member 9, mitochondria: 6938.7 12 8.8 3 O P2281 V-type proton ATPase subunit B, brain 56843,O 7 18.8 1 O Patent Application Publication Jul. 6, 2017. Sheet 74 of 141 US 2017/0192012 A1

FIG. 7 (cont'd) isoform PO797 Neurofilament medium polypeptide 80998.5 14 8.8 O 3589.9 OOO341 Vigiin 40499.1 7 18.8 10 2O337 Ras-related C3 boturun toxin P63000 Substrate 22858.0 3 18.8 10 A04O7 P14649 Myosin Fight chain 68 22878. 5 18.8 O O P42766 60S ribosomal protein L35 145515 2 18.7 10 280685 O7568 Acy-protein thioesterase 244. 3. 8.7 4. O Thyroid hormone receptor-associated Ch9Y2W protein 3 108,722.9 6 18.6 O 64249 HLA class histocompatibility antigen, PO4439 A-3 alpha chain 4, 25.9 4. 18.6 s O HLA class histoCompatibility antigen, 3746 A-11 alpha chain A485.8 A. 18.6 1O O HA class histocompatibility antigen, P30a:43 A-1 alpha chain 41310 4. 18.6 5 O HA class histocompatibility antigen,

P3O4585 A-36 apa chai 4129. 4. 18.6 5 O O8D ATP-dependent RNA helicase DDX54 9895.8 15 18.6 10 2237 Putative heat shock protein HSP 90 O58FF6 beta 4 588918 10 18.6 1C 232.98 Pa995 GMP synthase glutamine-hydrolyzing 77456.9 9 18.6 8 O Q03701 CCAATlenhancer-binding protein zeta 1218O14 8 18.6 7 O P53618 Coatomer subunit beta 108283.0 15 8.6 10 3348 Double-strand break repair protein P49959 MREA 794-600 2 8.5 O 1917.3 Eukaryotic transiation initiation factor 3 OOO303 subunit. F 37678.O 8 18.5 10 O V-type proton APase catalytic P38806 subunit A 8870.3.4. 11 | 18.5 2 O P23381 Tryptophan-tRNA ligase, cytoplasmic 584.8 S 8.5 4. O Growth arrest and DNA damage O8 AE8 inducible proteins-interacting protein 1 2540.9 3 18.5 2 O Peptidyl-prolyi cis-trans isomerase O438 FKBP8 45618 6 18.5 10 58O11 6-phosphogluconate dehydrogenase, P52289 decarboxylating 53653.3 9 18.4 8 O 3 sma: nucleolar RNA-associated C9E3W6 protein 14 homolog A 7945.8 3 18.4 O 16572 O5286 Ras-related protein Rab-35 20269.8 3 18.4 1. 98.309 O8mF-5 Nucleoporin NUP53 34.887.9 5 18.4 2 O O0567 AP-1 complex subunit beta-1 04279.9 8 8.4 1. 34953 CR 4696 LDLR chaperone MESD 262478 3 184 4. O HLA class histocompatibility antigen, P3052 A-29 alpha chair A 48.0 4. 184 7 O P8310 AP-2 complex subunit beta 1060348 16 8.4 1O O O9BSC4 Nucleolar protein 0 7785.18 11 18.3 1C O Transmembrane emp24 domain Q9y3A6 containing protein 5 269, 4 18.3 7 O O8N4W Membrane magnesium transporter 8426. 2 183 6 O O5381 Nuclear valosin-containing protein-like 84496. 2 18.3 10 O ATPase family AAA domain-containing Q8NBU5 protein 38959.5 6 183 8 O Q08257 Quinone oxidoreductase 27956.2 3 18.2 2 O Patent Application Publication Jul. 6, 2017. Sheet 75 of 141 US 2017/0192012 A1

F.G. 17 (cont'd) C98T78 COP9 signalosome complex subunit 4 A3518. 8 18.2 4. O Ribosomal RNA processing protein P5682 honolog A 53067.4 8 18.2 7 63720 O 4739 anin-B receptor 71102.5 9 18.2 10 132O48 Q8TCT9 Minor histocompatibiity antigen H3 A 1374 5 8.2 53433 COO 170 AH receptor-interacting protein 38092.3 4 18.2 O POO.3a Dihydrofolate reductase 21509,8 5 182 O Nuclear inhibitor of protein C:2972 phosphatase 1 31404.8 7 182 O O insulin-like growth factor 2 mRNA C9Y6M binding protein 2 6031. 10 18.2 O 3840 Tyrosine-protein phosphatase non P18031 receptor type 1 50537.2 11 18.2 9 26748 C8NF4 Putative protein FAM10A5 41605.9 7 18.2 10 O O959.83 Methyl-CpG-binding domain protein 3 31128.8 4. 18.2 4. O G2996 Ceavage stimulation factor subunit 3 83.377.9 12 8.1 224O7 t-aminoadipate-semialdehyde dehydrogenase-phosphopaintetheinyl Q9NRNA transferase 36OO41 7 18. O 8NF-4 Nucleoporin Nup37 37:63.9 5 18.1 2 O C9NW84 Pre-?nRNA-spicing factor RBM22 45589.3 6 18. 6 O Mitochondrial antiviral-signating C7ZA34 protein 48.897.3 5 18. 4. O Eukaryotic translation initiation factor 4 QG4637 gamma 1 166255.4 20 18.0 10 299.745 O4910 Protein in-7 homolog A 26,8 A. 8.0 O O4204 Cytoplasmic dynein heavy chain 53546.0 71 18.0 1.O. 32O67 Transcriptional activator protein Pur COO577 alpha 35O24.9 3 18.0 1 O Puronycin-sensitive aminopeptidase A6NEC2 like protein 54260.6 7 18.0 4. O O94973 AP-2 complex subunit alpha-2 96.748.8 13 18. 10 O P28072 Proteasone subunit beta type-6 25585.9 8 18.0 6 O CSNX47 E3 ubiquitin-protein ligase MARCH5 318O2. 8 18.0 3 O C3505 Metaxin- 43855.2 7 18. 4. O O94776 Metastasis-associated protein MA2 757646 12 18.0 10 O C9-44 Sentrin-specific protease 3 65637.2 8 17.g 3 O Eukaryotic translation initiation factor 3 C 5372 subunit 4C1015 7 7.g 2 O O6093 Sorting nexin-3 6988.4 A. 17.9 7 O Cin-associated NEDO8-dissociated CR86WP6 protein 126241.7 20 17.9 O 15981 CD2 antigen cytoplasmic tail-binding O9500 protein 2 37760.6 6 17.9 4. O Eukaryotic translation initiation factor 3 O9885 So K 2.5344.9 A. 17.9 4. O 8W2 Nucleolar complex protein 3 homolog 930041 13 7.9 10 54,058 Eukaryotic translation initiation factor 3 O 4152 Sbunit A 186968.8 24 7.9 10 79584 P3508) Profin-2 54095 3 17.9 2 O Zinc finger CCCH domain-containing O8WU90 protein 15 A900 8 17.8 8 O PA613 Antigen Ki-67 34.805. 4 7.8 10 5.783 Patent Application Publication Jul. 6, 2017. Sheet 76 of 141 US 2017/0192012 A1

F.G. 7 (cont'd) C9BR6 Serinefarginine-rich splicing factor 8 31970. 5 17.8 O O081G Serinelarginine-rich splicing factor 4 56792.5 9 7.8 O 123236 P6009 Signal peptidase complex subunit 3 2O370.5 4 17.8 8 O O9-08 Septin-9 6235.7 8 178 5 O O95757 Heat shock 70 kDa protein 4 955392 3 78 10 O 3-hydroxyisobutyryl-CoA hydrolase, Q6NVY1 mitochondria: 4089.5 6 17.8 10 O Polyribonucleotide C8CS8 nucleotidyltransferase 1, mitochondrial 86578.1 13 178 O O 26S proteasome non-ATPase O00487 regulatory subunit 14 3474-82 4 7.7 9 35802 OA690 Protein RRP5 homolog 21 OO69.7 30 17.7 O 21803 CR96AX2 Ras-related protein Rab-37 24OFO.8 2 17.7 10 O Mitochondria import inner membrane OA925 transiocase Suibunit in23 224.3 2 17.7 4. 45531 CR 13330 Metastasis-associated protein MA 714.O.3 12 17.7 10 20442 O9525 Histone acetyltransferase KA7 60910.6 8 17.7 10 O O4379 HIV Tat-specific factor 8.6423.2 12 7.6 8 3O878 Q9NORC3 Reticulon-4 81797.5 9 7.6 O 1OC56 O95232 luct-like protein 3 5865.4 7 176 7 O C49A26 Putative oxidoreductase GLYR 5744.3 8 17.6 10 O Enhancer of mRNA-decapping protein O6P2E9 A. 31778.2 13 76 10 O Coiled-coil domain-containing protein Q96ER9 5 39933.9 6 7.6 4. O C9.884 Ataxin-10 50486.5 8 17.5 4. O P3324O Cleavage stimulation factor subunit 2 60219.8 10 7.5 O 23874 Q847 40S ribosomal protein S4, Y isoform 2 298.37.8 6 17.5 10 8 Endoplasmic reticulum resident O9BS28 protein 44 A737O.S 6 17.6 4. O O75694 Nuclear pore complex protein Nup155 537984 15 175 10 3903 Nucleolar and coiled-body O 14978 phosphoprotein 74-0318 1 17.4 10 100.79 Vacuolar protein sorting-associated O75436 protein 26A 35206.8 5 7.4 6 O P55786 Puromycin-sensitive aminopeptidase O3960.8 15 174 9 6347 Q9Y696 Chloride intracellular channel protein 4 298.00.3 2 7.4 1 O Glycine cleavage system H protein, P23434 ritochondria: 1912.7 3 17.3 A. 6O156 P98.175 RNA-binding protein 30 99293.8 11 17.3 10 O C98XK5 Bcl-2-like protein 13 528373 5 73 O O9WXO Ubiquilin-1 6O966.7 7 7.3 O 32766 C9688 E3 ubiquitin-protein Eigase UHRF 92005.0 15 17.3 O O U3 snai nucleolar RNA-associated C9Y51 protein 18 homolog 62459.9 1 | 73 8 2O565 HLA class histoCompatibility antigen, PO891 A-68 alpha chain 41940 4. 17.3 7 O hLA class histoCompatibility antigen, PO321 Cw-7 alpha chain 41618 A. 17.2 9. 5502.5 HLA class histoCompatibility antigen, O29963 Cw-6 alpha chain 41425. 4 17.2 5 3247 HLA class histocompatibility antigen, P30508 CW-12 alpha chain 41342.8 4 17.2 7 O Patent Application Publication Jul. 6, 2017. Sheet 77 of 141 US 2017/0192012 A1

