J Chem Inf Model - Discovering new agents active against methicillin-resistant Staphylococcus aureus with ligand-based approaches.

Tópicos

{ compound(1573) activ(1297) structur(1058) }
{ model(2656) set(1616) predict(1553) }
{ featur(3375) classif(2383) classifi(1994) }
{ data(3008) multipl(1320) sourc(1022) }
{ method(1969) cluster(1462) data(1082) }
{ system(1976) rule(880) can(841) }
{ cancer(2502) breast(956) screen(824) }
{ use(1733) differ(960) four(931) }
{ data(1737) use(1416) pattern(1282) }
{ error(1145) method(1030) estim(1020) }
{ learn(2355) train(1041) set(1003) }
{ clinic(1479) use(1117) guidelin(835) }
{ care(1570) inform(1187) nurs(1089) }
{ patient(2837) hospit(1953) medic(668) }
{ result(1111) use(1088) new(759) }
{ model(3404) distribut(989) bayesian(671) }
{ measur(2081) correl(1212) valu(896) }
{ bind(1733) structur(1185) ligand(1036) }
{ model(2220) cell(1177) simul(1124) }
{ perform(999) metric(946) measur(919) }
{ model(2341) predict(2261) use(1141) }
{ perform(1367) use(1326) method(1137) }
{ health(1844) social(1437) communiti(874) }
{ drug(1928) target(777) effect(648) }
{ implement(1333) system(1263) develop(1122) }
{ process(1125) use(805) approach(778) }
{ can(774) often(719) complex(702) }
{ imag(1947) propos(1133) code(1026) }
{ inform(2794) health(2639) internet(1427) }
{ imag(1057) registr(996) error(939) }
{ sequenc(1873) structur(1644) protein(1328) }
{ method(1219) similar(1157) match(930) }
{ imag(2830) propos(1344) filter(1198) }
{ network(2748) neural(1063) input(814) }
{ imag(2675) segment(2577) method(1081) }
{ patient(2315) diseas(1263) diabet(1191) }
{ take(945) account(800) differ(722) }
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{ surgeri(1148) surgic(1085) robot(1054) }
{ framework(1458) process(801) describ(734) }
{ problem(2511) optim(1539) algorithm(950) }
{ chang(1828) time(1643) increas(1301) }
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{ algorithm(1844) comput(1787) effici(935) }
{ extract(1171) text(1153) clinic(932) }
{ method(1557) propos(1049) approach(1037) }
{ data(1714) softwar(1251) tool(1186) }
{ design(1359) user(1324) use(1319) }
{ control(1307) perform(991) simul(935) }
{ general(901) number(790) one(736) }
{ method(984) reconstruct(947) comput(926) }
{ search(2224) databas(1162) retriev(909) }
{ featur(1941) imag(1645) propos(1176) }
{ case(1353) use(1143) diagnosi(1136) }
{ howev(809) still(633) remain(590) }
{ data(3963) clinic(1234) research(1004) }
{ studi(1410) differ(1259) use(1210) }
{ risk(3053) factor(974) diseas(938) }
{ research(1085) discuss(1038) issu(1018) }
{ system(1050) medic(1026) inform(1018) }
{ import(1318) role(1303) understand(862) }
{ visual(1396) interact(850) tool(830) }
{ studi(1119) effect(1106) posit(819) }
{ blood(1257) pressur(1144) flow(957) }
{ spatial(1525) area(1432) region(1030) }
{ record(1888) medic(1808) patient(1693) }
{ health(3367) inform(1360) care(1135) }
{ model(3480) simul(1196) paramet(876) }
{ monitor(1329) mobil(1314) devic(1160) }
{ ehr(2073) health(1662) electron(1139) }
{ state(1844) use(1261) util(961) }
{ research(1218) medic(880) student(794) }
{ data(2317) use(1299) case(1017) }
{ age(1611) year(1155) adult(843) }
{ medic(1828) order(1363) alert(1069) }
{ signal(2180) analysi(812) frequenc(800) }
{ cost(1906) reduc(1198) effect(832) }
{ group(2977) signific(1463) compar(1072) }
{ sampl(1606) size(1419) use(1276) }
{ gene(2352) biolog(1181) express(1162) }
{ first(2504) two(1366) second(1323) }
{ intervent(3218) particip(2042) group(1664) }
{ activ(1138) subject(705) human(624) }
{ time(1939) patient(1703) rate(768) }
{ patient(1821) servic(1111) care(1106) }
{ use(2086) technolog(871) perceiv(783) }
{ can(981) present(881) function(850) }
{ analysi(2126) use(1163) compon(1037) }
{ structur(1116) can(940) graph(676) }
{ high(1669) rate(1365) level(1280) }
{ use(976) code(926) identifi(902) }
{ survey(1388) particip(1329) question(1065) }
{ estim(2440) model(1874) function(577) }
{ decis(3086) make(1611) patient(1517) }
{ activ(1452) weight(1219) physic(1104) }
{ method(2212) result(1239) propos(1039) }
{ detect(2391) sensit(1101) algorithm(908) }

Resumo

To discover new agents active against methicillin-resistant Staphylococcus aureus (MRSA), in silico models derived from 5451 cell-based anti-MRSA assay data were developed using four machine learning methods, including na?ve Bayesian, support vector machine (SVM), recursive partitioning (RP), and k-nearest neighbors (kNN). A total of 876 models have been constructed based on physicochemical descriptors and fingerprints. The overall predictive accuracies of the best models exceeded 80% for both training and test sets. The best model was employed for the virtual screening of anti-MRSA compounds, which were then validated by a cell-based assay using the broth microdilution method with three types of highly resistant MRSA strains (ST239, ST5, and 252). A total of 12 new anti-MRSA agents were confirmed, which had MIC values ranging from 4 to 64 mg/L. This work proves the capacity of combined multiple ligand-based approaches for the discovery of new agents active against MRSA with cell-based assays. We think this work may inspire other lead identification processes when cell-based assay data are available.

Resumo Limpo

discov new agent activ methicillinresist staphylococcus aureus mrsa silico model deriv cellbas antimrsa assay data develop use four machin learn method includ nave bayesian support vector machin svm recurs partit rp knearest neighbor knn total model construct base physicochem descriptor fingerprint overal predict accuraci best model exceed train test set best model employ virtual screen antimrsa compound valid cellbas assay use broth microdilut method three type high resist mrsa strain st st total new antimrsa agent confirm mic valu rang mgl work prove capac combin multipl ligandbas approach discoveri new agent activ mrsa cellbas assay think work may inspir lead identif process cellbas assay data avail

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