Phosphosignature Predicts Dasatinib Response in Non-small Cell Lung Cancer

Name: Work Video:
Duration: 3 min 30 s
Martin Klammer; Marc Kaminski; Alexandra Zedler; Felix S. Oppermann; Stephanie Blencke; Sandra Marx; Stefan C. Müller; Andreas Tebbe; Klaus Godl; Christoph Schaab
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439], 'new': [216, 441], 'path': [217, 442], 'discovering': [219, 444], 'molecular': [220, 445, 521, 557, 584, 749, 784, 1077, 1083], 'markers': [221, 446, 558, 571, 733, 753, 785], 'prediction.': [224, 449], 'introduction': [451], 'targeted': [453, 477, 549, 1703], 'treating': [456], 'major': [460], 'biomedical': [461], 'achievement': [462], 'past': [465], 'decade': [466], '(1Katzel': [467], 'J.A.': [468, 643, 4129], 'Fanucchi': [469], 'M.P.': [470], 'Li': [471, 824, 1684, 1878, 2549, 2713, 2832], 'Z.': [472, 1287], 'Recent': [473, 878], 'advances': [474, 879], 'novel': [476], 'cancer.J.': [483, 852, 1470], 'Hematol.': [484], 'Oncol.': [485, 711, 854, 1472], '2009;': [486, 988, 1307, 1966, 2637, 2801, 2920], '2:': [487, 1714], '2Crossref': [488], 'PubMed': [489, 511, 715, 801, 858, 966, 991, 1007, 1066, 1093, 1139, 1252, 1310, 1373, 1476, 1716, 1969, 2145, 2640, 2804, 2923, 3615, 4239, 4261, 4298], 'Scopus': [490, 512, 802, 859, 967, 992, 1008, 1067, 1094, 1140, 1253, 1311, 1374, 1477, 1717, 1970, 2146, 2641, 2805, 2924, 3616, 3810, 4262, 4299], '(58)': [491], 'Google': [492, 514, 658, 716, 804, 861, 969, 994, 1010, 1069, 1096, 1142, 1255, 1313, 1376, 1479, 1719, 1972, 2148, 2643, 2807, 2926, 3618, 3812, 4240, 4264, 4301], 'Scholar,': [493, 659, 805, 970, 995, 1070, 1314], '2Reichert': [494], 'J.M.': [495, 673, 839, 4147], 'Valge-Archer': [496], 'V.E.': [497], 'Development': [498], 'trends': [499], 'monoclonal': [501, 692], 'antibody': [502, 693], 'therapeutics.Nat.': [504], 'Rev.': [505, 985], 'Drug': [506], 'Discov.': [507], '2007;': [508, 798, 855, 1370, 4295], '6:': [509, 1308], '349-356Crossref': [510], '(330)': [513], 'Scholar).': [515, 717, 862, 1011, 1097, 1256, 1377, 1480, 2149, 4088, 4413], 'Because': [516, 2429, 3700], 'selectively': [519], 'block': [520], 'pathways': [522, 1039, 1075, 1751, 1776, 4244], 'typically': [525], 'overactivated': [526], 'tumor': [528], 'cells,': [529], 'they': [530], 'more': [532], 'precise': [533], 'chemotherapeutics.': [539], 'However,': [540, 718], 'although': [541], 'many': [542, 551], 'therapy,': [550], 'others': [552], 'do': [553], 'not.': [554], 'Therefore,': [555], 'needed': [560], 'therapy.': [569], 'Such': [570], 'facilitate': [573], 'personalization,': [575], 'where': [576, 1019, 1769], 'selected': [578, 1631, 1986, 2234, 2276, 2526, 3510, 3567, 3660, 3676, 3750], 'based': [581, 598, 758, 1960, 2631, 2795, 2914], 'Predictive': [589], 'tests': [590], 'currently': [591, 1380], 'clinic': [595], 'frequently': [597], 'one': [600, 1409, 1795, 1805, 2435, 3838], 'particular': [601], 'linked': [606], 'drug': [609, 1792, 1953, 2624, 2788, 2907], 'target.': [610], 'known': [613], 'example': [614], 'test': [618, 3990, 4052], 'assessing': [620], 'HER2/neu': [621], 'overexpression': [622], 'using': [623, 2076, 2091, 2342, 3197, 3284, 3321, 3587], 'immunohistochemistry': [624], 'fluorescent': [626], 'situ': [628], 'hybridization': [629], 'with': [636, 849, 1399, 1407, 1466, 1707, 1756, 1977, 1981, 2095, 2285, 2314, 2438, 2531, 2966, 3099, 3147, 3204, 3227, 3295, 3370, 3451, 3842, 4010, 4326, 4420, 4433], 'trastuzumab': [637], '(Herceptin®;': [638], 'Roche)': [639], '(3Ross': [640], 'J.S.': [641], 'Fletcher': [642], 'HER-2/neu': [644], '(c-erb-B2)': [645], 'gene': [646, 760, 1508, 1543], 'cancer.Am.': [651], 'J.': [652, 813, 819, 821, 827, 829, 1114, 1129, 1238, 1247, 1291, 1330, 1352, 1691, 1873, 1915, 1925, 1937, 2544, 2586, 2596, 2608, 2708, 2750, 2760, 2772, 2827, 2869, 2879, 2891, 3594, 3787, 4107, 4111, 4125, 4207, 4276, 4282], 'Clin.': [653, 710, 853, 1248, 1471, 1964, 2635, 2799, 2918], 'Pathol.': [654], '1999;': [655, 712], '112:': [656], 'S53-S67PubMed': [657], '4Cobleigh': [660], 'M.A.': [661, 4105], 'Vogel': [662], 'C.L.': [663, 4167], 'Tripathy': [664], 'D.': [665, 1318, 1683, 1879, 1889, 1919, 2550, 2560, 2590, 2714, 2724, 2754, 2833, 2843, 2873, 4169, 4183, 4280], 'Robert': [666], 'N.J.': [667], 'Scholl': [668], 'S.': [669, 677, 