J Chem Inf Model - Optimizing predictive performance of CASE Ultra expert system models using the applicability domains of individual toxicity alerts.

Tópicos

{ model(2656) set(1616) predict(1553) }
{ clinic(1479) use(1117) guidelin(835) }
{ structur(1116) can(940) graph(676) }
{ compound(1573) activ(1297) structur(1058) }
{ concept(1167) ontolog(924) domain(897) }
{ medic(1828) order(1363) alert(1069) }
{ can(774) often(719) complex(702) }
{ visual(1396) interact(850) tool(830) }
{ studi(1410) differ(1259) use(1210) }
{ cost(1906) reduc(1198) effect(832) }
{ detect(2391) sensit(1101) algorithm(908) }
{ perform(1367) use(1326) method(1137) }
{ control(1307) perform(991) simul(935) }
{ process(1125) use(805) approach(778) }
{ spatial(1525) area(1432) region(1030) }
{ data(1737) use(1416) pattern(1282) }
{ take(945) account(800) differ(722) }
{ chang(1828) time(1643) increas(1301) }
{ algorithm(1844) comput(1787) effici(935) }
{ method(1557) propos(1049) approach(1037) }
{ search(2224) databas(1162) retriev(909) }
{ case(1353) use(1143) diagnosi(1136) }
{ model(2341) predict(2261) use(1141) }
{ activ(1138) subject(705) human(624) }
{ survey(1388) particip(1329) question(1065) }
{ activ(1452) weight(1219) physic(1104) }
{ inform(2794) health(2639) internet(1427) }
{ howev(809) still(633) remain(590) }
{ research(1085) discuss(1038) issu(1018) }
{ blood(1257) pressur(1144) flow(957) }
{ monitor(1329) mobil(1314) devic(1160) }
{ state(1844) use(1261) util(961) }
{ data(2317) use(1299) case(1017) }
{ signal(2180) analysi(812) frequenc(800) }
{ can(981) present(881) function(850) }
{ high(1669) rate(1365) level(1280) }
{ use(976) code(926) identifi(902) }
{ use(1733) differ(960) four(931) }
{ drug(1928) target(777) effect(648) }
{ model(3404) distribut(989) bayesian(671) }
{ imag(1947) propos(1133) code(1026) }
{ system(1976) rule(880) can(841) }
{ measur(2081) correl(1212) valu(896) }
{ imag(1057) registr(996) error(939) }
{ bind(1733) structur(1185) ligand(1036) }
{ sequenc(1873) structur(1644) protein(1328) }
{ method(1219) similar(1157) match(930) }
{ featur(3375) classif(2383) classifi(1994) }
{ imag(2830) propos(1344) filter(1198) }
{ network(2748) neural(1063) input(814) }
{ imag(2675) segment(2577) method(1081) }
{ patient(2315) diseas(1263) diabet(1191) }
{ studi(2440) review(1878) systemat(933) }
{ motion(1329) object(1292) video(1091) }
{ assess(1506) score(1403) qualiti(1306) }
{ treatment(1704) effect(941) patient(846) }
{ surgeri(1148) surgic(1085) robot(1054) }
{ framework(1458) process(801) describ(734) }
{ problem(2511) optim(1539) algorithm(950) }
{ error(1145) method(1030) estim(1020) }
{ learn(2355) train(1041) set(1003) }
{ extract(1171) text(1153) clinic(932) }
{ data(1714) softwar(1251) tool(1186) }
{ design(1359) user(1324) use(1319) }
{ model(2220) cell(1177) simul(1124) }
{ care(1570) inform(1187) nurs(1089) }
{ general(901) number(790) one(736) }
{ method(984) reconstruct(947) comput(926) }
{ featur(1941) imag(1645) propos(1176) }
{ data(3963) clinic(1234) research(1004) }
{ risk(3053) factor(974) diseas(938) }
{ perform(999) metric(946) measur(919) }
{ system(1050) medic(1026) inform(1018) }
{ import(1318) role(1303) understand(862) }
{ studi(1119) effect(1106) posit(819) }
{ record(1888) medic(1808) patient(1693) }
{ health(3367) inform(1360) care(1135) }
{ model(3480) simul(1196) paramet(876) }
{ ehr(2073) health(1662) electron(1139) }
{ research(1218) medic(880) student(794) }
{ patient(2837) hospit(1953) medic(668) }
{ age(1611) year(1155) adult(843) }
{ group(2977) signific(1463) compar(1072) }
{ sampl(1606) size(1419) use(1276) }
{ gene(2352) biolog(1181) express(1162) }
{ data(3008) multipl(1320) sourc(1022) }
{ first(2504) two(1366) second(1323) }
{ intervent(3218) particip(2042) group(1664) }
{ time(1939) patient(1703) rate(768) }
{ patient(1821) servic(1111) care(1106) }
{ use(2086) technolog(871) perceiv(783) }
{ analysi(2126) use(1163) compon(1037) }
{ health(1844) social(1437) communiti(874) }
{ cancer(2502) breast(956) screen(824) }
{ result(1111) use(1088) new(759) }
{ implement(1333) system(1263) develop(1122) }
{ estim(2440) model(1874) function(577) }
{ decis(3086) make(1611) patient(1517) }
{ method(1969) cluster(1462) data(1082) }
{ method(2212) result(1239) propos(1039) }

Resumo