FIG. 7 (cont'd) O983 Methyltransferase-like protein 7A 23832.4 3 17.2 1 O P16402 Histore -3 22349.9 7 17.2 10 O 39S ribosomal protein L39, O9NYK5 mitochondria 40089.7 6 17.2 8 O Ubiquitin carboxyl-terminal hydrolase Q93009 7 129385.9 18 17.2 1O 5360 Ras GTPase-activating protein-binding O9 N86 protein 2 52526.4 6 17.2 2 O P631 73 60S ribosomal protein 38 8274.9 1 17.1 9 57987 O9BW38 WD repeat-containing protein 18 48O89.6 8 17. 5 2609 28 kDa heat- and acid-stable O3442 phosphoprotein 20630.O 3 7. 2 O Double-strand-break repair protein O60218 fad21 homolog 7 1974.8 9 7. 8 O O99815 DnaJ honofog subfamily C member 7 54.394.5 O 17. 9 O O98Y67 Cell adhesion molecule 1 4339.9 4. 17.1 4. O O6NXT2 Histone H3.3C 5327.8 4 17.0 10 O Serie? threonine-protein phosphatase P53041 5 57449.0 8 17.0 2 O OOO15 PDZ and Liv domain protein 1 36528.0 5 17.0 2 O O9282O Gamma-glutanyl hydrolase 36.363.6 5 17.0 O P62861 40S ribosonal protein S30 6647.9 17. 143220 Transmembrane emp24 domain O5363 containing protein 2 22875.3 6 169 4. 96240 Mitochondrial intermembrane space O8N4O import and assembly protein 40 170613 1 16.9 2 O O 523 WD repeat-containing protein 46 685274 9 16.9 7 O

O9 KK9 ADP-sugar pyrophosphatase 2462.8 3. 69 2 O CR 5155 Noda nodulator 1352936 7 | 16.9 10 74O2 P69849 Noda nodulator 3 135103.2 6 16.9 10 O O5PE7 Nodai nodulator 2 37.842 8 16.9 O O Q9MX5 Neudiesin 88564 3 16.9 1 O U3 smal nucleolar ribonucleoprotein O9NW31 rote MP3 2964.2 4. 16.9 6 O P484.44 CoatOmer Subufit delta 53.523.2 6.8 10 38277 O53E 6 Programmed cel death protein 4 51554.9 8 6.8 10 O SWISNF-related matrix-associated actin-dependent regulator of chromatin O969G3 subfamily E member 44328.8 6 16.8 4. O PO2768 Serum albumi 626.35.6 O | 16.8 10 60542 39S ribosomal protein 19, P494.08 mitochodria 33820.2 6 168 6 O P20339 Ras-related protein Rab-5A 23886.8 5 16.7 9 O Q9UGP8 Translocation protein SEC63 homolog 88396.3 13 | 16.7 8 O 4/U6 snail nuclear ribonucleoprotein O43395 Prp3 777.00.2 8 16.7 4. O O9B9 Nuclear RNA export factor 8.2126.8 10 16.8 7 O 28S ribosomal protein S30, Q9NP92 mitochondria 5O992.1 5 16.6 3 O P37837 Transaidolase 377 13 6 16.6 7 46815 O8W 68 Splicing factor U2AF 26 kDa subunit 2.3848.7 3. 16.6 1. O Heterogeneous nuclear O8WWV9 ribonucleoprotein -like 6O723.9 8 16.6 1O O Patent Application Publication Jul. 6, 2017. Sheet 78 of 141 US 2017/0192012 A1

FIG. 7 (cont'd) Endothetia differentiation-related O60869 factor 15953. 3 16.6 4. O P5705 Synaptoanin-2-binding protein 15928.1 2 66 2 O O9875 Protein CMSS1 321695 4. 16.5 1 O Q9BWF3 RNA-binding protein 4 32923.O 7 18.5 1.O. 58629 Q9NRG9. Aladin 58839. | 16.5 O O HLA class histocompatibility antigen, PO553 A-24 alpha chain 4O973.8 4. 16.4 5 O HLA class histocompatibility antigen, P3O447 A-23 alpha chain 4 O178 4. 18.4 5 O transcription elongation factor A P2393 protein 3.3657.3 5 16.4 3. O P5270 DNA mismatch repair protein Mshö 138157.0 8 16.4 1O 2094. O9NRW1 Ras-related protein Rab-68 23575.8 3 184 9 O OO541 Pescadio homolog 6883.3 9 16.3 O O P182O6 Wircuir, 1627.6 19 18.3 O 2513 MOSC domain-containing protein 1, Q5VT66 mitochondria 390 18.4 5 16.3 4. O HLA class histocompatibility antigen, P18463 B-37 alpha chain 40742 4. 18.3 5 O HA class histocompatibility antigen, P3O480 B-8 alpha chain 40873.1 4. 18.3 5 O HLA class histocompatibility antiger, P3O462 B-34 alpha chain 48700.2 A. 16.3 5 O HLA class histoCompatibility antigen, P30480 B-42 alpha chain 4O675. 4 16.3 5 O HA class histocompatibility antigen, P3O492 B-54 alpha chain 4O665.2 4. 183 7 O HA class histocompatibility antigen, P3O493 B-55 alpha chain AO7813 4. 16.3 7 O HLA class histocompatibility antiger, O29940 B-59 alpha chain 48869.6 4. 16.3 7 O4444 Caprin- 77785.1 11 | 16.3 O 534:37 Eukaryotic translation initiation factor 3 O582 Subunit 29 76.5 7 16.3 2 O P61758 Prefodin subunit 3 22829.1 5 16.2 3 O O0504.8 Cleavage stimulation factor subunit 4.9156. 7 18.2 3 O Signal peptidase complex catalytic P67812 subunit SECA 20.825.4 5 16.2 8 12621 P28639 threonine-tRNA ligase, cytoplasmic 86O892 1C 182 O O HA class histocompatibility antigeri, P1034 A-32 alpha chain 41.3333 4. 16.2 7 O HLA class histocompatibility antiger, 1689 A-31 alpha chain a 3289.1 4. 16.2 7 O HLA class histoCompatibility antigen. 16190 A-33 alpha chain 4; 177.0 4. 16.2 7 O HLA class histocompatibility antigen, P30453 A-34 alpha chain A340, 4. 182 7 O HA class histocompatibility antiger, P3O459 A-74 alpha chain 41176.O. 4. 16.2 7 O NAD(P) transhydrogenase, C 3423 nitochondfia 14637.2 13 16. 10 251.18 DNA-directed RNA polymerases and O1518O Sbnit RPAC1 392O4.9 4. 18. 8 O P2283O Ferrochelatase, mitochondria 488 A.O. 6 16.1 2 O Patent Application Publication Jul. 6, 2017. Sheet 79 of 141 US 2017/0192012 A1

FIG. : 7 (cont'd) Acidic leucine-rich nuclear Q98O phosphoprotein 32 family member E 3092O6 5 6.0 3 O Cytochrome c oxidase assembly Q7KZN9 protein COX15 homolog 45275. 4. 6.0 10 O C5H9 RRP12-ike protein 39248.8 17 | 8.0 10 28996 O75955 Fotii-1 47583.5 7 | 15.9 5 O Cold shock domain-containing protein O75534 E. 894O7. 14 | 15.9 O O Cyclic AMP-responsive element P1622O binding protein 32632. 3. 15.9 6 O P18583 Protein SON 246419 8 || 5.9 10 17007 Methylmalonyl-CoA mutase, P22033 mitochondria 83590.9 3 || 5.9 4. 14853 P61964 WD repeat-containing protein 5 3 1588 5 5.9 3. O Q9NZ, 7 Mitochondria carrier honolog A 74.2 6 15.9 4. O O3363 C-terminal-binding protein 474.264 5 15.9 O O Q96(R Zinc finger RNA-binding protein 1181.52.8 6 | 15.8 A. O Polypeptide N Q104.71 acetylgalactosaminyltransferase 2 65474.2 O | 15.8 7 O P46459 Vesicle-fusing ATPase 83107.8 3 || 5.7 10 284.64 Double-stranded RNA-binding protein O95793 Staufen homolog 58164.3 9 5.7 6 O CR9-36 Polyadenylate-binding protein 3 70259.2 O | 15.7 O O Zinc finger CCCH domain-containing O7552 protein 1A 89986.6 13 || 5.7 3 O P5774. O Nuclear pore complex protein Nup107 O7 5.6 4 || 5.7 8 O C9H583 HEAT repeat-containing protein 1 244537.7 33 5.7 10 22,725 Eukaryotic peptide chain release P1570 factor GTP-binding subunit ERF3A 6289.2 7 5.6 6 O OOO767 Acyl-CoA desaturase A 8938 4. 15.6 6 S4731 P53675 Clathrin heavy chan 2 85.716.4 26 5.6 C Zinc finger CCCH domain-containing Q6PJ7 protein 4 772740 9 15.6 7665 pre-mRNA 3’ end processing protein O9C08 WDR33 O7737. 6 15.6 3. { Q9HCS7 Pre-mRNA-splicing factor SYF1 100808.2 1 || 15.8 2 O O95716 Ras-related protein Rab-3D 24495.3 4. 5.5 10 O P36871 Phosphogluconutase- 62933.6 10 || 5.5 2 O Williams-Beuren syndrome CR9651 chromosomal region 6 protein 50738.2 6 || 5.5 4. O p11171 Proier 4. 8228. O || 5.5 O O Q8N8A6 ATP-dependent RNA helicase DDX5 73027.7 8 || 5.5 6 O P49790 Nuclear pore complex protein Nup153 55.535.3 17 | 5.5 10 380 P4227 N-alpha-acetyltransferase O 25792.2 2 15.5 2 O P17480 Nucleolar transcription factor 1 8753.7 3 || 5.4 10 555.99 Calcium homeostasis endoplasmic Q8WX8 reticulum protein O425.8 1 || 5.4 9 O P17858 6-phosphofructokinase, liver type 885234 1O 5.4 6 O F-actin-capping protein subunit alpha P47755 2 33177.2 4 S4 5 O CR969ZO Protein BRG4 66230.5 9 || 5.4 O 34.82 U3 small nucleolar RNA-interacting O4388 protein 2 524,680 7 | 15.4 4. Patent Application Publication Jul. 6, 2017. Sheet 80 of 141 US 2017/0192012 A1