772, 1322, 1326, 1662, 1893, 1897, 2564, 2568, 2728, 2732, 2847, 2851, 4119, 4155, 4177, 4248], 'Fehrenbacher': [670], 'L.': [671, 825, 1440, 1685, 1913, 1927, 2584, 2598, 2748, 2762, 2867, 2881, 4141, 4205, 4272], 'Wolter': [672], 'Paton': [674], 'V.': [675, 1336, 4189, 4211], 'Shak': [676], 'Lieberman': [678], 'G.': [679, 811, 1289, 1338, 1348, 1356, 1921, 2592, 2756, 2875, 3785], 'Slamon': [680], 'D.J.': [681, 1458], 'Multinational': [682], 'efficacy': [686], 'safety': [688], 'humanized': [690], 'anti-HER2': [691], 'women': [695], 'who': [696], 'have': [697, 897, 917], 'HER2-overexpressing': [698], 'metastatic': [699, 708], 'has': [703, 1777], 'progressed': [704], 'after': [705, 2337, 2963], 'chemotherapy': [706], 'disease.J.': [709], '17:': [713], '2639-2648Crossref': [714], 'some': [720], 'cases': [721], 'expression': [723, 761, 2133], 'mutational': [725], 'status': [726], 'target': [729, 3495, 3519], 'other': [731], 'singleton': [732], 'might': [734], 'not': [735], 'be': [736, 1779, 3921, 4040], 'therapeutic': [741, 1086], 'response.': [742], 'Recently,': [743, 1392], 'several': [744], 'studies': [745], 'tried': [746], 'identify': [748, 1557], 'multiple': [752, 4056, 4079], 'predictions,': [756], 'usually': [757], 'profiling': [762, 1302], '(5Huang': [763], 'F.': [764, 776, 939, 1885, 2556, 2720, 2839, 4270], 'Reeves': [765], 'K.': [766, 1281, 1869, 1905, 2540, 2576, 2704, 2740, 2823, 2859, 4117, 4171], 'Han': [767], 'X.': [768], 'Fairchild': [769], 'C.': [770, 943, 997, 1283, 1334, 1344, 1891, 2562, 2726, 2845, 3781, 4123, 4131], 'Platero': [771], 'Wong': [773, 1948, 2619, 2783, 2902], 'T.W.': [774], 'Lee': [775, 4188], 'Shaw': [777], 'P.': [778, 945, 1057, 1695, 1875, 2546, 2710, 2829, 4193, 4201, 4217, 4219, 4278], 'Clark': [779, 4106], 'E.': [780, 1118, 1234, 4185, 4187], 'Identification': [781], 'sensitivity': [787], 'tumors': [790], 'dasatinib:': [792], 'Rationale': [793], 'selection.Cancer': [796], 'Res.': [797, 4235, 4257], '67:': [799], '2226-2238Crossref': [800], '(280)': [803], '6Dressman': [806], 'H.K.': [807], 'Berchuck': [808], 'A.': [809, 815, 833, 1230, 1340, 1665, 1667, 2113, 4109, 4165], 'Chan': [810], 'Zhai': [812], 'Bild': [814], 'Sayer': [816], 'R.': [817, 1232, 1881, 1899, 1917, 2552, 2570, 2588, 2716, 2734, 2752, 2835, 2853, 2871, 4081, 4115, 4145, 4181, 4191, 4197, 4223], 'Cragun': [818], 'Clarke': [820], 'Whitaker': [822], 'R.S.': [823, 4163], 'Gray': [826], 'Marks': [828], 'Ginsburg': [830], 'G.S.': [831], 'Potti': [832], 'West': [834], 'M.': [835, 947, 974, 1285, 1316, 1324, 1332, 1675, 1877, 1883, 1911, 1923, 1929, 1947, 2115, 2548, 2554, 2582, 2594, 2600, 2618, 2712, 2718, 2746, 2758, 2764, 2782, 2831, 2837, 2865, 2877, 2883, 2901, 3596, 3789, 4113, 4133, 4143, 4203, 4209, 4246], 'Nevins': [836], 'J.R.': [837], 'Lancaster': [838], 'An': [840], 'integrated': [841], 'genomic-based': [842], 'approach': [843, 2131, 4077], 'individualized': [845, 3603], 'treatment': [846, 1793, 2341], 'advanced-stage': [850], 'ovarian': [851], '25:': [856, 1371], '517-525Crossref': [857], '(222)': [860], 'To': [863, 3460, 3535, 4089, 4379], 'knowledge,': [865], 'no': [866, 1770, 3948], 'successfully': [868], 'global': [873, 911], 'profiles': [875, 1602], 'so': [876], 'far.': [877], 'spectrometry,': [882], 'methods': [883, 916], 'enriching': [885], 'phosphorylated': [886, 1754, 3159], 'peptides,': [889, 3162], 'computer': [891], 'algorithms': [892], 'analyzing': [894], 'proteomics': [895, 904, 1359, 3795], 'enabled': [898], 'application': [900], 'spectrometry-based': [903], 'monitor': [906], 'events': [908, 1013], 'unbiased': [913, 1767], 'manner.': [914], 'These': [915, 1991], 'become': [918], 'sufficiently': [919, 3922], 'robust': [922], 'localize': [924], 'quantify': [926], 'within': [930, 2371], 'peptide': [932, 3120, 3165, 3600, 3626, 3650, 3706], 'sequence': [933], '(7Olsen': [934], 'J.V.': [935, 976, 1293], 'Blagoev': [936, 2104], 'B.': [937, 941, 972, 1072, 1354, 1673, 1677, 1689, 2105, 4121, 4173], 'Gnad': [938], 'Macek': [940], 'Kumar': [942], 'Mortensen': [944], 'Mann': [946, 973, 2114, 3595, 3788], 'Global,': [948], 'vivo,': [950], 'site-specific': [952, 979], 'dynamics': [954], 'signaling': [956, 1775], 'networks.Cell.': [957], '2006;': [958], '127:': [959], '635-648Abstract': [960], 