Fragment based expert system models of toxicological end points are primarily comprised of a set of substructures that are statistically related to the toxic property in question. These special substructures are often referred to as toxicity alerts, toxicophores, or biophores. They are the main building blocks/classifying units of the model, and it is important to define the chemical structural space within which the alerts are expected to produce reliable predictions. Furthermore, defining an appropriate applicability domain is required as part of the OECD guidelines for the validation of quantitative structure-activity relationships (QSARs). In this respect, this paper describes a method to construct applicability domains for individual toxicity alerts that are part of the CASE Ultra expert system models. Defining applicability domain for individual alerts was necessary because each CASE Ultra model is comprised of multiple alerts, and different alerts of a model usually represent different toxicity mechanisms and cover different structural space; the use of an applicability domain for the overall model is often not adequate. The domain for each alert was constructed using a set of fragments that were found to be statistically related to the end point in question as opposed to using overall structural similarity or physicochemical properties. Use of the applicability domains in reducing false positive predictions is demonstrated. It is now possible to obtain ROC (receiver operating characteristic) profiles of CASE Ultra models by applying domain adherence cutoffs on the alerts identified in test chemicals. This helps in optimizing the performance of a model based on their true positive-false positive prediction trade-offs and reduce drastic effects on the predictive performance caused by the active/inactive ratio of the model's training set. None of the major currently available commercial expert systems for toxicity prediction offer the possibility to explore a model's full range of sensitivity-specificity spectrum, and therefore, the methodology developed in this study can be of benefit in improving the predictive ability of the alert based expert systems.

Resumo Limpo

fragment base expert system model toxicolog end point primarili compris set substructur statist relat toxic properti question special substructur often refer toxic alert toxicophor biophor main build blocksclassifi unit model import defin chemic structur space within alert expect produc reliabl predict furthermor defin appropri applic domain requir part oecd guidelin valid quantit structureact relationship qsar respect paper describ method construct applic domain individu toxic alert part case ultra expert system model defin applic domain individu alert necessari case ultra model compris multipl alert differ alert model usual repres differ toxic mechan cover differ structur space use applic domain overal model often adequ domain alert construct use set fragment found statist relat end point question oppos use overal structur similar physicochem properti use applic domain reduc fals posit predict demonstr now possibl obtain roc receiv oper characterist profil case ultra model appli domain adher cutoff alert identifi test chemic help optim perform model base true positivefals posit predict tradeoff reduc drastic effect predict perform caus activeinact ratio model train set none major current avail commerci expert system toxic predict offer possibl explor model full rang sensitivityspecif spectrum therefor methodolog develop studi can benefit improv predict abil alert base expert system

Resumos Similares

BMC Med Inform Decis Mak - Regression tree construction by bootstrap: model search for DRG-systems applied to Austrian health-data. ( 0,786617491035712 )
J Chem Inf Model - Statistical analysis and compound selection of combinatorial libraries for soluble epoxide hydrolase. ( 0,75995011397164 )
J Chem Inf Model - In silico prediction of total human plasma clearance. ( 0,743802846629853 )
J Chem Inf Model - Analysis and study of molecule data sets using snowflake diagrams of weighted maximum common subgraph trees. ( 0,679560568458544 )
J Chem Inf Model - Time-split cross-validation as a method for estimating the goodness of prospective prediction. ( 0,663156730601263 )
J Chem Inf Model - Revisiting the general solubility equation: in silico prediction of aqueous solubility incorporating the effect of topographical polar surface area. ( 0,653180483194087 )
J Chem Inf Model - Applicability Domain ANalysis (ADAN): a robust method for assessing the reliability of drug property predictions. ( 0,650726161820272 )