F.G. 17 (cont'd) Growth hormore-inducible Q9-3K2 transmembrane protein 37364 6 15.4 7 O Receptor expression-enhancing COO765 protein 5 27213 3 15.3 2 O Q58FF3 Putative endoplasmin-like protein A632.3 7 15.3 9 O CR 12769 Nuclear pore complex protein Nup160 49024.0 16 15.3 O 2222 O4344. Peptidyl-prolyl cis-trans isomerase H 94.93.3 4 15.3 4 O Signal recognition particle receptor P08240 subunit alpha 8864.2 8 15.3 2 O O90C2 ADPfAP translocase 4 353.07. 6 15.2 O O O5226 NF-kappa-B-repressing factor 78.357.3 10 5.2 3 1626.5 P6435 NADPH-cytochrome P450 reductase 7746. 11 15.2 7 28554 Growth factor receptor-bound protein P62993 2 25320.4 6 15.2 2 O PS2565 Rho GOP-dissociatio inhibitor 23264.2 3 15.2 8 595 Q86X2 Acyl-coenzyme A thioesterase 1 A6676.8 5 15.2 3 O O9 G3 Tyrosine-protein kinase BAZ1B 172272. 9 15.2 1O 30.522 P371.98 Nuclear pore glycoprotein pó2 53426. 6 15.1 9 O 26S proteasome non-ATPase P51665 regulatory subunit 7 37082.5 5 151 6 O P7661 Desmin 53592.9 O 15. O O C9Y697 Cysteine desulfurase, mitochondrial 46552.9 9 15.1 6 O Q9MQW7 Xaa-Pro aminopeptidase 1 7.332.1 8 15.1 6 O Anaphase-promoting Complex subunit C933X3 7 8598.8 8 15.1 3 O Q96BM9 ADP-ribosylation factor-ike protein 8A 26441 4. 15.1 2 50259 ATP-binding cassette sub-family E P6 22 member 1 88283.9 9 15.0 10 O COP-diacylglycerol-inositol 3 O 14735 phosphatidyltransferase 2388C 3 15.O 6 O Eukaryotic translation initiation factor 3 C9963 subunit C 6028.3 15.O 1O 33 12.5 Q9NYF8 Bcl-2-associated transcription factor 99.673.9 14. 15.O. O 136926 Serine/threonine-protein phosphatase P6050 4 catalytic subunit 35650.2 6 150 4 O Succinate-semialdehyde P5649 dehydrogenase, mitochondrial 58789.8 6 150 8 O O962 60S ribosomal protein 10-like 24975. 3. 150 6 O P56.192 Methionine-tRNA tigase, cytoplasmic 102313.5 14.9 O 3023 ALOO Acetolactate synthase-like protein 884.95. 6 A.9 4 O C967 Protein disfide-isonease MX3 37.366.8 4. 14.9 2 O O75787 Renin receptor 390O8. 4 14.9 O P47897 Glutamine-tRNA ligase 88713 3 148 6 O Peptidyl-proly cis-trans isomerase-like Q8WUA2 || 4 57738.4 9 148 2 O DNA fragmentation factor subunit OOO273 alpha 36921.1 5 148 2 O O15258 Protein RER 23072. 2 148 2 O O95782 AP-2 complex subunit alpha-1 175373 13 148 1O O Q96FW1 biquitin thioesterase CTUB 33598.3 4 14.8 2 O Probable ATP-dependent RNA O9BUCR8 helicase DDX23 959248 4 148 9 O C93ZF Oxystero-binding protein-related 99.95.9 O 14.8 3. O Patent Application Publication Jul. 6, 2017. Sheet 81 of 141 US 2017/0192012 A1

FIG. 17 (cont'd) protein 8 P13645 Keratin, type I cytoskeletal O 59055.3 11 14.7 5 SOO9 Exonuclease 3'-5' domain-containing Q9NWHO protein 2 62826.7 8 14.7 5 O PA 129 Peripherin 53829. 7 14.7 O O O9BRKS 45 kDa calcium-binding protein 32619.4 6 14. O O 39S ribosomal protein 37, O982E1 mitochondria 48.630.8 7 14. 4. O HA class histocompatibility antigeri, PO1889 8-7 alpha chain 408O2.3 5 4.6 3 O C. 487 Kinesin-like protein KF22 73661.5 10 146 3. i5777 Spermatid perinuclear RNA-binding O96S9. protein 73494.1 14 14.6 O 378 CR96KP4 Cytosolic non-specific dipeptidase 4.8669.6 6 14.6 2 O CSN.W3 RNA-binding protein 28 78229.5 O 14.6 10 O Na(+)/H(+) exchange regulatory O A45 cofactor N-ERF 39153.6 7 14.5 2 29488 Mitochondrial genome maintenance C98CRP7 exonuclease 3982O2 4. 4.5 O H: A class histocompatibiity antigen, P3.504 Cw-4 alpha chain 41394.2 4. A5 7 O Hi A class histocompatibiity antigen, P3050 CW-14 alpha chain 41293.9 4. 14.5 7 O Signal recognition particle 54 kDa P6101 protein 53293.9 9 45 4. O HLA class histoCompatibiity antigen, 29865 Cw-18 alpha chain 41389.2 4. 14.5 5 O P4794. 60S ribosomal protein 29 178091 2 14.5 O 2296 Q9NY61 Protein AAF 63247.1 7 4.5 9 16350 C9Y247 Protein FAM50B 38765.8 5 14.5 7 O Wacuolar protein sorting-associated C96CK1 protein 35 92505,6 2 14.5 9 2276 CR5428 Splicing factor 3A subunit 2 4.9369.7 7 44 7 O C. 424.7 Src substrate contactin 82683.9 7 44 8 O P58546 Myotrophin 13065.9 2 14.4 O Cob()yrinic acid a,c-diaride C96EY8 adenosyltransferase, mitochondria 27730.5 3 14.4 3 19104 Putative mitochondrial import inner membrane transiocase stoun C5SRD1 23B 28333.6 3. 144 4. O CR9PO03 Protein corrichon homolog 4 16435.6 2 14.4 7 52434 39S ribosomal protein 3, PO9001 rtochondria 38.917.8 5 144 1 O P29372 DNA-3-methyladenine glycosylase 32923.9 4. 14.3 8 O (8NH-9 Atlastin-2 6658.5 5 14.3 4. O C9-W9 Prefoldin subunit 2 16049 2 14.3 1 O Putative tubulin beta chain-like protein A6NKZ8 ENSPOOOOO290377 4223.4 14.3 10 O C4254 Fotii-2 47463,4 7 143 3 O P3524.1 Radixir 63113.4 9 142 10 O Q5 V8 orsin-A-interacting protein 6649.6 8 4.2 2 O CSTZ9 Alanine-tRNA tigase, mitochondrial 108.367. 13 142 4. O PA209 CD99 antigen 18045.0 2 14.2 2 O Patent Application Publication Jul. 6, 2017. Sheet 82 of 141 US 2017/0192012 A1

FIG. 7 (cont'd) Cell division cycie and apoptosis O8X2 regulator protein 3266.6 13 || 4.2 10 34.3665 39S ribosoma protein .27, C9 OV19 rtochondria 16129.9 2 14.2 2 O Probabie ATP-dependent RNA GR9Y2R4. helicase OOX52 6784.O.3 6 14.2 O O Q1415 Scaffold attachment factor 82 107986.8 13 || 4-2 10 126735 Nucleaf protein localization protein 4 O8A8 homolog 696746 8 4. 6 O Vitamin Kepoxide reductase Complex C9E3CBS subunit 153.35.7 1 4.1 9 41205 RAF3-interacting JNK-activating Q9Y228 nodulator 63.23.4 8 14.1 2 O Q0288 Niceobindi- 53.8794 8 4. 1 C9C9 NADH-cytochrome b5 reductase 1 34266. 6 || 14.1 2 O Putative HEA class histocompatibility PO893 antigen, alpha chain H A1120. 3 14. 3. O Cation-dependent mannose-6- P20645 phosphate receptor 31506.8 2 11 1 O GR9Y3C Nucleolar protein 16 244.75.6 3 AO 4. O CRO 1813 6-phosphofructokinase type C 86508.7 8 || 4.0 2 O Methylmalonate-semiaidehyde dehydrogenase acylating, CO2252 mitochondria 58236. 6 14.0 2 O O60RAS Putative histone H2B type 2-D 1847.3 4 || 4.0 | 10 O O9Y490 air- 27 1934.6 30 | 40 10 7365 O00505 importin subunit alpha-4 58.324.2 5 14. 7 O Guanine nucleotide-binding protein P63092 G(s) subunit alpha isoforns short 4559.8 8 14.O 10 O9AB7 tubulin beta-1 chain 58973 S 14.O 10 CR6P 39 Parafibromin 60690.7 7 13.9 2 O Eukaryotic translation initiation factor O6084 58 39283.3 14 || 13.9 10 24282 General vesicular transport factor O60783 p115 O9457.5 14 || 13.9 O O Succinyl-CoA iigase ADPFGDP P53597 forming subunit alpha, mitochondrial 36649. 4 13.9 2 O Q96RP9 Elongation factor G, mitochondria 85.245.9 13 13.9 O 1157 Q9Y276 Mitochondrial chaperone BCS A7705.4 7 13.8 1 O P15259 Phosphoglycerate mutase 2 28937.3 3 3.8 O O 2-oxoglutarate dehydrogenase, CO2.218 ritochondria 1 O778.8 1 13.8 O O ER membrane protein complex C8N 766 subunit 1583 12 38 10 2543 CR86XP3 ATP-dependent RNA helicase DDX42 96.807.0 14 13.8 10 2O706 Mitochondrial import receptor subunit C15388 foM20 homolog 16469.0 2 3.8 3 O O75530 Polycomb protein EED 5O297.8 6 3.8 9 O P48651 Phosphatidylserine synthase 1 5622.0 6 13.7 4. O HA class histocompatibility antigen, O95604 Cw-17 alpha chain 41837.5 3. 13.7 7 O ATP synthase subunit delta, P300.49 mitochondria 17490.0 3 13.7 O 163527 long-chain fatty acid transport protein O6P MO 4 72976.8 1O 3.7 3 O Patent Application Publication Jul. 6, 2017. Sheet 83 of 141 US 2017/0192012 A1

FEG, 7 (cont'd) O7584.4 CAAX preny protease 1 honolog 55098. 5 13.7 6 O O968 RHO complex subunit 3 39456. 3 3.7 1 28S ribosomal protein S26, C9E3YN8 mitochondria 24288.8 S 3.7 O PO6737 Glycogen phosphorylase, Siver form 955122 15 13.7 8 O PO796 Neurofilament light polypeptide 61573.7 7 13.6 10 O Proline-, glutamic acid- and leucine CR828 rich protein 29487.4 2 13.6 O O Q9Y678 Coatomer subunit gamma-1 99.03O. 32 13.6 2 O Sodiurnipotassium-transporting Q13733 APase subunit alpha-4 1593.2 4 3.6 1C O POSA93 tropomyosin alpha-1 chain 3.1315 A. 3.6 1. C15061 WD repeat-containing protein 43 75862 9 36 8 3.138.5 P28232 Catenin alpha-2 91783.3 5 13.6 10 O Pre-rrNA-processing protein TSR C2NL82 honolog 92.209A O 3.6 2 O P224.92 Histole H. 2209. A. 13.5 10 O P06280 Alpha-galactosidase A 495.08.2 5 3.5 5 O 28S ribosomal protein, S2, Q9Y399 mitochondria 33534.4 8 3.5 6 O C9EXS5 AP- complex subunit mu- 49.3848 1O 3.5 4. O C9UHD9 Ubiquilin-2 65696.3 5 135 2 O Zinc finger CCCH-type antiviral protein CFZ2WA 81259.2 11 3.5 10 O GR9 NH7 Sorting nexin-6 4O3948 4. 13.5 2 O O76003 Glutaredoxin-3 3777.2 5 3.4 3 O O08043 Alpha-actinin-3 O3982.9 12 3.4 O O Glucose-6-phosphate - P 1413 dehydrogenase 82345.0 7 34. 6 O HLA class I histocompatibility antigen, P30505 Cw-8 alpha chain 41229.0 3 3.4 5 HiA class I histocompatibility antigen, Q07000 CW-15 alpha chain 439.1 3 3.4 5 O HA class histocompatibility antigen, Q9INN7 Cw-5 alpha chain 41368.2 3 3.4 4. O Eukaryotic translation initiation factor PO6730 AE 27292.0 4. 13.4 6 2459 O94874 E3 UFM1-protein ligase 1 794.73.4 2 3.4 O O C1A26 Desmogiein-2 2392.5 11 3.3 4. O PO7203 Glutathione peroxidase 22223.3 3 3.3 2 O O9ULW4 Coroni-C 53933.5 7 3.3 1C 56.66 P784 / Glutathione S-transferase omega- 26743.0 4 3.3 5 O RNA-binding motif protein, X-linked O75526 like-2 A-2986.4 7 3.3 O O Q9P289 Serine/threonine-protein kinase MST4 a 566.1 5 3.3 3 O GR98,27 Nuclear pore complex protein Nup85 75875.O. O 33 5 O Q9H7Z7 Prostaglandin E synthase 2 424.3 5 3.3 2 O Acyl-coenzyme A thioesterase 2, PA9753 mitochondria 5367.8 5 3.3 3 O Q9BWV7 Siceroflexin-3 36321 4. 3.2 7 O O(6)-methylguanine-induced CR5-74 apoptosis 2 322.2 3 13.2 3 O P35609 Alpha-actinin-2 04424.3 17 | 3.2 O O Patent Application Publication Jul. 6, 2017. Sheet 84 of 141 US 2017/0192012 A1