'Full': [961, 963, 1134, 1136, 2140, 2142, 3474, 3805, 3807], 'Text': [962, 964, 1135, 1137, 2141, 2143, 3806, 3808], 'PDF': [965, 1138, 2144, 3809], '(2807)': [968], '8Macek': [971], 'Olsen': [975, 1292], 'Global': [977], 'phosphoproteomics:': [981], 'Principles': [982], 'applications.Annu.': [984], 'Pharmacol.': [986], 'Toxicol.': [987], '49:': [989], '199-221Crossref': [990], '(345)': [993], '9Schaab': [996], 'Analysis': [998, 3790], 'phosphoproteomics': [1000, 1596], 'data.Methods': [1001], 'Mol.': [1002], 'Biol.': [1003], '2011;': [1004], '696:': [1005], '41-57Crossref': [1006], '(13)': [1009], 'Phosphorylation': [1012], 'important': [1015, 1042], 'signal': [1017, 1037], 'transduction,': [1018], 'signals': [1020], 'caused': [1021], 'by': [1022, 1184, 1215, 1499, 1534, 1752, 1810, 1825, 2119, 2170, 2331, 2405, 2484, 2495, 2977, 3016, 3024, 3095, 3109, 3124, 3212, 3269, 3283, 3343, 3352, 3392, 3740, 4047, 4059], 'external': [1023], 'stimuli': [1024], 'transmitted': [1026], 'membrane': [1030], 'nucleus.': [1033], 'Aberrations': [1034], 'transduction': [1038], 'particularly': [1041], 'understanding': [1044], 'mechanisms': [1046, 1084, 1361], 'certain': [1048, 4101], 'diseases,': [1049], 'such': [1050], 'cancer,': [1052], 'inflammation,': [1053], 'diabetes': [1055], '(10Blume-Jensen': [1056], 'Hunter': [1058], 'T.': [1059, 1240, 1328, 1342, 1669, 1871, 1887, 1907, 2542, 2558, 2578, 2706, 2722, 2742, 2825, 2841, 2861, 3783, 4175, 4221], 'Oncogenic': [1060], 'signalling.Nature.': [1062], '2001;': [1063], '411:': [1064], '355-365Crossref': [1065], '(3132)': [1068], '11Kaminska': [1071], 'MAPK': [1073, 1750], 'signalling': [1074], 'targets': [1078], 'anti-inflammatory': [1080], 'therapy:': [1081], 'benefits.Biochim.': [1087], 'Biophys.': [1088], 'Acta.': [1089], '2005;': [1090], '1754:': [1091], '253-262Crossref': [1092], '(994)': [1095], 'Approximately': [1098, 1154], '391,000': [1099], 'incidences': [1100, 1160], '342,000': [1102], 'deaths': [1103, 1151], 'were': [1107, 1579, 1590, 1603, 1985, 1995, 2032, 2046, 2070, 2152, 2168, 2196, 2206, 2233, 2279, 2301, 2320, 2354, 2432, 2473, 2482, 2529, 2693, 2697, 2816, 2937, 2954, 2971, 3048, 3122, 3145, 3210, 3245, 3273, 3293, 3303, 3308, 3319, 3331, 3390, 3476, 3509, 3527, 3565, 3571, 3585, 3670, 3695, 3716, 3774, 3823, 3877, 3918, 3937, 3950, 4022, 4053, 4338], 'estimated': [1108], 'Europe': [1110, 1126], '2008': [1112], '(12Ferlay': [1113], 'Parkin': [1115], 'D.M.': [1116], 'Steliarova-Foucher': [1117], 'Estimates': [1119], 'incidence': [1122], 'mortality': [1124], '2008.Eur.': [1128], 'Cancer.': [1130], '2010;': [1131, 1473, 1713], '46:': [1132], '765-781Abstract': [1133], '(1887)': [1141], 'Scholar),': [1143, 1973, 4265], 'accounting': [1144], 'nearly': [1146], '20%': [1147], 'all': [1149, 1157], 'Europe.': [1153], '85%': [1155], '(NSCLC)': [1166], '1The': [1167, 1198], 'abbreviations': [1168, 1199], 'are:AUROCarea': [1170, 1201], 'under': [1171, 1202, 1482, 1517, 3152], 'receiver': [1173, 1204, 1484, 1519], 'operating': [1174, 1205, 1485, 1520], 'characteristic': [1175, 1206, 1486, 1521], 'curveCVcross-validationFDRfalse': [1176, 1207], 'discovery': [1177, 1208, 1490, 1525, 3744, 4071], 'rateNSCLCnon-small': [1178, 1209], 'cancerSILACstable': [1181, 1212], 'isotope': [1182, 1213, 1497, 1532, 2093, 2117], 'labeling': [1183, 1214, 1498, 1533, 2084, 2094, 2118], 'amino': [1185, 1216, 1500, 1535, 2096, 2120, 2194, 2223, 3656], 'acid': [1186, 1217, 1501, 1536], 'cultureSVMsupport': [1189, 1220], 'vector': [1190, 1221, 1506, 1541], 'machineGOgene': [1191, 1222], 'ontologyKEGGkyoto': [1192, 1223], 'encyclopedia': [1193, 1224, 1511, 1546], 'genes': [1195, 1226, 1513, 1548, 4284], 'genomes.': [1197, 1228, 1515, 1550], '(13Jemal': [1229], 'Siegel': [1231], 'Ward': [1233], 'Hao': [1235], 'Y.': [1236, 1320, 4065, 4067], 'Xu': [1237], 'Murray': [1239], 'Thun': [1241], 'M.J.': [1242], 'Cancer': [1243, 1246], 'statistics,': [1244], '2008.CA': [1245], '2008;': [1249, 3612], '58:': [1250], '71-96Crossref': [1251], '(10196)': [1254], 'Dasatinib': [1257, 1402], '(Sprycel®;': [1258], 'Bristol-Myers': [1259], 'Squibb)': [1260], 'multikinase': [1263], 'targeting': [1265], 'BCR-ABL,': [1266], 'Src': [1268, 1420], 'family,': [1270], 'c-Kit,': [1271], 'ephrin': [1272], 