J Chem Inf Model - Pharmacophore assessment through 3-D QSAR: evaluation of the predictive ability on new derivatives by the application on a series of antitubercular agents. ( 0,644344057408668 )
AMIA Annu Symp Proc - Order sets in computerized physician order entry systems: an analysis of seven sites. ( 0,640977108553741 )
J Chem Inf Model - In silico prediction of aqueous solubility using simple QSPR models: the importance of phenol and phenol-like moieties. ( 0,638808784714893 )
Curr Comput Aided Drug Des - QSAR Models for the Reactivation of Sarin Inhibited AChE by Quaternary Pyridinium Oximes Based on Monte Carlo Method. ( 0,634447496860803 )
Artif Intell Med - Training artificial neural networks directly on the concordance index for censored data using genetic algorithms. ( 0,633304726999116 )
BMC Med Inform Decis Mak - Measuring preferences for analgesic treatment for cancer pain: how do African-Americans and Whites perform on choice-based conjoint (CBC) analysis experiments? ( 0,625161553127089 )
BMC Med Inform Decis Mak - Concordance and predictive value of two adverse drug event data sets. ( 0,621540741570647 )
J Chem Inf Model - Prediction of linear cationic antimicrobial peptides based on characteristics responsible for their interaction with the membranes. ( 0,621263144893669 )
J Chem Inf Model - Experimental and computational prediction of glass transition temperature of drugs. ( 0,62023470957582 )
J Chem Inf Model - Design and synthesis of new antioxidants predicted by the model developed on a set of pulvinic acid derivatives. ( 0,619522725298056 )
J Chem Inf Model - Coping with unbalanced class data sets in oral absorption models. ( 0,615995487456485 )
J Chem Inf Model - Binary classification of a large collection of environmental chemicals from estrogen receptor assays by quantitative structure-activity relationship and machine learning methods. ( 0,615166074528612 )
J Chem Inf Model - Classification of compounds with distinct or overlapping multi-target activities and diverse molecular mechanisms using emerging chemical patterns. ( 0,615025470247753 )
J Chem Inf Model - How accurately can we predict the melting points of drug-like compounds? ( 0,614946039262759 )
J Chem Inf Model - Automated building of organometallic complexes from 3D fragments. ( 0,614807667633907 )
J Chem Inf Model - Predicting pK(a) values of substituted phenols from atomic charges: comparison of different quantum mechanical methods and charge distribution schemes. ( 0,614472189651522 )
J Chem Inf Model - Hsp90 inhibitors, part 1: definition of 3-D QSAutogrid/R models as a tool for virtual screening. ( 0,60901658819289 )
J Chem Inf Model - A multiscale simulation system for the prediction of drug-induced cardiotoxicity. ( 0,602217123149835 )
J Chem Inf Model - Three useful dimensions for domain applicability in QSAR models using random forest. ( 0,599789688566164 )
J Chem Inf Model - GRID-based three-dimensional pharmacophores II: PharmBench, a benchmark data set for evaluating pharmacophore elucidation methods. ( 0,597106836329264 )
AMIA Annu Symp Proc - Effect of data combination on predictive modeling: a study using gene expression data. ( 0,596301440324595 )
J Chem Inf Model - iLOGP: a simple, robust, and efficient description of n-octanol/water partition coefficient for drug design using the GB/SA approach. ( 0,593209959568407 )
Comput Methods Programs Biomed - Kinetic modelling of haemodialysis removal of myoglobin in rhabdomyolysis patients. ( 0,592642120259548 )
J Chem Inf Model - Does rational selection of training and test sets improve the outcome of QSAR modeling? ( 0,592330292695412 )
J Chem Inf Model - Study of chromatographic retention of natural terpenoids by chemoinformatic tools. ( 0,589713050043353 )
J Chem Inf Model - Predictions of BuChE inhibitors using support vector machine and naive Bayesian classification techniques in drug discovery. ( 0,587872122523418 )
J Chem Inf Model - In silico prediction of chemical acute oral toxicity using multi-classification methods. ( 0,587640895385013 )
AMIA Annu Symp Proc - Motivating the additional use of external validity: examining transportability in a model of glioblastoma multiforme. ( 0,587519603678462 )
J. Comput. Biol. - The complexity of the dirichlet model for multiple alignment data. ( 0,586310760485822 )
J Chem Inf Model - Rank order entropy: why one metric is not enough. ( 0,585672930401837 )