FIG. 7 (cont'd) Dolichyl-diphosphooligosaccharide protein glycosyltransferase subunit PA6977 STT3A 81157.1 9 3.2 1O S1939.5 Ch9NOT4 Exosome complex component RRP46 25762.2 4 3.2 ? O Putative heat shock protein HSP 90 O58FG alpha A4 47826.0 5 3.2 9 O HLA class histoCompatibility antigen, P 13747 alpha chain E AO384.9 5 3.1 3. O Q9262 Nuclear pore complex protein Nup205 230317.0 24 3. 10 A 522 P4O938 Replication factor C subunit 3 384.83.3 3 13.1 2 O 39S ribosomal protein 9, O9BYO2 mitochondria 3O444 3 13.1 5 O O4744 Protein arginine N-methystransferase 5 72658.0 9 13.0 t 19506 Basic leucine zipper and W2 domain Q7 CR6 containing protein A7249.8 13. 8 O P14923 Junction plakoglobin 82.486.3 S 13.0 6 O ATP-binding cassette sub-family F O8NE 71 ember 94.2594 1O 13.0 10 O HLA class histoCompatibility antigen, P103.19 B-58 alpha chain 4O622.3 3 13.O 5 O HLA class histocompatibility antigen, P8464 B-51 alpha chain 408515 3. 13.0 5 O HLA class histocompatibility antigen, P18465 B-57 alpha chain AO566.4 3 13.O 5 O HLA class histocompatibility antigen, P3O464 B-15 alpha chain 4O6732 3. 13.0 5 O HLA class histocompatibility antigen, P30475 B-39 alpha chain AOS 70.2 3 13.O 3. O HLA class histocompatibility antigen, P3O484 B-46 alpha chain 4O725.4 3. 13.0 5 O HLA class histocompatibility antigen, P3O490 B-52 alpha chain 40806.4 3 13.O 5 O HLA class histocompatibility antigen, P3O49 B-53 alpha chain 4O78C5 3 13.0 5 O HLA class histocompatibility antigen, P3O495 B-56 alpha chain AO763.4 3 13.0 S O HLA class histocompatibility antigen, P3O498 B-78 alpha chain 4O7633 3 13.0 5 O HLA class histocompatibility antigen, P30685 B-35 alpha chain AO740.4 3 13.O S O HLA class histocompatibility antigen, O297.8 B-82 alpha chain 4O7O63 3 13.0 3 O HLA class histoCompatibility antigen, O29836 B-67 alpha chain AO627.2 3 13.O 3 O HLA class histocompatibility antigen, O95365 B-38 alpha chain 407584 3 13.0 3 O O5427 Splicing factor 38 subunit 4 44442.9 3 130 10 O7868 PBO39C Gutathione reductase, mitochondria 5224.7 6 3.0 1O O U4/U6 small nuclear ribonucleoprotein Q8WWY3 Prp3 46293.5 7 2.9 1O O HLA class histocompatibility antigen, P84.62 A-25 alpha chain 4503.2 3 2.9 3 O HLA class histocompatibility antigen, P30450 A-26 alpha chain A 347. 3 2.9 3 O HLA class histocompatibility antigen, P3O458 A-43 alpha chain 438.0 3 2.9 3 O P3O457 HLA class histocompatibility antigen, 41367. 3 12.9 3 O Patent Application Publication Jul. 6, 2017. Sheet 85 of 141 US 2017/0192012 A1

FIG. 17 (cont'd) A-66 alpha chain Peroxisomal acyl-coenzyme A oxidase O15067 1 73589. 7 2.9 6 O P6962 DDB- and CU4-associated factor 7 39553.5 5 12.9 6 O O96KSO Eg nine homolog 2 4262.9 6 2.8 2 O GTP:AMP phosphotransferase AK3, C9. mitochondria 2 590.5 3 2.8 6 O Protein transport protein Sec61 P6619 subunit alpha isoform 4892. 7 2.8 6 O Small glutamine-rich tetratricopeptide O43765 repeat-containing protein alpha 34291.3 4. 2.8 3 O Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta P3O154 isoform 67558.6 2.8 10 O Pre-mRNA-processing factor 40 O75400 homolog A OP5044 13 2.8 54761 POTE ankyrin domain family member ASA3EO 12398.6 10 | 12.7 10 O O43159 Ribosoma RNA-processing protein 8 5456.2 5 2.7 1 O isowateryl-CoA dehydrogenase, P26440 fritochondria 45035.2 3 2.7 4. O Probable global transcription activator P28370 SNF2L-1 22557.9 17 | 2.7 10 O C6Q22 Ras-related protein Rab-32 27.5908 3 12.7 1. O Ribosome biogenesis protein NSA2 O95478 homolog 302366 3 2.7 2 O PO4792 Heat shock protein beta-1 22839.6 4. 2.7 1 O O98XYO Protein MAK16 homolog 357 10.8 8 12.7 2 O O9NZO1 Very-long-chain enoyl-CoA reductase 36433.6 4. 12.7 5 4991 Structural mainterance of Q9NJ3 chromosomes protein 4 44414.6 6 2.7 O O C6ZMR3 L-lactate dehydrogenase A-like 6A 3.6849.6 5 12.7 10 O O925.26 T-complex protein 1 subunitzeta-2 5764.9 6 26 10 94.683 P61028 Ras-related protein Rab-5B 2626.8 3 2.6 10 O C6EEWS Small ubiquitin-related modifier 4 10742.2 1 26 10 O O13427 Peptidyl-proly cis-trans isomerase G 64943. 5 12.6 1C O Phosphatidylinositide phosphatase CR9N5 SAC 6,480.3 9 2.6 8 O Q9HK6 Alpha-methyacyl-CoA racemase 43465.8 3 2.6 2 O 28S ribosomal protein S5, P82675 mitochondria 4859.8 8 2.6 O Calciumlcaimodulin-dependent protein Q13557 kinase type subunit delta 57 1013 4 2.6 10 O C95373 importin-7 120828.4 13 2.5 7 O lysosome-associated membrane P.11279 glycoprotein 1 45395.7 4. 12.5 3 O Q9UEY8 Ganna-adducin 77755, 7 12.5 6 24. A Guanine nucleotide-binding protein PC947.1 G(o) subunit alpha 40.693.4 5 2.4 6 O HA class histocompatibility antigen, P3046.6 B-8 alpha chain 40580.0 3 2.4 4. O HA class histoCompatibility antigen, P3O479 B-4 alpha chain 4.08814 3 2.4 5 O P49792 E3 SUMO-protein ligase RanSP2 36259.8 38 24 O 17621 Patent Application Publication Jul. 6, 2017. Sheet 86 of 141 US 2017/0192012 A1

FIG. 17 (cont'd) P53985 Monocarboxylate transporter 54.628.6 5 12.4 3 O G patch domain and KOW motifs CR92917 containing protein 52457.O. 5 12.4 1 O Putative tropomyosin alpha-3 chain A6N28 Eke protein 25877.3 4. 12.4 10 O PO8729 Keratin, type 3 cytoskeletal 51442.8 O 12.4 O O CR13428 Treace protein 450.3 A 2.3 10 47540 Programmed ceil death 6-interacting C8WUM4 protein 97.025.0 2 12.3 O O Carnitine O-palmitoyltransferase 2, P2386 itochondria 4290.4 O 12.3 3 O PC5556 integrin beta-1 92763.9 1 12.3 O O CR9Y3T9 Nucleolar complex protein 2 homolog 85775.0 O 2.3 O 4.1582 O15355 Protein phosphatase G 59958.1 6 12.3 2 O Na(+)/H(f) exchange regulatory CR 15599 cofactor NE-RF2 36380.6 5 12.3 1 O Q86UY6 N-alpha-acetyltransferase 40 277642 3 12.2 O Platelet-activating factor P684O2 acetylhydrolase 8 subunit beta 257-0.4 3 122 O Phenylalanine-tRNA ligase beta C9NSO9 subunit 66743.0 7 2.2 6 O P3561 Alpha-adducin 78.889.8 5 12.2 6 O Eukaryotic translation initiation factor 3 O5821 subunit G 358962 6 12.2 9 O KH domain-containing, RNA-binding, signal transduction-associated protein O75525 3 3394.86 3 122 7 O P52298 Nuclear cap-binding protein subunit 2 1817.2.2 3 12.2 3 O Probable serine carboxypeptidase C9H3G5 CPV 544.490 4. 12.2 2 O Sarcoplasmiciendoplasmic reticulum O 14983 calcium APase 36.8 13 22 10 O S-adenosylmethionine synthase P3153 isoform type-2 440O2.9 5 2.2 6 O O9NRR5 Ubiquilin-4 63912 7 122 8 O C9Y5X3 Sorting nexin-5 4717 6 12.1 1 O O75083 WD repeat-containing protein 6692.4 9 12. 3 O Peptidyl-prolyi cis-trans isomerase P62942 FKBPA 120078 2 12.0 4. 34929 U3 sma} nucleolar ribonucleoprotein OOC566 protein MPP10 78977.9 7 12.0 5 O P31947 14-3-3 protein sigma 264.7 6 12.0 10 O Phosphatidylinositol-binding clathrin Q13492 assembly protein 7CO23.O. 4 12.0 3 O O96VE7 Zinc finger protein 512 65765.7 8 2.O 2 O C98PU8 Protein quaking 361451 3 120 10 O J3 Small nucleolar RNA-associated O8TEDO protein 15 homolog 58757.5 O 120 9 28377 P2947a. Nitric oxide synthase, endothelial 34942.8 1 2.O 1 O PO404 Catalase 5998.44 9 2.0 2 O Ribose-phosphate pyrophosphokinase P1908 2 353.0 2 12.0 1O O O60488 Long-chain-fatty-acid-CoA ligase 4 77.8958 9 11.9 10 Q6NO3 Putative histone H2B type 2-C 21985.3 4. 19 O O Patent Application Publication Jul. 6, 2017. Sheet 87 of 141 US 2017/0192012 A1