'receptors,': [1273], 'platelet-derived': [1275], 'factor': [1277], 'receptor': [1278], 'β': [1279], '(14Sharma': [1280], 'Weber': [1282], 'Bairlein': [1284], 'Greff': [1286], 'Kéri': [1288], 'Cox': [1290, 3786], 'Daub': [1294], 'H.': [1295, 1935, 2111, 2606, 2770, 2889, 4066, 4135, 4274], 'Proteomics': [1296], 'strategy': [1297], 'interaction': [1301, 4422], 'extracts.Nat.': [1305], 'Methods.': [1306], '741-744Crossref': [1309], '(116)': [1312], '15Bantscheff': [1315], 'Eberhard': [1317], 'Abraham': [1319], 'Bastuck': [1321], 'Boesche': [1323], 'Hobson': [1325], 'Mathieson': [1327], 'Perrin': [1329], 'Raida': [1331], 'Rau': [1333], 'Reader': [1335], 'Sweetman': [1337], 'Bauer': [1339], 'Bouwmeester': [1341], 'Hopf': [1343], 'Kruse': [1345], 'U.': [1346], 'Neubauer': [1347], 'Ramsden': [1349], 'N.': [1350, 1452, 4215], 'Rick': [1351], 'Kuster': [1353], 'Drewes': [1355], 'Quantitative': [1357], 'chemical': [1358], 'reveals': [1360], 'action': [1363], 'clinical': [1365, 1405], 'ABL': [1366], 'inhibitors.Nat.': [1368], 'Biotechnol.': [1369, 3611], '1035-1044Crossref': [1372], '(860)': [1375], 'It': [1378], 'approved': [1381], 'chronic': [1383], 'myelogenous': [1384], 'leukemia': [1385], 'Philadelphia': [1387], 'chromosome-positive': [1388], 'acute': [1389], 'lymphoblastic': [1390], 'leukemia.': [1391], 'clinically': [1395], 'evaluated': [1396, 1615], 'advanced': [1400, 1467], 'NSCLC.': [1401], 'had': [1403, 4038], 'modest': [1404], 'activity,': [1406], 'partial': [1410], 'stable': [1414, 1496, 1531, 2092], 'diseases': [1415], 'among': [1416], '30': [1417, 2379, 2451, 2464, 3064, 3074], 'patients.': [1418], 'Neither': [1419], 'family': [1421], 'activation': [1423, 3543], 'nor': [1424], 'EGFR': [1425], 'K-ras': [1427], 'mutations': [1428], 'could': [1429], '(16Johnson': [1435], 'F.M.': [1436], 'Bekele': [1437], 'B.N.': [1438], 'Feng': [1439], 'Wistuba': [1441], 'I.': [1442, 1687, 1895, 2107, 2566, 2730, 2849], 'Tang': [1443], 'X.M.': [1444], 'Tran': [1445], 'H.T.': [1446], 'Erasmus': [1447], 'J.J.': [1448], 'Hwang': [1449], 'L.L.': [1450], 'Takebe': [1451], 'Blumenschein': [1453], 'G.R.': [1454], 'Lippman': [1455], 'S.M.': [1456], 'Stewart': [1457], 'Phase': [1459], 'II': [1460], 'non-small-cell': [1468], '28:': [1474, 4259], '4609-4615Crossref': [1475], '(138)': [1478], 'area': [1481, 1516, 4362], 'curve': [1487, 1522, 2510], 'false': [1489, 1524, 3743, 4070], 'rate': [1491, 1526, 3236, 3745], 'culture': [1504, 1539, 2100, 3034], 'support': [1505, 1540], 'machine': [1507, 1542], 'ontology': [1509, 1544], 'kyoto': [1510, 1545], 'In': [1551, 1573, 1652, 1762, 2310, 4305, 4414], 'this': [1552, 1619, 2812, 2931, 3835, 3880, 4006, 4333, 4364], 'wanted': [1555], 'NSCLC': [1570, 1576, 1854, 2230], 'total,': [1574, 2311], '26': [1575, 1992, 2525], 'lines': [1578, 1589, 1856, 1976, 1994, 2031, 2045, 2088, 2232, 2278, 2326, 2528, 2668, 2692, 2936, 2953], 'their': [1582, 4342], 'dasatinib.': [1585], 'identical': [1587], 'unbiased,': [1595], 'study,': [1597, 1655, 2813], 'obtained': [1600, 1996, 2033], 'assemble': [1606], 'biomarker': [1608], 'sites.': [1613], 'performance': [1617], 'setup': [1624], 'investigated': [1626, 1785], 'robustness': [1628], 'features.': [1633], 'Finally,': [1634], 'confirmed': [1636, 1801], 'power': [1639], 'independent': [1645], 'set': [1646, 3653, 3729, 4349], 'recent': [1654], 'Andersen': [1656], 'et': [1657, 1864], 'al.': [1658, 1865], '(17Andersen': [1659], 'J.N.': [1660], 'Sathyanarayanan': [1661], 'Di': [1663], 'Bacco': [1664], 'Chi': [1666], 'Zhang': [1668], 'Chen': [1670, 1932, 2603, 2767, 2886], 'A.H.': [1671], 'Dolinski': [1672, 4170], 'Kraus': [1674], 'Roberts': [1676], 'Arthur': [1678], 'W.': [1679, 1901, 1903, 2572, 2574, 2736, 2738, 2855, 2857, 4195], 'Klinghoffer': [1680], 'R.A.': [1681], 'Gargano': [1682], 'Feldman': [1686], 'Lynch': [1688], 'Rush': [1690], 'Hendrickson': [1692], 'R.C.': [1693], 'Blume-Jensen': [1694], 'Paweletz': [1696], 'C.P.': [1697], 'Pathway-based': [1698], 'identification': [1699, 3601, 3892, 3956], 'therapeutics:': [1704], 'Personalized': [1705], 'oncology': [1706], 'PI3K': [1708], 'pathway': [1709], 'inhibitors.Sci.': [1710], 'Transl.': [1711], 'Med.': [1712], '43ra55Crossref': [1715], '(141)': [1718], 'Scholar)': [1720, 3619, 3813, 4241, 4302], 