Comput. Biol. Med. - A prediction model of substrates and non-substrates of breast cancer resistance protein (BCRP) developed by GA-CG-SVM method. ( 0,584947088910054 )
Med Biol Eng Comput - Optimal design of clinical tests for the identification of physiological models of type 1 diabetes in the presence of model mismatch. ( 0,584816408635503 )
J Chem Inf Model - A comparison of different QSAR approaches to modeling CYP450 1A2 inhibition. ( 0,584433296254255 )
J Chem Inf Model - Beyond the scope of Free-Wilson analysis: building interpretable QSAR models with machine learning algorithms. ( 0,581335187994902 )
J Am Med Inform Assoc - Harvest: an open platform for developing web-based biomedical data discovery and reporting applications. ( 0,580042764548869 )
IEEE Trans Image Process - Incremental N-mode SVD for large-scale multilinear generative models. ( 0,579946578022363 )
J Chem Inf Model - PLS-optimal: a stepwise D-optimal design based on latent variables. ( 0,578707541778652 )
J. Comput. Biol. - Big cat phylogenies, consensus trees, and computational thinking. ( 0,573392621670321 )
J Am Med Inform Assoc - Drug repurposing: mining protozoan proteomes for targets of known bioactive compounds. ( 0,573271855802095 )
Artif Intell Med - Fuzzy model identification of dengue epidemic in Colombia based on multiresolution analysis. ( 0,572974288230208 )
Comput Math Methods Med - Multiscale autoregressive identification of neuroelectrophysiological systems. ( 0,571776168625763 )
J Chem Inf Model - Oversampling to overcome overfitting: exploring the relationship between data set composition, molecular descriptors, and predictive modeling methods. ( 0,571725170712099 )
J Chem Inf Model - A new approach to radial basis function approximation and its application to QSAR. ( 0,571379210460866 )
Int J Health Geogr - Incorporating geographical factors with artificial neural networks to predict reference values of erythrocyte sedimentation rate. ( 0,570599556161559 )
Artif Intell Med - A machine learning-based approach to prognostic analysis of thoracic transplantations. ( 0,567940636589241 )
AMIA Annu Symp Proc - Advanced proficiency EHR training: effect on physicians' EHR efficiency, EHR satisfaction and job satisfaction. ( 0,567525559256651 )
J Chem Inf Model - In silico prediction of chemical Ames mutagenicity. ( 0,566135646597103 )
AMIA Annu Symp Proc - Ontology-based federated data access to human studies information. ( 0,563448099804192 )
J Chem Inf Model - RS-Predictor models augmented with SMARTCyp reactivities: robust metabolic regioselectivity predictions for nine CYP isozymes. ( 0,560974916828624 )
AMIA Annu Symp Proc - Predicting the dengue incidence in Singapore using univariate time series models. ( 0,560237545323892 )
J Chem Inf Model - Synthesis, bioassay, and molecular field topology analysis of diverse vasodilatory heterocycles. ( 0,56011809224962 )
J Chem Inf Model - Profile-QSAR and Surrogate AutoShim protein-family modeling of proteases. ( 0,557951953152063 )
AMIA Annu Symp Proc - Identifying Deviations from Usual Medical Care using a Statistical Approach. ( 0,556145844243422 )
J Chem Inf Model - CSAR data set release 2012: ligands, affinities, complexes, and docking decoys. ( 0,552197547174756 )
J Chem Inf Model - Comparative studies on some metrics for external validation of QSPR models. ( 0,551319628790578 )
Comput. Biol. Med. - Quantification of contributions of molecular fragments for eye irritation of organic chemicals using QSAR study. ( 0,549124228319493 )
J Chem Inf Model - Quantitative structure-activity relationship models of clinical pharmacokinetics: clearance and volume of distribution. ( 0,547847221022837 )
J Chem Inf Model - Construction and use of fragment-augmented molecular Hasse diagrams. ( 0,54750992698856 )
Int J Health Geogr - Comparative analysis of remotely-sensed data products via ecological niche modeling of avian influenza case occurrences in Middle Eastern poultry. ( 0,546710841261002 )
J Biomed Inform - MysiRNA: improving siRNA efficacy prediction using a machine-learning model combining multi-tools and whole stacking energy (G). ( 0,545806060294331 )
J Chem Inf Model - Generative topographic mapping-based classification models and their applicability domain: application to the biopharmaceutics Drug Disposition Classification System (BDDCS). ( 0,544320709293982 )
Spat Spatiotemporal Epidemiol - Spatial modelling of disease using data- and knowledge-driven approaches. ( 0,543987548871931 )