FIG. 7 (cont'd) P49588 Alanine-tRNA tigase, cytoplasmic 107552.O. 11 1.8 6 O P50995 Annexin A11 54732. 8 19 6 O Q6AN6 Caprin-2 98976.8 2 1.9 8 O C9 KA9 Polypyrimidine tract-binding protein 2 53979. 8 119 1O 85.554 Cytochrome c oxidase protein 20 Q5R 5 homolog 14236,6 1 1.9 2 O P5581 Microfibrillar-associated protein 1 51958.5 5 1.9 4 O O05682 CaldeSnon 68838.7 8 118 O O Translation machinery-associated Q96EY4 protein 16 24O924 4. 18 1 O 39S ribosomal protein 48, Q96GC5 mitochodia 2448.9 2 8 2 O U6 snRNA-associated Smi-ike protein P823 O S3 1845.4 3 118 6 43,332 C92542 Nicastrin 7829O.A. 6 11.8 6 O P6108 Ras-related protein Rab-4B 258317 2 11.7 1. O 28S ribosomal protein S14, O60783 mitochondria 5252.8 11.7 O 26S proteasome non-ATPase PA8556 regulatory subunit 8 3989. 5 1.7 O UDP-glucose:glycoprotein Q9NYU2 glucosyltransferase 176.7394 16 1.7 O 1391 Ubiquinol-cytochrome-c reductase O9NWA1 Complex assembly factor 31 6.6 A. 17 3 O PF8316 Nucleolar protein 14 954473 11 1.7 1O O P55854 Small ubiquitin-related modifier 3 11694.1 2 17 1O O C9HR5 SAP30-binding protein 33O837 3 16 2 O P6787O Casein kinase subunit beta 25284. 3 1.8 2 O General transcription factor 3C C9Y5C8 polypeptide 5 59858.3 7 1.6 6 O O8N8S Protein enabled homolog 65.331.5 4. 11.8 2 O O9NP8 Serine-tRNA ligase, mitochondrial 586 12.7 6 18 4 O Dimethyladenosine transferase, C8WWMO || Ocordia 39885.2 3. 11.8 O 39S ribosomal protein 16, O9NX20 mitochondria 235063 2 18 1 O P55196 Afadir t988938 17 | 115 O O C96E7 ERO1-like protein alpha 55.248. 7 15 2 O P61086 Ubiquitin-conjugating enzyme E2K 2252O. 3 15 O Q9NXF1 Testis-expressed sequence 10 protein 105507.5 7 5 O O Ras-related C3boutinum toxin P15153 Substrate 2 2828.0 2 115 2 O Guanine nucleotide-binding protein P29992 subunit alpha- 42408.6 3 14 2 O P621.58 Calmodulin 6837.7 3 14 O 258525 Guanine nucleotide-binding protein Q4344 subunit alpha-13 44398 8 4 3. 7319 POO9 Adrenodoxin, mitochondria 9877.9 1 4 O Serine hydroxymethyltransferase, P34896 cytosolic 494.38.8 8 1.4 O O C32P28 Prolyl 3-hydroxylase 1 82861.6 10 14 9 O C5RKV6 Exosome complex component MTR3 2852O3 3 114 O Q5SS35 Heterochronatin protein -binding 54569.5 8 4. O 4472 Patent Application Publication Jul. 6, 2017. Sheet 88 of 141 US 2017/0192012 A1

FIG, 17 (cont'd) protein 3 O15007 Pre-mRNA-spicing regulator WAP 35562.6 6 14 3 O Putative 40S ribosomal protein S10 O9NO39 like 2O291.5 3 4. 3 O Actin-related protein 23 complex P59998 Subunit 4 4.6758, O 6 113 4. O O92797 Symplekin 125219.4 13 11.3 10 O Q96:37 Putative RNA-binding protein 15 106331.2 9 113 10 O P38432 63292.7 6 11.3 4. O O95470 Sphingosine-1-phosphate lyase 64094.2 7 113 1 O O4G03 La-related protein 7 53009.O 8 11.2 3 O O6O749 Sorting nexin-2 58585.3 8 12 4. O Cytoplasmic dynein 1 intermediate Q13409 chain 2 70430.2 6 11.1 10 O AP-dependent zinc metalloprotease Q96 A2 YME11 80965.9 8 1.1 3 O Polynucleotide 5'-hydroxyl-kinase O5SY 6 NO 9 80577.5 6 11. 8 18987 P26358 DNA (cytosine-5)-methyltransferase 1 175519.3 2O 1.1 10 O O9Y2W2 WW domain-binding protein 11 69997.8 8 11. 4. O O8N98 Protein KR homolog 834 0.3 9 11.1 10 9966 Q96E17 Ras-related protein Rab-3C 26 80.4 4. 110 10 O P2664 Valine-tRNA tigase 141730.8 11 11C 4. 1566O Q9Y27 Y-box-binding protein 2 38575. O 3 110 10 O Peptidyl-prolyl cis-trans isomerase A F5-284 like 4D 18394.9 4. 10 O DNA-directed RNA polymerases , , P 19388 and Subit RPABC1 24665.3 3 10 f O HiA class histocompatibility antigen, P3O499 CW-1 alpha chain 41420 3 10.9 4. O CR520 Protein FAV988 4.1768.3 5 10.9 2 O O9UBF2 Coatomer subunit gamma-2 98763. 9 10.9 2 O P42685 Tyrosine-protein kinase FRK 58710.4 4. 10.9 O Ch92643 GP-anchor transamidase 45537.O 3 O.9 1. O Dihydroxyacetone phosphate O15228 acyltransferase 77986.5 7 10.9 2 O P13674 Proly 4-hydroxylase subunit alpha- 606100 6 10.9 6 O Mitochondria C O3SY69 formyltetrahydrofolate dehydrogenase 85592.5 13 0.8 8 O Q9GZR7 AP-dependent RNA helicase DDX24 96.959.2 6 10.8 2 O Glycylpeptide N P3O419 tetradecanoyltransferase 52758.7 4. 10.8 10 O Proteasomal ubiquitin receptor O16186 AORM 42438.5 6 O.8 2 O NADH dehydrogenase ubiquinone O7525 iron-sulfur protein 7, mitochondrial 2.3848.7 4. 10.8 9 59 140.5 C15833 Syntaxin-binding protein 2 66908.9 6 10.8 O Trafficking protein particie complex O9U33 subunit 2-like protein 16273.2 2 10.8 2 O Chromodomain-helicase-DNA-binding O12873 protein 3 226266.3 21 10.8 1O O Q0559 Serinefarginine-rich splicing factor 11 53592.2 4 10.8 1O 49572 P27707 Deoxycytidine kinase 3O860.8 4. 10,8 O Patent Application Publication Jul. 6, 2017. Sheet 89 of 141 US 2017/0192012 A1

FIG. 17 (cont'd) HLA class histoCompatibility antigen, CO4828 B-40 alpha chain 48847.4 3. O.8 2 O O16762 Thiosulfate sulfur transferase 3.3657.1 2 0.8 4. O Serinefarginine repetitive matrix C8YB3 protein 1 O2287.7 8 0.8 1. 92439 P27,708 CAD protein 2453.223 21 O.7 7 716. HLA class histoCompatibility antigen, C3612 B-73 alpha chain A08344 3 0.7 5 O O8EX9 importin-4 120342. 10 | 10. O 227 .36 P5648 Fatty aldehyde dehydrogenase 56,714.9 4. 10.7 10 O Q9NP72 Ras-related protein Rab-18 23262.2 3 0.7 1 O HLA class histocompatibility antigen, P305O1 CW-2 alpha chain 4494.1 3. 10.7 2 O O7588O Protein SCO1 homolog, mitochondria 34O42.1 3 0.6 1 O OO6787 Fragile X menta! retardation protein 6886O.O 6 O6 10 O P08779 Keratin, type cytoskeleta 16 51610. 5 O6 2 O Q8N34 subtit SA-2 144568.7 16 || 10.6 O O Cleft 3ip and palate transmembrane O96KA5 protein 1-like protein 66062 4. O6 2 O 39S ribosomal protein 18, C9-OU6 hitochondria 20804.7 2 O.6 O Adenylosuccinate synthetase isozyme P30520 2 504966 6 10.5 4. O Malonyl-CoA-acy carrier protein O8WS2 transacylase, mitochondrial 434 17.8 3 0.5 1 O Q9BWS9 Chitinase domain-containing protein A4972.8 4. 0.5 6 O Spliceosome-associated protein C91.3 CWC15 homolog 2668 4 0.5 1 O C92879 CUGBP Elaw-like family member 527023 7 O.5 18 O 2736 Mitogen-activated protein kinase 3 4822.7 3 10.5 8 O AOFGR8 Extended synaptotagnin-2 98.334.8 7 O.4 10 O Nucleoside diphosphate-linked moiety A8/XW4. X motif 19, mitochondria 42575.5 8 1.4 2 O PO7948 Tyrosine-protein kinase lyn 5776O.O. 8 0.4 2 O Q929OO Regulator of nonsense transcripts 125OO23 12 || 0.4 8 O C9696 DNA topoisonerase, mitochondria 6A828.8 8 103 18 O Ch9BV-2 Nucleoporin p58/p45 57048.7 4. 10.3 10 O C9Y389 RRP 5-like protein 3655.3 A. 0.3 1 O Acidic leucine-rich nuclear O43423 phosphoprotein 32 family member C 26933.0 3. O3 A. O 19623 Spermidine synthase 34.395 3 O3 2 O P24447 Akaite nuclease 57785.2 3. O.3 1 O Required for meiotic nuclear division Q9NWS8 protein 1 homolog 520O3.2 6 0.2 O P 2081 Histidine-tRNA ligase, cytoplasmic 556O7.1 9 12 6 O O668 Complement C2 72O74.6 3. O2 3 O Q2800 Alpha-globin transcription factor CP2 54.68. 3 O2 A. O C6XN9 WD repeat-containing protein 82 354783 2 O2 O O9NV2 ADP-ribosylation factor-like protein 8B 2767.2 2 0.2 2 O Q8EC6 Gem-associated protein 5 170927.7 7 102 1 O O969X6 Cirhin 7310.8 7 O.2 O O C13724. Mannosyl-oligosaccharide glucosidase 920888 9. O2 7 O Patent Application Publication Jul. 6, 2017. Sheet 90 of 141 US 2017/0192012 A1