'phosphatidylinositol': [1727, 1747], '3-kinase': [1728, 1748], 'inhibitors.': [1729], 'Their': [1730], 'differs': [1732], 'two': [1734, 2430, 2650, 2815, 3884], 'aspects': [1735], 'presented': [1739], 'here.': [1740], 'First,': [1741, 2400], 'authors': [1743, 1783], 'focused': [1744], 'immunoprecipitating': [1753], 'peptides': [1755, 3144, 3209, 3272, 3292, 3302, 3307, 3389, 3754], 'antibodies': [1757], 'directed': [1758], 'phosphomotifs.': [1761], 'contrast,': [1763], 'followed': [1765, 3094], 'approach,': [1768], 'hypothesis': [1771], 'about': [1772, 3844], 'made.': [1780], 'Second,': [1781], 'first': [1784, 3156], 'regulation': [1787, 3851], 'upon': [1791], 'line': [1798, 2300, 3043, 3866], 'subsequently': [1800, 3057, 3136], 'applicability': [1803], 'site': [1806], 'prediction': [1809], 'evaluating': [1811], 'its': [1812, 3845], 'started': [1823], 'directly': [1824, 2973, 3351, 3414], 'investigating': [1826], 'Based': [1839], 'half-maximum': [1842], 'inhibitory': [1844], 'concentrations': [1845, 2441], '(GI50)': [1846], '84': [1853], 'reported': [1857, 2534, 4046], 'supplemental': [1859, 1988, 2038, 3053, 3979], 'Table': [1860, 1989, 2039], '5': [1861, 2992, 2995, 3917], 'Sos': [1863], '(18Sos': [1866], 'M.L.': [1867, 2538, 2702, 2821], 'Michel': [1868, 2539, 2703, 2822], 'Zander': [1870, 2541, 2705, 2824], 'Weiss': [1872, 2543, 2707, 2826], 'Frommolt': [1874, 2545, 2709, 2828], 'Peifer': [1876, 2547, 2711, 2830], 'Ullrich': [1880, 2551, 2715, 2834], 'Koker': [1882, 2553, 2717, 2836], 'Fischer': [1884, 1892, 2555, 2563, 2719, 2727, 2838, 2846, 3425], 'Shimamura': [1886, 2557, 2721, 2840], 'Rauh': [1888, 2559, 2723, 2842], 'Mermel': [1890, 2561, 2725, 2844], 'Stückrath': [1894, 2565, 2729, 2848], 'Heynck': [1896, 2567, 2731, 2850], 'Beroukhim': [1898, 2569, 2733, 2852], 'Lin': [1900, 2571, 2735, 2854], 'Winckler': [1902, 2573, 2737, 2856], 'Shah': [1904, 2575, 2739, 2858], 'LaFramboise': [1906, 2577, 2741, 2860], 'Moriarty': [1908, 2579, 2743, 2862], 'W.F.': [1909, 2580, 2744, 2863], 'Hanna': [1910, 2581, 2745, 2864], 'Tolosi': [1912, 2583, 2747, 2866], 'Rahnenführer': [1914, 2585, 2749, 2868], 'Verhaak': [1916, 2587, 2751, 2870], 'Chiang': [1918, 2589, 2753, 2872], 'Getz': [1920, 2591, 2755, 2874], 'Hellmich': [1922, 2593, 2757, 2876], 'Wolf': [1924, 2595, 2759, 2878], 'Girard': [1926, 2597, 2761, 2880], 'Peyton': [1928, 2599, 2763, 2882], 'Weir': [1930, 2601, 2765, 2884], 'B.A.': [1931, 2602, 2766, 2885], 'T.H.': [1933, 2604, 2768, 2887], 'Greulich': [1934, 2605, 2769, 2888], 'Barretina': [1936, 2607, 2771, 2890], 'Shapiro': [1938, 2609, 2773, 2892], 'G.I.': [1939, 2610, 2774, 2893], 'Garraway': [1940, 2611, 2775, 2894], 'L.A.': [1941, 2612, 2776, 2895], 'Gazdar': [1942, 2613, 2777, 2896], 'A.F.': [1943, 2614, 2778, 2897], 'Minna': [1944, 2615, 2779, 2898], 'J.D.': [1945, 2616, 2780, 2899], 'Meyerson': [1946, 2617, 2781, 2900], 'K.K.': [1949, 2620, 2784, 2903], 'Thomas': [1950, 2621, 2785, 2904], 'R.K.': [1951, 2622, 2786, 2905], 'Predicting': [1952, 2623, 2787, 2906], 'susceptibility': [1954, 2625, 2789, 2908], 'cancers': [1959, 2630, 2794, 2913], 'genetic': [1962, 2633, 2797, 2916, 4435], 'lesions.J.': [1963, 2634, 2798, 2917], 'Invest.': [1965, 2636, 2800, 2919], '119:': [1967, 2638, 2802, 2921], '1727-1740Crossref': [1968, 2639, 2803, 2922], '(223)': [1971, 2642, 2806, 2925], '13': [1974, 1980], 'low': [1978, 4359], 'high': [1982, 3599, 3792], 'GI50': [1983, 2398, 2517, 2521, 2663, 2685], 'values': [1984, 2522, 2533, 4011, 4045], '(cf.': [1987], 'S1).': [1990, 2040], 'LGC': [1998, 2035, 2252], 'Standards': [1999, 2036], '(Wesel,': [2000], 'Germany),': [2001, 2011], 'Deutsche': [2004, 2259], 'Sammlung': [2005, 2260], 'von': [2006, 2261], 'Mikroorganismen': [2007, 2262], 'und': [2008, 2263], 'Zellkulturen': [2009], '(Braunschweig,': [2010], 'Roman': [2013], "Thomas's": [2014], 'group': [2015, 4021], 'at': [2016, 2226, 2307, 2944, 3076, 3234, 3381, 3406, 3427, 3481, 3517, 4013, 4025], 'Max': [2018], 'Planck': [2019], 'Institute': [2020], 'Neurological': [2022, 2273], 'Research': [2023], '(Cologne,': [2024], 'Germany).': [2025, 2067, 2082, 2351], '(see': [2037], 'All': [2041, 3940], 'cultivated': [2047, 2153, 2207, 2355], 'RPMI': [2049], '1640,': [2050], '10%': [2051], 'fetal': [2052, 2161], 'bovine': [2053, 