{"id":"https://openalex.org/W2031250359","doi":"https://doi.org/10.1021/ci2004994","title":"Activity-Aware Clustering of High Throughput Screening Data and Elucidation of Orthogonal Structure\u2013Activity Relationships","display_name":"Activity-Aware Clustering of High Throughput Screening Data and Elucidation of Orthogonal Structure\u2013Activity Relationships","publication_year":2011,"publication_date":"2011-11-19","ids":{"openalex":"https://openalex.org/W2031250359","doi":"https://doi.org/10.1021/ci2004994","mag":"2031250359","pmid":"https://pubmed.ncbi.nlm.nih.gov/22098146"},"language":"en","primary_location":{"id":"doi:10.1021/ci2004994","is_oa":false,"landing_page_url":"https://doi.org/10.1021/ci2004994","pdf_url":null,"source":{"id":"https://openalex.org/S167262187","display_name":"Journal of Chemical Information and Modeling","issn_l":"1549-9596","issn":["1549-9596","1549-960X"],"is_oa":false,"is_in_doaj":false,"is_core":true,"host_organization":"https://openalex.org/P4310320006","host_organization_name":"American Chemical Society","host_organization_lineage":["https://openalex.org/P4310320006"],"host_organization_lineage_names":["American Chemical Society"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Chemical Information and Modeling","raw_type":"journal-article"},"type":"article","indexed_in":["crossref","pubmed"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5088290637","display_name":"Eugen Lounkine","orcid":"https://orcid.org/0000-0002-6487-2946"},"institutions":[],"countries":[],"is_corresponding":true,"raw_author_name":"Eugen Lounkine","raw_affiliation_strings":["Novartis Institutes for Biomedical Research, 250 Massachusetts Ave., Cambridge, Massachusetts 02139, United States"],"affiliations":[{"raw_affiliation_string":"Novartis Institutes for Biomedical Research, 250 Massachusetts Ave., Cambridge, Massachusetts 02139, United States","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5059360993","display_name":"Florian Nigsch","orcid":"https://orcid.org/0000-0002-2919-8749"},"institutions":[{"id":"https://openalex.org/I1283582996","display_name":"Novartis (Switzerland)","ror":"https://ror.org/02f9zrr09","country_code":"CH","type":"company","lineage":["https://openalex.org/I1283582996"]},{"id":"https://openalex.org/I4400600974","display_name":"Novartis Institutes for BioMedical Research","ror":"https://ror.org/053gv2m95","country_code":null,"type":"funder","lineage":["https://openalex.org/I1283582996","https://openalex.org/I4400600974"]}],"countries":["CH"],"is_corresponding":false,"raw_author_name":"Florian Nigsch","raw_affiliation_strings":["Novartis Institutes for Biomedical Research, Novartis Campus, Forum 1, CH-4056 Basel, Switzerland"],"affiliations":[{"raw_affiliation_string":"Novartis Institutes for Biomedical Research, Novartis Campus, Forum 1, CH-4056 Basel, Switzerland","institution_ids":["https://openalex.org/I1283582996","https://openalex.org/I4400600974"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5009211876","display_name":"Jeremy L. Jenkins","orcid":"https://orcid.org/0000-0001-9795-0771"},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Jeremy L. Jenkins","raw_affiliation_strings":["Novartis Institutes for Biomedical Research, 250 Massachusetts Ave., Cambridge, Massachusetts 02139, United States"],"affiliations":[{"raw_affiliation_string":"Novartis Institutes for Biomedical Research, 250 Massachusetts Ave., Cambridge, Massachusetts 02139, United States","institution_ids":[]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5110421667","display_name":"Meir Glick","orcid":null},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Meir Glick","raw_affiliation_strings":["Novartis Institutes for Biomedical Research, 250 Massachusetts Ave., Cambridge, Massachusetts 02139, United States"],"affiliations":[{"raw_affiliation_string":"Novartis Institutes for Biomedical Research, 250 Massachusetts Ave., Cambridge, Massachusetts 02139, United States","institution_ids":[]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":4,"corresponding_author_ids":["https://openalex.org/A5088290637"],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":4.3939,"has_fulltext":false,"cited_by_count":22,"citation_normalized_percentile":{"value":0.94763054,"is_in_top_1_percent":false,"is_in_top_10_percent":true},"cited_by_percentile_year":{"min":89,"max":99},"biblio":{"volume":"51","issue":"12","first_page":"3158","last_page":"3168"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10211","display_name":"Computational Drug Discovery Methods","score":1.0,"subfield":{"id":"https://openalex.org/subfields/1703","display_name":"Computational Theory and Mathematics"},"field":{"id":"https://openalex.org/fields/17","display_name":"Computer