FIG. 17 (cont'd) 28S ribosomal protein S35, P82673 ritochondria 35037.6 2 10. 2 O P33176 Kinesin- heavy chain 10428.4 9 10. 2 O C3SYB3 Forkhead box protein 4-ike 6 48.699.9 3 10. O C6VB84. Forkhead box protein D4-ike 3 48732.9 3 10.1 C9H115 Beta-soluble NSF attachment protein 33899.2 6 10. 4. O Q9UX6 A-kinase anchor protein 8-like 68895.6 5 10.1 2 O Sister chromatid cohesion protein O29RF7 PDS5 homolog A 13741.6 13 10.0 8 O Transmembrane 9 superfamily O9HO45 ninenber 3 68629.8 10.0 9 O C9NUC Ufm 1-specific protease 2 53660.6 7 10.0 1 O NFU iron-sulfur cluster scaffold O9UMSO homolog, mitochondrial 27335,7 4. 10.0 8 296O1 O 1473 Tripeptidyl-peptidase 482265 3. 10.0 4. O Actin-reated protein 23 complex O544 subunit 2 34.447. 4. 10.0 O Q08378 Golgin subfamily. A member 3 154885.8 15 O.O. O 0. Q9NSB2 Keratin, type I cuticular hib4 85983.0 11 10.0 1G O Q9UCRO Sex comb on midleg-like protein 2 78112.3 O O.O. 2 O Pasma membrane calcium P2002 transporting ATPase 13439.1.2 8 10. O O Peptidyl-prolyi cis-trans isomerase C96AY3 FKBP10 64758.4 11 10.0 5 O P1436 Gia fibrillary acidic protein 49967.7 6 10. 10 C96 US Polyadenylate-binding protein 5 43672.9 5 10.0 2 O O5269 Serine palmitoyltransferase 53343 5 9.9 4. 3291.9 O 14654. risulin receptor substrate 4 134794.3 13 9.9 7 O V-type proton ATPase subunit 8, P 533 kidney isoform 57.232.4 4 9.9 O DnaJ homolog subfamily A member 3, CR96EY1 mitochondria 51677.5 4. 9.9 6 O Q13616 Culin-1 90.363.O 8 9.9 2 O rRNAftRNA 2'-O-methyltransferase A6NHQ2 fibrillarin-like protein 34.732.3 2 9.9 43209 Ribosome biogenesis protein BMS1 O4692 homolog 1466.62.9 4 9.9 10 3585 Procoliagen-lysine,2-oxoglutarate 5 CRO2809 dioxygenase 842O6 9.9 5 O Q9BC8 Metastasis-associated protein MTA3 63843.2 8 9.9 10 O O12797 Aspartyilasparaginy beta-hydroxylase 8638.9 7 9.9 2 O O3098 COP9 signatosome complex subunit 1 57.168.4 4. 9.9 9 A6NH2 Tubulin alpha chain-like 3 48426.2 8 9.9 10 O PC25 Phosphoglycerate kinase 2 45954 3 9,8 O Peripheral plasma membrane protein O4936 CASK O4338.9 7 9.8 5 O DNA-directed RNA polymerase P3O876 son RB2 135322.8 4. 9.8 6 O P35749 Myosin-1 226689.3 9 9.8 10 O 39S ribosoma protein L23, Q16540 mitochondria 17781.2 2 9.8 2 0. C8AA5 GrpE protein homolog 2, mitochondrial 257734 4. 9.8 1 O Q9Y6N5 Sulfide:Quinone oxidoreductase, SO245.9 6 9.8 O Patent Application Publication Jul. 6, 2017. Sheet 91 of 141 US 2017/0192012 A1

FIG. 17 (cont'd) mitochondria Lysine-specific histone demethylase O6034 A. 94.542.1 6 9.7 2 O Secretory carrier-associated O1527 membrane protein 2 37105.2 2 9.7 3 O Mannose-P-dolicho utilization defect O75352 protein 26923.0 3. 9,7 3 O Cleft lip and palate transmembrane O96805 protein 1 76324.9 5 9. 1 O Q13619 Cullin-4A 82735.5 10 9.7 2 O Q86YPA Transcriptional repressor p36-alpha 66986.4 5. 9.7 4. O transmembrane emp24 domain O3445 containing protein 1 25376.9 2 9.7 1 O Q96S52 GP transamidase component PG-S 64450 3. 9.7 6 O Q8NFW8 N-acylneuraminate cytidylyltransferase 49063.6 A. 9.7 4. O Q96EK5 KF-binding protein 72498.5 5 9.7 2 O Q96ST3 Paired amphipathic helix protein Sin3a 459.737 9 9.7 3 O C9BTD8 RNA-binding protein 42 481524 3 96 4. O RNA polymerase-associated factor Q8N 7-5 honolog 57735.5 5 9.6 2 O Q9C88 Cyclin-dependent kinase 1A 76617.0 5 9.6 6 O Hepatoma-derived growth factor Q774V5 related protein 2 7A4444 6 9.6 6 47855 P46063 ATP-dependent DNA helicase Q1 74484.O. 7 9.6 2 O Q68OR7 2',5'-phosphodiesterase 12 63919.2 5 9.5 2 O Q9NZ7 Upstream-binding protein 59.937.7 5. 9.5 4. O O9UNE7 E3 ubiquitin-protein ligase CHP 31361.O 3 9.5 2 O P14373 Zinc finger protein RFP 5076.6 8 9.5 2 O Dynamin-like 20 kDa protein, O60313 mitochondria 114328.0 9.5 8 O large neutral amino acids transporter

OO 650 Sna subunit 1 55694.7 3 9.5 2 O C96G23 Ceramide synthase 2 44990.3 2 9.5 O KH domain-containing, RNA-binding, signal transduction-associated protein Q5WWX 2 38927.4 3 9.5 4. O inactive hydroxysteroid C3SXM5 dehydrogenase-like protein 34.330.6 2 9.5 2 O p21-activated protein kinase O9NW interacting protein 44534.2 3. 94. 2 O Cytochrome c oxidase assembly Q9Y2RO protein 3 homolog, mitochondrial 1733 2 9.4 1 O HA class histocompatibility antigen, P3O4.86 B-48 alpha chain 4O743 2 9.4 3. O P8 160 Actin-related protein 2 45169.2 5 9.4 5. O Q15437 Protein transport protein Sec23B 874.488 7 9.4 3 O HLA class histocompatibility antigen, Q3610 B-81 alpha chain 4O742.3 2 9.4 3 O O7KZ85 ranscription elongation factor SPT6 20032.6 17 9.4 4. O Q8X1 Mitochodria Rho GPase 2 53997.8 4. 9.4 3. O C9NCZ2 Something about silencing protein 30 54.672.1 3 9.4 1 O P19022 Cadherin-2 OO265.7 7 9.4 8 O ATP-dependent RNA helicase C9UMR2 DDX19B 50847.4 3 9.4 7 O Patent Application Publication Jul. 6, 2017. Sheet 92 of 141 US 2017/0192012 A1

FiG. 17 (cont'd) Fragile X mental retardation P516 syndrome-related protein 2 74565.6 7 9.4 3 O O98E1 Oynactin subunit 5 206968 4 93 O O9 MY Nucleolar protein 7 29.483.5 3 9.3 3 O POCG38 POTE ankyrin domain family member 122936.4 2 9.3 10 O Eukaryotic translation initiation factor O98Y44. 2A 65560.5 7 92 2 O PO4259 'Keratin, type : cytoskeletal 6B 60352.2 8 9.2 10 4242 CAMP-dependent protein kinase type P 644 -alpha regulatory subunit 43209.9 3 9.2 O P484.49 ilanosterol synthase 8788.8 8 9.2 8 O O9R3 Protein phosphatase 1H 58964 7 91 2 O O9Y2J2 Band 4.1-like protein 3 109251.6 9 9. 2 O hA class histocompatibility antigen, PO3989 B-27 alpha chain 40827.4 2 9.1 O H: A class histocompatibility antigen, P3O461 B-13 alpha chain 40816.5 2 9. 1 O H: A class histocompatibility antigen, P3O481 B-44 alpha chain 40823.5 2 9. 1 O H.A class histocompatibility antiger, P3O483 B-45 alpha chain 4O699.3 2 9.1 1 O H: A class histocompatibility antigen, P30485 B-47 alpha chain 493.6 2 9. HiA class histocompatibility antigen, P304.87 B-49 alpha chain 408666 2 9.1 1 O hi A class histocompatibility antigen, P3O488 B-50 alpha chain 408265 2 9, 1 1 O Pumilio domain-containing protein O15397 KAAO02O 73983.8 6 9.1 3. O O75150 E3 ubiquitin-protein ligase BREB 108589.8 10 9.1 4. O C93B9 Tuftelin-interacting protein 11 97.219.2 7 9.1 2 O OOO159 Unconventional myosin-ic 12O556.5 13 9.1 6 O O9AV4. Exportin-5 13842.5 15 9. 4. O ATP-dependent RNA helicase O8YB8 SUPW3, mitochondria 88846.8 8 9.O. 6 O Nuclear pore complex protein Nup98 P52948 Nup96 169 16.8 17 9.0 10 O Procotagen-ysine,2-oxoglutarate 5 OOO469 dioxygenase 2 86833.5 6 90 4. O C4VX2 Polyadenylate-binding protein 1-like 69019.7 9 9.0 1. O MOSC domain-containing protein 2, O969Z3 mitochondria 38593.7 7 9.0 O BRCA2 and CDKN1A-interacting O9P287 protein 3632.7 4 8.9 1 O O5UPO Telomere-associated protein RF1 275216.5 19 8.9 O 19788 Plasma membrane calcium P23634 transporting ATPase 4 3229 9 8.9 10 O P49750 YLP notif-containing protein 1 2284.18. 16 8.9 8 O C15436 Protein transport protein Sec23A 87073.4 7 8.9 6 O O92922 SWI/SNF complex subunit SMARCC 123380.5 16 8.9 9 O OOO181 Synaptosomal-associated protein 23 2O885.2 1 8.9 4. O P17540 Creatine kinase S-type, mitochondria 48017.8 5 8.8 1. O G protein-activated inward rectifier PA8544 potassium channel 4 48.810 2 8.8 O Patent Application Publication Jul. 6, 2017. Sheet 93 of 141 US 2017/0192012 A1