2162], 'serum,': [2054], '2': [2055, 3396, 3432], 'mm': [2056, 2059, 2988, 2993, 2996, 3062, 3071, 3101, 3180, 3229, 3314], 'glutamine,': [2057], '1': [2058, 2457, 2688, 3170, 3276], 'sodium': [2060], 'pyruvate,': [2061], 'penicillin/streptomycin': [2063], '(PAA': [2064], 'Laboratories,': [2065, 2368], 'Cölbe,': [2066], 'cells': [2069, 2151, 2205, 2296, 2353, 2682, 2970], 'routinely': [2071], 'monitored': [2072], 'mycoplasma': [2074], 'infection': [2075], 'MycoAlert': [2078], 'reagents': [2079], '(Lonza,': [2080], 'Cologne,': [2081], 'Metabolic': [2083], 'performed': [2090, 2506, 4370], 'acids': [2097, 2121, 2195, 2224], '(SILAC)': [2101], '(19Ong': [2102], 'S.E.': [2103], 'Kratchmarova': [2106], 'Kristensen': [2108], 'D.B.': [2109], 'Steen': [2110], 'Pandey': [2112], 'Stable': [2116], 'culture,': [2124], 'SILAC,': [2125], 'simple': [2128], 'accurate': [2130], 'proteomics.Mol.': [2134], 'Cell.': [2135, 3801], 'Proteomics.': [2136, 3802], '2002;': [2137], '1:': [2138], '376-386Abstract': [2139], '(4569)': [2147], 'media': [2155], 'containing': [2156], 'SILAC-RPMI': [2157], '(PAA)': [2158], 'dialyzed': [2160], 'serum': [2163], '(Invitrogen).': [2164], 'l-Lysine': [2165], 'l-arginine': [2167, 2175], 'replaced': [2169], 'normal': [2171], 'l-lysine': [2172], '(Lys0)': [2173], '(Arg0),': [2176], 'medium': [2178, 2283, 2957, 3038], 'isotope-labeled': [2179, 2187], 'l-D414N2-lysine': [2180], '(Lys4)': [2181], 'l-13C614N4-arginine': [2183], '(Arg6),': [2184], 'heavy': [2186, 2959, 3040], 'l-13C615N2-lysine': [2188], '(Lys8)': [2189], 'l-13C615N4-arginine': [2191], '(Arg10).': [2192], 'Isotope-labeled': [2193], 'purchased': [2197], 'Cambridge': [2199], 'Isotope': [2200], 'Laboratories': [2201], '(Andover,': [2202], 'MA).': [2203], 'minimum': [2210], 'doubling': [2213], 'times': [2214], 'obtain': [2216], 'incorporation': [2218], 'efficiency': [2219], 'labeled': [2222, 2295, 3041], 'least': [2227, 4014, 4026], '95%.': [2228], '16': [2229], 'reference': [2237, 3032], 'pool:': [2238], 'A549,': [2239], 'Calu6,': [2240], 'H1395,': [2241], 'H1437,': [2242], 'H1755,': [2243], 'H2030,': [2244], 'H2052,': [2245], 'H2172,': [2246], 'H28,': [2247], 'H460,': [2248], 'HCC827': [2249], '(obtained': [2250, 2256, 2269], 'Standards),': [2253], 'LCLC103H,': [2254], 'LouNH91': [2255], 'Zellkulturen),': [2264], 'H322M,': [2265], 'HCC2279,': [2266], 'HCC2429': [2268], 'MPI': [2271], 'Research).': [2274], 'grown': [2280, 2955], 'SILAC': [2282, 2960, 3705], 'supplemented': [2284, 3226], 'natural': [2287], '"light"': [2288], 'forms': [2289, 3711], 'arginine': [2291, 3715], 'lysine.': [2293], 'each': [2298, 2319, 2426, 2442, 2486, 3766, 3864, 4020], 'lysed,': [2302], 'pooled,': [2303], 'aliquoted,': [2304], 'stored': [2306], '−80': [2308], '°C.': [2309], '40': [2312, 3232], 'aliquots': [2313], 'mg': [2316, 3045], 'generated.': [2321], 'Sensitivity': [2322], 'determined': [2330, 2404, 3023], 'measuring': [2332], 'ATP': [2335], 'content': [2336], '96': [2338], 'h': [2339, 3093], 'CellTiter': [2344], 'Glo': [2345], 'chemiluminescent': [2346], 'viability': [2347], 'assay': [2348], '(Promega,': [2349], 'Mannheim,': [2350], '96-well': [2357, 2436], 'plates': [2358, 2976], '(Greiner,': [2359], 'Frickenhausen,': [2360], 'Germany)': [2361, 2392], 'presence': [2364], '(LC': [2367], 'Woburn,': [2369], 'MA)': [2370], 'concentration': [2373, 2470, 2492, 3021, 3132], 'range': [2374], '3': [2376, 2447, 2459, 3238, 3376], 'nm': [2377, 2444], 'μm.': [2380], 'raw': [2382, 3581], 'chemiluminometer': [2386], '(FLUOstar': [2387], 'OPTIMA;': [2388], 'BMG': [2389], 'Labtech,': [2390], 'Offenburg,': [2391], 'determine': [2396], 'value.': [2399, 2518], 'background': [2402], 'calculating': [2406], 'median': [2408, 2497], 'value': [2409, 2421, 2686, 3496, 3520, 4361], "plate's": [2412], 'border': [2413], 'wells,': [2414], 'contained': [2416], 'media.': [2419], 'This': [2420], 'then': [2423], 'subtracted': [2424], 'inner': [2427], 'well.': [2428], 'conducted': [2433], 'plate': [2437], '10': [2439, 2449, 2461], 'compound': [2440], '(0': [2443], '(DMSO': [2445], 'control),': [2446], 'nm,': [2448, 2450, 2452, 2454, 2456], '100': [2453], '300': [2455], 'μm,': [2458, 2460, 2462, 2689], 'μm),': [2465], 'three': [2466, 3666], 'points': [2468, 4037], 'per': [2469], 