Science"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},"topics":[{"id":"https://openalex.org/T10211","display_name":"Computational Drug Discovery Methods","score":1.0,"subfield":{"id":"https://openalex.org/subfields/1703","display_name":"Computational Theory and Mathematics"},"field":{"id":"https://openalex.org/fields/17","display_name":"Computer Science"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T10375","display_name":"Pharmacogenetics and Drug Metabolism","score":0.9905999898910522,"subfield":{"id":"https://openalex.org/subfields/3004","display_name":"Pharmacology"},"field":{"id":"https://openalex.org/fields/30","display_name":"Pharmacology, Toxicology and Pharmaceutics"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10252","display_name":"Microbial Natural Products and Biosynthesis","score":0.9782999753952026,"subfield":{"id":"https://openalex.org/subfields/2736","display_name":"Pharmacology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/pubchem","display_name":"PubChem","score":0.8609398603439331},{"id":"https://openalex.org/keywords/pharmacophore","display_name":"Pharmacophore","score":0.7073926329612732},{"id":"https://openalex.org/keywords/cluster-analysis","display_name":"Cluster analysis","score":0.6881811618804932},{"id":"https://openalex.org/keywords/cheminformatics","display_name":"Cheminformatics","score":0.6363901495933533},{"id":"https://openalex.org/keywords/chemical-space","display_name":"Chemical space","score":0.5815711617469788},{"id":"https://openalex.org/keywords/computational-biology","display_name":"Computational biology","score":0.5702002048492432},{"id":"https://openalex.org/keywords/high-throughput-screening","display_name":"High-throughput screening","score":0.502568244934082},{"id":"https://openalex.org/keywords/identification","display_name":"Identification (biology)","score":0.49900126457214355},{"id":"https://openalex.org/keywords/computer-science","display_name":"Computer science","score":0.46685177087783813},{"id":"https://openalex.org/keywords/chembl","display_name":"chEMBL","score":0.44725871086120605},{"id":"https://openalex.org/keywords/virtual-screening","display_name":"Virtual screening","score":0.42090409994125366},{"id":"https://openalex.org/keywords/data-mining","display_name":"Data mining","score":0.4037424921989441},{"id":"https://openalex.org/keywords/drug-discovery","display_name":"Drug discovery","score":0.39761674404144287},{"id":"https://openalex.org/keywords/chemistry","display_name":"Chemistry","score":0.3651031255722046},{"id":"https://openalex.org/keywords/bioinformatics","display_name":"Bioinformatics","score":0.26737189292907715},{"id":"https://openalex.org/keywords/artificial-intelligence","display_name":"Artificial intelligence","score":0.25696346163749695},{"id":"https://openalex.org/keywords/biology","display_name":"Biology","score":0.2065926492214203},{"id":"https://openalex.org/keywords/stereochemistry","display_name":"Stereochemistry","score":0.16439667344093323},{"id":"https://openalex.org/keywords/computational-chemistry","display_name":"Computational chemistry","score":0.14161542057991028}],"concepts":[{"id":"https://openalex.org/C158180186","wikidata":"https://www.wikidata.org/wiki/Q278487","display_name":"PubChem","level":2,"score":0.8609398603439331},{"id":"https://openalex.org/C56173144","wikidata":"https://www.wikidata.org/wiki/Q1539893","display_name":"Pharmacophore","level":2,"score":0.7073926329612732},{"id":"https://openalex.org/C73555534","wikidata":"https://www.wikidata.org/wiki/Q622825","display_name":"Cluster analysis","level":2,"score":0.6881811618804932},{"id":"https://openalex.org/C68762167","wikidata":"https://www.wikidata.org/wiki/Q910164","display_name":"Cheminformatics","level":2,"score":0.6363901495933533},{"id":"https://openalex.org/C99726746","wikidata":"https://www.wikidata.org/wiki/Q906396","display_name":"Chemical space","level":3,"score":0.5815711617469788},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.5702002048492432},{"id":"https://openalex.org/C51323132","wikidata":"https://www.wikidata.org/wiki/Q626251","display_name":"High-throughput screening","level":2,"score":0.502568244934082},{"id":"https://openalex.org/C116834253","wikidata":"https://www.wikidata.org/wiki/Q2039217","display_name":"Identification (biology)","level":2,"score":0.49900126457214355},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.46685177087783813},{"id":"https://openalex.org/C63222358","wikidata":"https://www.wikidata.org/wiki/Q6120337","display_name":"chEMBL","level":3,"score":0.44725871086120605},{"id":"https://openalex.org/C103697762","wikidata":"https://www.wikidata.org/wiki/Q4112105","display_name":"Virtual