FIG. 7 (cont'd) P8O303 Nucleobindin-2 5O312.4 3 8.8 6 O O8WXFO Serinefarginine-rich spicing factor 12 30683.0 3 8.8 10 O ATP-dependent RNA helicase Q9NUU 7 DDX19A 5443.4 4. 8.8 2 O Pyruvate dehydrogenase protein X OOO330 component, mitochondrial 5.435.8 4. 88 2 O ATP-binding cassette sub-family B O75O27 member 7, mitochondrial 82990.7 5 8.8 2 O Q7.277 Protein zer-1 homolog 895.38.3 5 8.8 1 O Ch9996 Endophilin-A2 39096.6 3 8.8 2 O FAD-dependent oxidoreductase O96CU9 domain-containing protein 45829, 5 8.7 3 O Probable histidine--tRNA ligase, P49590 nitochondria 57629.8 4. 8.7 3 O tyrosine-protein phosphatase non OO624 receptor type 11 636O4.9 3 8.7 3 O O5382 GTP-binding protein Rheb 2O5546 8.7 O O42O3 Dynactin subunit 349.99.3 12 8.7 1O O P2O337 Ras-reated protein Rab-3B 24986. 2 8.7 1O O O96FV9 HO complex subunit 1 764O7.8 6 8.7 O Rho-related GTP-binding protein P62745 Rhos. 22579.6 1. 8.7 8 O P21 27 Cyclin-dependent kinase B 76517.2 4. 8.7 O O Q5VZ.5 Zinc finger MYM-type protein 4 167303.5 2 8.7 6 O O4776 Transcription elongation regulator 1 122995.5 4. 8.6 10 50586 P2O336 Ras-related protein Rab-3A 2522. 2 8.6 O O FAST kinase domain-containing O9NYY8 protein 2 789 .9 7 8.6 A. O Putative 60S ribosomal protein 37a A8NK-3 like 10867.8 1 8.6 2 O O43583 Density-regulated protein 2249.2 1 8.6 O POTE ankyrin domain family member POCG39 18815.9 10 8.6 1O O O969V3 Nicai 63085 7 85 10 O P84.62 Giucosylceramidase 5913.3 3 85 2 O interferon-induced, double-stranded P19525 RNA-activated protein kinase 6O1988 5 85 2 O P35527 Keratin, type cytoskeletal 9 62292.5 3 85 1 O P53992 Protein transport protein Sec24C 19864.7 9 85 4. O Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha P631.51 isoform 52859.2 4. 8.5 2 O Q9Y4P3 transducibeta-like protein 2 50425.2 O 85 1 O Probable ATP-dependent RNA O9NY93 helicase DX56 5983 3 5 8.5 8 2C968.5 O96S66 Chloride channel CLC-like protein 51989,9 5 8.5 A. O O9 BW8 Pefir 30666, 3 8.5 3 O Electron transfer flavoprotein ubiquitone oxidoreductase, O 634. nitochondria 69293.9 5 8.4 1 O P4996 DNA ligase 3 11157.6 12 8.4 1O O Probable leucine-tRNA tigase, Q503 Ocondia 102888.8 3 8.4 4 O Patent Application Publication Jul. 6, 2017. Sheet 94 of 141 US 2017/0192012 A1

FIG. 17 (cont'd) C9-OPO Cytosoic 5'-nucleotidase 3A 34577.3 3 8.4 4. O ranslocase of inner mitochondrial membrane domain-containing protein Q9MP8 1 32343.9 4 84 O immunoglobulin-like and fibronectin O86WF2 type it domain-containing protein 1 385972.8 42 | 84 7 O Probable E3 ubiquitin-protein ligase Q9000 rakorir-2 A83.09.0 3. 84 ? Q8WYA6 Beta-catenin-like protein 51084.3 8 8.4 7 28428 O928.78 DNA repair protein RAD50 49922 13 8.4 10 O CR 14160 Protein scribble honolog 73853.4 12 8.3 7 O P12036 Neurofilament heavy polypeptide O9287.2 7 8.3 O 889.5 Potassium-transporting At Pase alpha P206A8 chain 15829.9 7 8.3 5 O Dehydrogenaselreductase SDR family Q6ANO member 7B 35.404.2 3. 83 O C95453 Poly(A)-specific ribonuclease PARN 89743.5 4 83 3 P2242O Regulatory protein E2 5592.1 8 8.3 1 O O 15904 V-type proton ATPase subunit S1 5297.8 4 8.3 1 O Small subunit processome component O7569 20 homolog 32.1009.2 27 | 8,3 9 6 52 Structra mainterance of chromosomes flexible hinge domain A6NHR9 Containing protein 2O7595.3 14 8.3 9 O OR 14562 ATP-dependent RNA helicase DHX8 4.0170.2 13 8.3 3 O Ankyrin repeat and sterie alpha motif O26G8 domain-containing protein 1B 139321.0 8 83 1 O O8XKO Polyhorneotic-like protein 2 30452.4 3 8.2 4 O C00526 Cyclin-dependent kinase 3 3559.9 2 8.2 4. O C99.426 tubulin-folding cofactor B 2760.7 2 8.2 O P 0253 Lysosomal alpha-glucosidase 106.1794 8 8.2 2 O P5289 Hexokinase-2 O385.8 13 8.2 7 O 28S ribosomal protein S15, P8294 ritochondria 29956.2 3 8.2 1 O CR8NF-3 Nucleoporin Nup43 a26O7. 2 8.2 3 O L-2-hydroxyglutarate dehydrogenase, C99P8 ritochondria 50237.7 8 8.2 2 O Probable ATP-dependent RNA C9NOO he case DDX4 73841.8 7 82 O O O982 SUMO-activating enzyme subunit 2 1794. 7 8.1 3 O C9Y5A9 YTH domain family protein 2 59776.9 5 8.1 4. O RANBP2-like and GRP donnair PCBO containing protein 1981448 14 8. 4. O60229 Karir 21 1910.6 21 8. 5 O5APR3 CD276 antigen 56424.2 3 8. 1C O Structural maintenance of O9534 chronosories protein 2 130776.2 9 8. 8 O RANBP2-ke and GRP domain PO), Containing protein 2 1987.90.6 14 8. 4. O CR98YPF Serine/threonine-protein kinase WNK3 94128.7 12 8. 2 O ATP-dependent Cip protease ATP binding subunit cipX-like, O7603 rtochondria 69985.2 8 8. 7 17778 C9NERPO Oligosaccharyltransferase complex 16943.4 1 8. 6 598.08 Patent Application Publication Jul. 6, 2017. Sheet 95 of 141 US 2017/0192012 A1

FIG. 7 (cont'd) sount OSC WD repeat and FYWE domain Q8W87 containing protein 47350.3 2 8.1 1 O O75323 Protein NipSnap homolog 2 3390.8 4. 8.0 O O43790 Keratin, type it cuticular Hb6 55545 6 8.0 9 O CR 16352 Alpha-internexin 555618 6 8. O Splicing regulatory glutamirelysine O8WXA9 rich protein 1 687248 4. 8.0 A. O Q8N056 Protein SM14 homolog A 5O770.0 6 8. 4. O Centromerefkinetochore protein zw10 O43264 homolog 89885. 4 8. 1 O P78385 Keratin, type cuticular b3 55963.3 5 7.9 10 O C.9999.6 A-kinase anchor protein 9 44.3504.3 36 7.9 O O Cytoplasmic FMR1-interacting protein 576 * 14.047.5 7.9 6 O O3112 Chromatin assembly factor 1 subunit 8 61948.8 8 7.9 2 O Sarcoplasmic/endoplasmic reticulum C93084 calcium ATPase 3 1385.3 8 7.9 1O O C14789 Golgin subfamily B member 378O340 40 7.8 O O O4.3747 AP-1 complex subunit gamma- 92392.8 7 7.8 4. O O6NUC4 Transmembrane protein 214 76422. 5 7.8 4. O P83876 hioredoxin-like grotein 4A 16900.5 t 7.8 2 O POCG48 Polyubiquitin-C 77038.7 6 7.7 O O PO7686 Beta-hexosaminidase subunit beta 63567.8 6 7.7 4. O O8NB5 ProcoBagen galactosyltransferase 71.978.4. 6 7.7 2 73O4. Procoliagen-lysine,2-oxoglutarate 5 OSO568 dioxygenase 3 85355.6 5 7.7 2 7053 O4533 Keratin, type cuticular Hib? 56867.3 6 7.7 9 O Q15021 complex subunit 158608.1 8 7.7 3. O Mesencephalic astrocyte-derived P5545 neurotrophic factor 21:56.4 7.7 2 O Transmembrane 9 superfamily C.9985 member 2 76859.3 3 7.7 O Keratin, type H cytoskeletal 2 P35988 epiderina 6578. 8 7.7 8 33 16.7 P 13796 Pastin-2 7O858.8 8 7.7 10 O Q982O Crooked neck-like protein 1 94.662.2 1 7.7 O O Fragile X mental retardation P514 syndrome-related protein S3819.8 5 7.7 3. O Q53F19 Uncharacterized protein C17orf85 54.813.5 5. 7.7 4. O Cytoplasmic dynein 1 tight Q9YSG9 interediate chain 56864.4 7 7.7 O Basic leucine zipper and W2 domain CR9Y6E2 containing protein 2 48390.6 6 76 7 O Transmembrane 9 superfamily O92544 member 4 75260.3 4 7.6 2 O Q7Z406 Myosin-14 27862.7 22 7.6 O RANBP2-ke and Grip corai O A75 containing protein 8 200304.8 3 7.6 6 O Q9GZR2 RNA exoticease 4 46900.0 2 7.6 1 O Transiocon-associated protein subunit O9 JN-2 ganna 2030.5 3 7.6 O 63744 P43O34 Patelet-activating factor 47208.3 6 7.6 2 O Patent Application Publication Jul. 6, 2017. Sheet 96 of 141 US 2017/0192012 A1

FIG. 7 (cont'd) acetylhydrolase IB subunit alpha PO7864 -actate dehydrogenase C chain 36653.5 A. 7.5 O O Q8TAC2 SWI/SNF complex subunit SMARCC2 28339.9 1 7.5 10 O G8N2O7 Protein unc-80 homolog 2O946 O 6 7.5 A. O Tyfosine-protein phosphatase non P54829 receptor type 5 62670.6 3. 7.5 2 O Q3620 Cir-AB 97.37.4 12 || 7.5 6 O POC88 Radial spoke head 10 honolog B O1319.4 7 7.5 1 O Q6JWP7 lysocardiolipin acyltransferase 43555.7 3. 7.5 3 O Phosphatidylinositide phosphatase C9Y2H2 SAC2 867966 3. 7.5 2 O Q9877 Regulator of nonsense transcripts 3B 5708 4. 7.5 A. O O14787 Transportin-2 O2349.O 5 74 1. O PO7602 Prosaposin 8O142.5 3 7.4 3 O Q02539 histore -. 21842.1 3 7.4 18 O CZ794 Keratin, type 3 cytoskeleta 1 b 62.86.6 8 4. 6 O Putative cytochrome b-c1 complex

POC7P4 subunit Rieske-like protein 3 OO6 2 7.4 4. O Q96MM3 Zinc firger protein 42 honolog 35.543.2 2 74. 1 O C9H2F5 Enhancer of polycomb honolog 1 9:309.6 5 7.4 4. O CO1658 Protein 1 196718 7.4 1 O N-alpha-acetyltransferase 15, NatA Q98X9 auxiliary subunit 891.89.7 9 74. 9 O HA class histocompatibility antigen, PO4222 CW-3 alpha chain 4,260.0 2 7.4 2 O P78386 Keratin, type cuticular Hb5 573419 7 7.3 1. O O9Y2K3 Myosin-15 226045.0 22 || 7.3 1 O 3561 Stero O-acyltransferase 1 62. 14.6 4. 7.3 9. O Plasma membrane calcium Q1672O transporting ATPase 3 29.188.9 7 7.3 8 O S1 RNA-binding domain-containing CR8N5C6 protein 98.9147 1O 7.3 3. O P51532 Transcription activator BRG1 82634.7 5 7.3 1. O Q96G8 Target of EGR1 protein 57403.3 3 7.3 O Guanine nucleotide-binding protein P504.8 G(d) subunit alpha 424,273 2 7.2 1 O Q98CO)4 RNA-binding protein 48 4O49.9 4. 7.2 3. O 9NWA2 Septin-11 558.4 4. 7.2 3 O Probable ATP-dependent RNA CR 13208 helicase DDX10 O1230.3 7 7.2 2 O Q9NRZ9 Lymphoid-specific helicase 9,212.5 9 7.2 O O Eukaryotic translation elongation O43324 factor epsilon-1 17707. 1. 7.2 2 2543.7 Sister chromatid cohesion protein Q9NT5 PDS5 homolog B 62728.7 9 7.2 10 5787 Zinc finger Ran-binding domain O952.18 containing protein 2 373.17.6 5 7.2 6 O O96SB4 SRSF protein kinase 1 84O9.6 4. 7.2 2 O Putative uncharacterized protein Q62OTO F45035 682.7 2 7.1 1 O Q9936 Mitochondrial glutamate carrier 34926.5 3. 7. 1 O POO45 Coagulation factor Will 268492.6 7 7.1 2 O Patent Application Publication Jul. 6, 2017. Sheet 97 of 141 US 2017/0192012 A1