'experiment': [2472], 'available.': [2474], 'Ratios': [2475], 'representing': [2476], 'percentage': [2478], 'inhibition': [2481], 'calculated': [2483, 2520], 'dividing': [2485], 'point': [2488], 'coming': [2489], '>0': [2493], 'nM': [2494], 'DMSO': [2500], 'values.': [2501], 'logistic': [2503], 'regression': [2504], 'fit': [2508], 'those': [2512], 'ratios': [2513], 'compute': [2515], 'compared': [2530], 'Ref.': [2536, 2700, 2819], '18Sos': [2537, 2701, 2820], 'Scholar.': [2644], 'Although': [2645], 'correlation': [2647, 2655], 'sets': [2651], 'strong': [2653, 3173, 3218, 3262], '(Pearson': [2654], '=': [2656, 2659, 3485], '0.50,': [2657], 'p': [2658, 4044], '0.009': [2660], 'logged': [2662], 'values),': [2664], 'few': [2666], 'inconsistent': [2670], 'behavior.': [2671], 'By': [2672], 'setting': [2673], 'threshold': [2675], 'discriminate': [2677], 'seven': [2690], 'classified': [2694], 'inconsistently': [2695], '(five': [2696], 'Scholar': [2808, 2927], 'but': [2809, 2928], 'study).': [2932], 'Consequently,': [2933], 'excluded': [2938, 3573], 'workflow': [2941], 'aims': [2943], 'finding': [2945], 'phosphosignature.': [2948, 3831], 'Responsive': [2949], 'nonresponsive': [2951], 'medium,': [2961], 'washing': [2964], 'twice': [2965], 'ice-cold': [2967, 2981], 'PBS,': [2968], 'lysed': [2972], 'addition': [2979, 3111, 3126], 'lysis': [2982], 'buffer': [2983, 3177, 3222], '(8': [2984], 'm': [2985], 'urea,': [2986], '50': [2987, 3100], 'Tris,': [2989, 3102], 'pH': [2990, 3103, 3182], '8.2,': [2991], 'EDTA,': [2994], 'EGTA,': [2997], 'Sigma': [2998], 'HALT': [2999], 'phosphatase': [3000], 'mix,': [3002], 'Roche': [3003], 'Applied': [3004], 'Science': [3005], 'complete': [3006, 3537], 'protease': [3007], 'mix).': [3009], 'After': [3010, 3982], 'sonication': [3011], 'debris': [3013], 'sedimented': [3015], 'centrifugation,': [3017], 'Bradford': [3025], 'assays.': [3026], 'Equal': [3027], 'amounts': [3029], 'mix': [3035], '(7': [3044], 'each)': [3047, 3244], 'mixed': [3049], 'depicted': [3051], 'Fig.': [3054], 'S2': [3055], 'subjected': [3058, 3332, 3951], 'reduction': [3060], '(20': [3061], 'DTT,': [3063], 'min': [3065, 3075, 3233], '37': [3066], '°C)': [3067], 'alkylation': [3069], '(50': [3070], 'iodoacetamide': [3072], 'room': [3077], 'temperature)': [3078], 'prior': [3079], 'proteolytic': [3081, 3662], 'cleavage.': [3082], 'Then': [3083], '80': [3084], 'μg': [3085, 3114], 'LysC': [3087], '(Wako)': [3088], 'added': [3090], '4': [3092], '4-fold': [3097], 'dilution': [3098], '8.2.': [3104], 'Proteolytic': [3105], 'cleavage': [3106, 3668], 'continued': [3108], '120': [3113], 'trypsin': [3116, 3658], '(Promega)': [3117], 'overnight.': [3118], 'mixtures': [3121], 'acidified': [3123], 'TFA': [3128, 3280], 'final': [3131], '0.5%': [3134, 3298, 3404], 'desalted': [3137, 3282], 'via': [3138, 4371, 4424], 'C18': [3139, 3285], 'SephPack': [3140], 'columns': [3141], '(Waters).': [3142, 3289], 'eluted': [3146, 3294, 3391], '50%': [3148, 3296], 'ACN': [3149], 'dried': [3151, 3164], 'vacuum.': [3153], 'For': [3154, 4005, 4332], 'separation': [3157], 'nonphosphorylated': [3161], 'powder': [3166], 'reconstituted': [3168, 3274, 3309], 'ml': [3171, 3243, 3277], 'cation': [3174, 3219, 3263], 'exchange': [3175, 3220, 3264], 'chromatography': [3176, 3201, 3221, 3256, 3265], '(5': [3179], 'K2HPO4,': [3181], '2.7,': [3183], '30%': [3184], 'ACN)': [3185], 'loaded': [3187, 3350], 'onto': [3188], 'polysulfoethyl': [3190], 'column': [3191], '(9.4': [3192], '×': [3193], '250': [3194], 'mm;': [3195], 'PolyLC)': [3196], 'ÄKTA': [3199], 'purifier': [3200], 'system': [3202, 3357], 'equipped': [3203], 'fraction': [3206], 'collector.': [3207], 'separated': [3211], 'linear': [3214, 3532], 'gradient': [3215, 3394], '25%': [3217], 'B': [3223, 3401, 4085], '(buffer': [3224], '500': [3228, 3385], 'KCl)': [3230], 'over': [3231], 'flow': [3235, 3383, 3408], 'ml/min.': [3239], 'Twenty': [3240], 'fractions': [3241, 3266], '(12': [3242], 'collected': [3246], 'across': [3247], 'gradient.': [3249], 'Prior': [3250], 'immobilized': [3252], 'metal': [3253], 'ion': [3254, 3437, 3448, 3533], 'affinity': [3255], 'enrichment,': [3257], 'solvent': [3259, 3400], 'removed': [3268], 'lyophilization.': [3270], 'Dried': [3271, 3306], '0.1%': [3279], 'reversed': [3286, 3371], 