J Chem Inf Model - Profile-QSAR: a novel meta-QSAR method that combines activities across the kinase family to accurately predict affinity, selectivity, and cellular activity. ( 0,543654173743894 )
J Biomed Inform - Interoperability of clinical decision-support systems and electronic health records using archetypes: a case study in clinical trial eligibility. ( 0,542201995986412 )
Geospat Health - Indirect field technology for detecting areas object of illegal spills harmful to human health: application of drones, photogrammetry and hydrological models. ( 0,541854047157252 )
Comput Biol Chem - Homology modeling, binding site identification and docking in flavone hydroxylase CYP105P2 in Streptomyces peucetius ATCC 27952. ( 0,540015067083591 )
Int J Comput Assist Radiol Surg - Assessing performance in brain tumor resection using a novel virtual reality simulator. ( 0,539577065328847 )
Comput. Biol. Med. - Artificial neural network modelling of the results of tympanoplasty in chronic suppurative otitis media patients. ( 0,53833808076538 )
J Chem Inf Model - Mapping monomeric threading to protein-protein structure prediction. ( 0,537341246501375 )
J Chem Inf Model - How experimental errors influence drug metabolism and pharmacokinetic QSAR/QSPR models. ( 0,534226079444873 )
Comput Methods Programs Biomed - A predictive model of longitudinal, patient-specific colonoscopy results. ( 0,532785618968781 )
J Chem Inf Model - Estimation of carcinogenicity using molecular fragments tree. ( 0,53225377152092 )
J. Comput. Biol. - Counting RNA pseudoknotted structures. ( 0,531183385014872 )
J Chem Inf Model - Development of novel 3D-QSAR combination approach for screening and optimizing B-Raf inhibitors in silico. ( 0,530440342794889 )
J Chem Inf Model - Discovery of novel antimalarial compounds enabled by QSAR-based virtual screening. ( 0,529967228048726 )
J Chem Inf Model - Hsp90 inhibitors, part 2: combining ligand-based and structure-based approaches for virtual screening application. ( 0,529631771126868 )
J Chem Inf Model - Best of both worlds: combining pharma data and state of the art modeling technology to improve in Silico pKa prediction. ( 0,529381955676197 )
J Chem Inf Model - Binary classification of aqueous solubility using support vector machines with reduction and recombination feature selection. ( 0,526824498808451 )
BMC Med Inform Decis Mak - Validating archetypes for the Multiple Sclerosis Functional Composite. ( 0,525695387046545 )
J Chem Inf Model - Quantitative structure-activity relationship models for ready biodegradability of chemicals. ( 0,524851746888718 )
J Chem Inf Model - Prediction of compound potency changes in matched molecular pairs using support vector regression. ( 0,523066276896963 )
Lifetime Data Anal - Analysis of cure rate survival data under proportional odds model. ( 0,522918324819877 )
J Chem Inf Model - Combined 3D-QSAR, molecular docking, and molecular dynamics study on piperazinyl-glutamate-pyridines/pyrimidines as potent P2Y12 antagonists for inhibition of platelet aggregation. ( 0,522798628665138 )
J Chem Inf Model - Applicability domain based on ensemble learning in classification and regression analyses. ( 0,522356507840827 )
J Chem Inf Model - Template CoMFA: the 3D-QSAR Grail? ( 0,521292839809949 )
Comput. Aided Surg. - Evaluation of a computational model to predict elbow range of motion. ( 0,521170917048629 )
J Chem Inf Model - Molecular modeling of the 3D structure of 5-HT(1A)R: discovery of novel 5-HT(1A)R agonists via dynamic pharmacophore-based virtual screening. ( 0,518308421863704 )
J Chem Inf Model - Impact of template choice on homology model efficiency in virtual screening. ( 0,518189518838668 )
J Chem Inf Model - Rationalization of the pKa values of alcohols and thiols using atomic charge descriptors and its application to the prediction of amino acid pKa's. ( 0,517863021221575 )
Int J Med Inform - Design and implementation of I2Vote--an interactive image-based voting system using windows mobile devices. ( 0,517862472601543 )
J Chem Inf Model - Four-dimensional structure-activity relationship model to predict HIV-1 integrase strand transfer inhibition using LQTA-QSAR methodology. ( 0,515922302036447 )
J Chem Inf Model - FAst MEtabolizer (FAME): A rapid and accurate predictor of sites of metabolism in multiple species by endogenous enzymes. ( 0,515212026388096 )
J Chem Inf Model - Harvesting classification trees for drug discovery. ( 0,515102957227372 )