FIG. 17 (cont'd) Ona homolog subfamily C member Q9NVH1 11 60253.2 4. 7. 5 O Dihydroorotate dehydrogenase CO2 127 (quinone), mitochondria A28673 3 7.1 O C8N392 Rho GTPase-activating protein 18 5262.0 3. 7.1 1 O MMS19 nucleotide excision repair Q96T76 protein honolog 1359.9 8 7.1 5 O O4325 RNA binding protein fox-honolog 2 42.58.0 3 7.1 O 36063 Chronodomain-helicase-DNA-binding O 14646 protein 197779.8 10 || 7.1 6 O C9HC-5 Synaptotagmin-like protein 2 40.359.2 8 7.1 3 O J3 Small nucleolar RNA-associated CSAP6 protein 14 honolog C 87302.0 A. 7.1 8 O OC506 Serine threonine-protein kinase 25 48339.8 3. 7.O 1 O915 Transgelin-3 22643.8 2 7. t O 9NWB RNA binding protein fox-li honolog 42493.7 3 7. O O O9YAW6 AFG3-like protein 2 89.04. 12 70 2 O tRNA pseudouridine synthase A, Q9Y608 ritochondria 46A65.5 3 7.0 2 O CR 133O8 inactive tyrosine-protein kinase 7 12380.4 10 || 7.O O O O659C4 a-related protein 18 63824.4 7 7.0 6 O O6PKGO La-related protein 12O387.O 8 7.O 4 8 Tumor suppressor p53-binding protein CR 12888 25899.O 15 || 7.0 O O Calcium-binding and coiled-coil Q9PZ2 domain-containing protein 75592.2 4. 7.0 3. C O8WWMF Cohesin subunit SA- 145397.1 14 || 6.9 4. O Phosphoenolpyruvate carboxykinase, P35558 cytosolic GTP 699.93.1 6 6.9 3 O O93N75 Protocadherin alpha-12 102279.4 6 6.9 1 O Rare 2-like arc GRP connair O723.3 containing protein 4 198776 6.9 4 O DNA-directed RNA polymerase ill O9NWO8 sort RPC2 1259926 6 6.9 2 O Nuclear distribution protein nudE Q9NXR1 homolog 1 38378.4 3 6.9 2 O Ceavage and polyadenylation Q10570 specificity factor subunit 1 16238.7 3 || 6.9 6 O C.4008 Cytoskeleton-associated protein 5 225.361 16 5.9 O O High affinity cationic amino acid P3O825 transporter 684939 4. 6.8 3 O Brain-specific angiogenesis inhibitor 1 Q9UQB8 associated protein 2 58361.2 5 6.8 6 O DnaJ homolog subfamily C member Q8X31 18 898.62.6 7 6.8 2 O Putative pre-mRNA-splicing factor O6023 ATP-dependent RNA helicase DHX16 199481 9 8.8 5 O CR9GZN1 Actin-related protein 6 A6266.4 4. 6.8 O O 15049 NEDD4-binding protein 3 60928. 3. 6.8 1 O C9NW Fanconi anemia group protein 1474.25.8 10 || 6.8 4 O P 14735 insulin-degrading enzyme 18767.1 1 6.8 2 O P2955 Xaa-Pro dipeptidase 5279.4 3. 6.8 3 O O4966 Zinc finger protein 638 170500 13 8.8 1.O. O PO863 Tyrosine-protein kinase CK 58876.9 5 6.8 4 O Patent Application Publication Jul. 6, 2017. Sheet 98 of 141 US 2017/0192012 A1

FIG. 7 (cont'd) Echinodern microtubule-associated O05BV3 protein-like 5 192286 O 6.8 8 O Sarcosine dehydrogenase, C912 mitochondrial O2O064 7 6.8 1 O O98/7 7-dehydrocholestero reductase 55230.9 4 6.7 2 O CR 4677 Clathrin interactor 89 2.2 6 8.7 5 8 Brefeldin A-inhibited guanine O9Y66 nucleotide-exchange protein 2O995 17 6.7 2 O Leucine-rich repeat-containing protein O8N1 G4 47 64043.3 6 6.7 2 O General transcription factor 3C Q9JKN8 polypeptide 4 9.3294. 9 6.7 1 O9JWO Targeting protein for Xk.p2 86280.5 10 6.7 2 O Glycypeptide N O60551 tetradecanoyltransferase 2 57322.5 3 66 2 CR 13769 THO complex subunit 5 homolog 79249.3 6 6.6 3 HLA class histocompatibility antigen, CRO960 A-80 alpha chain 41076.9 1. 66 1 C9HCD5 Nuclear receptor coactivator 5 65764.7 6 6.6 4. O O8N157 Jouberin 130 124.8 12 6.6 2 O Trinucleotide repeat-containing C3NOW7 6A protein 201736.4 1. 6.6 4 O C9H6R4. Nucleolar protein 6 1150542 9 6.6 10 O C3KSU Protein BOLF1 133256.5 9 6.5 2 O Regulation of nuclear pre-mRNA O5W52 domain-containing protein 2 154284.3 1O 6.5 9. O P.11216 Glycogen phosphorylase, brain form 97.380.5 1 6.5 4 O O4651 Plastin-1 7O652.8 8 6.5 6 8 Q9NWO6 DDB - and CU4-associated factor 3 52O29.6 A. 6.5 2 O SO2O Spectrin beta chain, non-erythrocytic 2 271299.9 23 6.5 10 O60885 Bromodomain-containing protein 4 1167974 6 6.5 6 O O8688 Protein polybrono-1 186816.0 14 6.5 O O P50336 Protoporphyrinogen oxidase 51226 3 6.5 0. C96ST2 Protein WS1 homolog 2447.9 3. 65 3. O Dolichy-phosphate beta O9Y673 glucosyltransferase 371743 7 8.5 O Squamous celi carcinoma antigen C5O2O recognized by -cells 3 110790. 9 8.4 3 O Probabie ATP-dependent RNA C9H2U he case OX36 114373.8 7 6.4. 5 AiP-binding cassette sub-family F Q9 JG63 member 2 7 1860.7 8 64 4. 292 Putative high mobility group protei POC6E5 B3-like protein 21371.4 2 64 6 8 Probable global transcription activator P51531 SNF22 18O879.4, 11 6.4 O 8 QO1955 Cottagen alpha-3(V) chain 143482. 10 64 8 P02538 Keratin, type I cytoskeleta 6A 60330.2 8 6.4 10 C P4.8668 Keratin, type I cytoskeleta 6C 6031 O2 6 6.4. 9 P57737 Coronin-7 10688.7 5 8.4 1 O OO2952 A-kinase anchor protein 12 185290.8 12 6.4 9 O P2489 Alpha-crystatin A chain 20023.4 2 6.4 O O60684 importin subunit alpha-7 6O771.0 6 8.3 4 O Patent Application Publication Jul. 6, 2017. Sheet 99 of 141 US 2017/0192012 A1

FIG. 7 (cont'd) Calcium-binding mitochondrial carrier O75746 protein Aratar 7516.2 6 6.3 7 O C68DA Forn- 58889, 9. 6.3 1 O C9H254 Spectrin beta chain, non-erythrocytic 4 254O27.4 22 6.3 9. O Eukaryotic translation initiation factor 4 P8344 gamma 2 OO695 7 6.3 2 O Q8WWK9 Cytoskeleton-associated protein 2 77557.1 7 6.3 1 O O9N22 Midasin 6384:09.5 a 6.3 10 7385 C9YSO Transportin-3 O48116 4. 6.3 4 O O99549 M-phase phosphoprotein 8 97922.8 5 6.3 2 O Serine/threonine-protein kinase PRP4 Q3523 honolog 17329.2 8 6.3 5 O O43663 Protein regulator of cytokinesis 672883 4. 6.3 1 O C8NG3 Protein CASC5 24564.09 19 6.2 6 O P46379 large proline-rich protein BAG6 14596.3 6 6.2 O O O5291 Retinoblastoma-binding protein 5 57796.7 5 6.2 4 O POCO-5 Complement CA-B 94.295 10 6.2 2 O O60831 PRA family protein 2 96.OO1 1 6.2 1 O Guanine nucleotide-binding protein P1652O G()/G(S)/G(T) subunit beta-3 38 90.7 4. 6.2 1 O O9COB2 Uncharacterized protein KAA175 87583.2 8 6.2 1 O TOX high mobility group box family O94.842 enber 4 66594.2 5 6. O Q5RA6 Melanoma inhibitory activity protein 3 211216.3 18 6. 10 O Q9NZW5 MAGUK p55 subfamily member 6 614.02.2 5 6. 4 O C8N4C8 Ninein 225236.6 21 6. 10 O O8WWM7 Ataxin-2-like protein 10973.5 6 6. O O Putative nascent polypeptide associated complex subunit alpha-like O9BZK3 protein 23.306. 1 6. 7 O Putative Rab-43-like protein ASNO38 ENSPOOOOO33071. 20438.O 2 S. 1O O C5W5 Myomesin-3 00487.8 5 6. 2 O P.12883 Myosin-7 22.3896. 4 6.1 2 O isocitrate dehydrogenase NADP O75874 cytoplasmic 4694.45 4. 6.O. O O43592 Exportin-f 11219, 6 S.O. 1 O C96FN4. Copie-2 618743 6 S.O. 7 O Very long-chain specific acyl-CoA P49748 dehydrogenase, mitochondrial 70857.9 4. 6.0 6 O Q7Z3ZO Keratin, type cytoskeleta 25 a98883 6 6.O. 2 O A7E2Y1 Myosin-7B 2225286 A 6.O. 4 O RANBP2-like and GRP dornan C99666 containing protein 56 52298.1 10 60 1) O Microtubule-associated O60307 serine? threonine-protein kinase 3 43935.9 6 6. 1 O O5 F2 Protein SOGA3 O3546 O 5.9 1 O P36268 Gamma-glutamyltranspeptidase 2 61588.6 4. 5.9 2 O CR9YSY8 SEC23-interacting protein O882.6 8 5.9 5 O P25440 Bromodomain-containing protein 2 9036.9 5. S.9 6 O Rae 2-3ke and GRP donair A6MK7 containing protein 3 98.855.9 11 5.9 4 O