'phase': [3287, 3372], 'cartridges': [3288], 'bound': [3291, 3388], 'ACN,': [3297, 3312, 3403], 'HOAc,': [3299], 'lyophilized': [3304], 'again.': [3305], '40%': [3311, 3398], '25': [3313], 'formic': [3315], 'acid,': [3316], 'phosphopeptides': [3318, 3330], 'captured': [3320], 'PhosSelect': [3322], '(Sigma)': [3323], 'according': [3324, 4340], "manufacturer's": [3327], 'instructions.': [3328], 'Eluted': [3329], 'spectrometric': [3335, 3338], 'analysis.': [3336, 3816, 3954], 'Mass': [3337], 'analysis': [3339, 4007, 4268, 4368], 'carried': [3341], 'out': [3342], 'on-line': [3344], 'nano': [3345], 'LC-MS/MS.': [3346], 'sample': [3348], 'Agilent': [3354], '1200': [3355], 'nanoflow': [3356], '(Agilent': [3358], 'Technologies)': [3359], '15-cm': [3362], 'fused': [3363], 'silica': [3364], 'emitter': [3365], '(New': [3366], 'Objective)': [3367], 'packed': [3368], 'in-house': [3369], 'material': [3373], '(Reprusil-Pur': [3374], 'C18-AQ,': [3375], 'μm;': [3377], 'Dr.': [3378], 'Maisch': [3379], 'GmbH)': [3380], 'nl/min.': [3386], '(80%': [3402], 'HOAc)': [3405], '200': [3410], 'nl/min': [3411], 'sprayed': [3413], 'into': [3415], 'LTQ-Orbitrap': [3417, 3420], 'XL': [3418], 'Discovery': [3421], 'spectrometer': [3423, 3442], '(Thermo': [3424], 'Scientific)': [3426], 'spray': [3429], 'voltage': [3430], 'kV': [3433], 'applying': [3434, 3547, 3620, 4060], 'nanoelectrospray': [3436], 'source': [3438, 3826], '(ProxeonBiosystems).': [3439], 'operated': [3444], 'positive': [3447], 'mode': [3449], 'data-dependent': [3453, 3569], 'MS': [3456, 3466, 3508], 'MS/MS': [3458, 3767], 'acquisition.': [3459], 'improve': [3461, 3536], 'accuracy': [3463], 'mode,': [3467], 'lock': [3469], 'option': [3471, 3544], 'enabled.': [3473], 'scans': [3475], 'acquired': [3477], 'orbitrap': [3480], 'resolution': [3483], 'r': [3484], '60,000': [3486], '(Orbitrap': [3487, 3491], 'XL)': [3488], '30,000': [3490], 'Discovery)': [3492], '1,000,000': [3498], 'ions.': [3499], 'five': [3501], 'intense': [3503], 'ions': [3504], 'detected': [3505], 'collision-induced': [3512], 'dissociation': [3513, 3538, 3549], 'LTQ': [3516], '5000.': [3522], 'resulting': [3524], 'fragmentation': [3525], 'spectra': [3526, 3970], 'also': [3528, 3938], 'recorded': [3529], 'trap.': [3534], 'phosphopeptides,': [3540], 'multistage': [3542], 'enabled,': [3546], 'additional': [3548], 'energy': [3550], 'potential': [3552], 'neutral': [3553], 'loss': [3554], 'fragments': [3555], '(precursor': [3556], 'minus': [3557], '98,': [3558], '49,': [3559], '32.7': [3561], 'Thompson).': [3562], 'Ions': [3563], 'once': [3566], 'acquisition': [3570], 'dynamically': [3572], '90': [3575], 's': [3576], 'fragmentation.': [3579], 'spectral': [3583], 'processed': [3586], 'MaxQuant': [3589, 3597, 3701, 3772, 3820, 3871], 'software': [3590], '(version': [3591], '1.1.1.25)': [3592], '(20Cox': [3593], 'enables': [3598], 'rates,': [3602], 'p.p.b.-range': [3604], 'accuracies': [3606], 'proteome-wide': [3608], 'quantification.Nat.': [3610], '26:': [3613], '1367-1372Crossref': [3614], '(9150)': [3617], 'Andromeda': [3622], 'search': [3623, 4352], 'engine': [3624], 'identification.': [3629], 'human': [3631], 'UNIPROT': [3632, 3644], 'database': [3633, 3640, 3779, 4230], '(version:': [3634], '57.12)': [3635], '110,595': [3639], 'entries': [3641], 'including': [3642], 'splice': [3645], 'variants': [3646], 'database.': [3647], 'minimal': [3649], 'length': [3651], '6': [3655, 4032], 'acids,': [3657], 'enzyme,': [3663], 'maximally': [3665], 'missed': [3667], 'allowed.': [3671], 'Carbamidomethylation': [3672], 'cysteines': [3674], 'fixed': [3679], 'modification,': [3680], 'whereas': [3681], 'methionine': [3682], 'oxidation,': [3683], 'N-terminal': [3684], 'acetylation,': [3686], 'serine,': [3690], 'threonine,': [3691], 'tyrosine': [3693], 'residues': [3694], 'considered': [3696, 3919, 4023], 'variable': [3698], 'modifications.': [3699], 'automatically': [3702, 3717], 'extracts': [3703], 'isotopic': [3704, 3710], 'triplets,': [3707], 'lysine': [3713], 'selected.': [3718], 'maximal': [3720], 'deviation': [3722], 'precursor': [3724], 'fragment': [3726, 3969], 'masses': [3727], '20': [3731], 'ppm': [3732], '0.5': [3734], 'Da': [3735], 'before': [3736], 'internal': [3737], 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