screening","level":3,"score":0.42090409994125366},{"id":"https://openalex.org/C124101348","wikidata":"https://www.wikidata.org/wiki/Q172491","display_name":"Data mining","level":1,"score":0.4037424921989441},{"id":"https://openalex.org/C74187038","wikidata":"https://www.wikidata.org/wiki/Q1418791","display_name":"Drug discovery","level":2,"score":0.39761674404144287},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.3651031255722046},{"id":"https://openalex.org/C60644358","wikidata":"https://www.wikidata.org/wiki/Q128570","display_name":"Bioinformatics","level":1,"score":0.26737189292907715},{"id":"https://openalex.org/C154945302","wikidata":"https://www.wikidata.org/wiki/Q11660","display_name":"Artificial intelligence","level":1,"score":0.25696346163749695},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.2065926492214203},{"id":"https://openalex.org/C71240020","wikidata":"https://www.wikidata.org/wiki/Q186011","display_name":"Stereochemistry","level":1,"score":0.16439667344093323},{"id":"https://openalex.org/C147597530","wikidata":"https://www.wikidata.org/wiki/Q369472","display_name":"Computational chemistry","level":1,"score":0.14161542057991028},{"id":"https://openalex.org/C59822182","wikidata":"https://www.wikidata.org/wiki/Q441","display_name":"Botany","level":1,"score":0.0}],"mesh":[{"descriptor_ui":"D001499","descriptor_name":"Bayes Theorem","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D001499","descriptor_name":"Bayes Theorem","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D001499","descriptor_name":"Bayes Theorem","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D004364","descriptor_name":"Pharmaceutical Preparations","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D004364","descriptor_name":"Pharmaceutical Preparations","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D004364","descriptor_name":"Pharmaceutical Preparations","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D010600","descriptor_name":"Pharmacology","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D010600","descriptor_name":"Pharmacology","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D010600","descriptor_name":"Pharmacology","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D013329","descriptor_name":"Structure-Activity Relationship","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D013329","descriptor_name":"Structure-Activity Relationship","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D013329","descriptor_name":"Structure-Activity Relationship","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D015195","descriptor_name":"Drug Design","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D015195","descriptor_name":"Drug Design","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D015195","descriptor_name":"Drug Design","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D016000","descriptor_name":"Cluster Analysis","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D016000","descriptor_name":"Cluster Analysis","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D016000","descriptor_name":"Cluster Analysis","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D057166","descriptor_name":"High-Throughput Screening Assays","qualifier_ui":"Q000379","qualifier_name":"methods","is_major_topic":true},{"descriptor_ui":"D057166","descriptor_name":"High-Throughput Screening Assays","qualifier_ui":"Q000379","qualifier_name":"methods","is_major_topic":true},{"descriptor_ui":"D057166","descriptor_name":"High-Throughput Screening Assays","qualifier_ui":"Q000379","qualifier_name":"methods","is_major_topic":true}],"locations_count":2,"locations":[{"id":"doi:10.1021/ci2004994","is_oa":false,"landing_page_url":"https://doi.org/10.1021/ci2004994","pdf_url":null,"source":{"id":"https://openalex.org/S167262187","display_name":"Journal of Chemical Information and Modeling","issn_l":"1549-9596","issn":["1549-9596","1549-960X"],"is_oa":false,"is_in_doaj":false,"is_core":true,"host_organization":"https://openalex.org/P4310320006","host_organization_name":"American Chemical Society","host_organization_lineage":["https://openalex.org/P4310320006"],"host_organization_lineage_names":["American Chemical Society"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Chemical Information and Modeling","raw_type":"journal-article"},{"id":"pmid:22098146","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/22098146","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of chemical information and modeling","raw_type":null}],"best_oa_location":null,"sustainable_development_goals":[],"awards":[],"funders":[{"id":"https://openalex.org/F4320333796","display_name":"Novartis Institutes for BioMedical Research","ror":null}],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":40,"referenced_works":["https://openalex.org/W156509570","https://openalex.org/W1549626617","https://openalex.org/W1965341570","https://openalex.org/W1975323048","https://openalex.org/W1977934535","https://openalex.org/W1978229532","https://openalex.org/W1979845492","https://openalex.org/W1983332050","https://openalex.org/W1984678368","https://openalex.org/W1988037271","https://openalex.org/W1989337891","https://openalex.org/W2001565801","https://openalex.org/W2006322600","https://openalex.org/W2012411415","https://openalex.org/W2014811102","https://openalex.org/W2015122936","https://openalex.org/W2019063733","https://openalex.org/W2028326521","https://openalex.org/W2040030948","https://openalex.org/W2040135138","https://openalex.org/W2041946761","https://openalex.org/W2046581055","https://openalex.org/W2046588282","https://openalex.org/W2049360806","https://openalex.org/W2056881083","https://openalex.org/W2060531713","https://openalex.org/W2073392404","https://openalex.org/W2078295062","https://openalex.org/W2085126686","https://openalex.org/W2085398335","https://openalex.org/W2099536767","https://openalex.org/W2132842501","https://openalex.org/W2149150765","https://openalex.org/W2159907048","https://openalex.org/W2160114756","https://openalex.org/W2179066627","https://openalex.org/W2196714401","https://openalex.org/W2320034101","https://openalex.org/W2409278974","https://openalex.org/W4254171776"],"related_works":["https://openalex.org/W2780675302","https://openalex.org/W2172072929","https://openalex.org/W2896688061","https://openalex.org/W4313503466","https://openalex.org/W2415234544","https://openalex.org/W4234348296","https://openalex.org/W2812842313","https://openalex.org/W2151971404","https://openalex.org/W2887866551","https://openalex.org/W4281381646"],"abstract_inverted_index":{"From":[0],"a":[1,65,149,156,246,280],"medicinal":[2,120],"chemistry":[3],"point":[4],"of":[5,8,12,23,36,56,68,74,163,211,223,230,235,265],"view,":[6],"one":[7],"the":[9,21,37,57,98,106,119,161,172,179,194,224,236,272],"primary":[10,38],"goals":[11],"high":[13],"throughput":[14],"screening":[15],"(HTS)":[16],"hit":[17,275],"list":[18,276],"assessment":[19,277],"is":[20,53,259],"identification":[22,234],"chemotypes":[24,32,124],"with":[25],"an":[26],"informative":[27],"structure-activity":[28],"relationship":[29],"(SAR).":[30],"Such":[31],"may":[33,131,269],"enable":[34],"optimization":[35],"potency,":[39],"as":[40,42],"well":[41],"selectivity":[43],"and":[44,77,109,143,146,154,249,268,278],"phamacokinetic":[45],"properties.":[46],"A":[47,227],"common":[48,123],"way":[49],"to":[50,81,115,129,262],"prioritize":[51],"them":[52],"molecular":[54,82,141,188],"clustering":[55,60,152,184],"hits.":[58],"Typical":[59],"techniques,":[61],"however,":[62],"rely":[63],"on":[64,174],"general":[66],"notion":[67],"chemical":[69,137],"similarity":[70,142],"or":[71,196],"standard":[72],"rules":[73],"scaffold":[75],"decomposition":[76],"are":[78,85,111,126],"thus":[79,110],"insensitive":[80],"features":[83],"that":[84,125,190,220],"enriched":[86],"in":[87,105,167,207,218],"biologically":[88],"active":[89],"compounds.":[90,169],"This":[91],"hinders":[92],"SAR":[93,165],"analysis,":[94],"because":[95],"compounds":[96,186],"sharing":[97,187],"same":[99,107],"pharmacophore":[100],"might":[101],"not":[102,112,127],"end":[103],"up":[104],"cluster":[108],"directly":[113],"compared":[114],"each":[116],"other":[117],"by":[118],"chemist.":[121],"Similarly,":[122],"related":[128],"activity":[130,266],"contaminate":[132],"clusters,":[133],"distracting":[134],"from":[135,178],"important":[136],"motifs.":[138],"We":[139,170],"combined":[140],"Bayesian":[144],"models":[145],"introduce":[147],"(I)":[148],"robust,":[150],"activity-aware":[151],"approach":[153],"(II)":[155],"feature":[157],"mapping":[158],"method":[159,173,256],"for":[160,193,233,239],"elucidation":[162],"distinct":[164,242],"determinants":[166],"polypharmacologic":[168],"evaluated":[171],"462":[175],"dose-response":[176],"assays":[177],"Pubchem":[180],"Bioassay":[181],"repository.":[182],"Activity-aware":[183],"grouped":[185],"cores":[189,231],"were":[191],"specific":[192],"target":[195],"pathway":[197],"at":[198],"hand,":[199],"rather":[200],"than":[201],"grouping":[202],"inactive":[203],"scaffolds":[204],"commonly":[205],"found":[206,217],"compound":[208],"series.":[209],"Many":[210],"these":[212],"core":[213],"structures":[214],"we":[215],"also":[216],"literature":[219],"discussed":[221],"SARs":[222],"respective":[225],"targets.":[226],"numerical":[228],"comparison":[229],"allowed":[232],"structural":[237],"prerequisites":[238],"polypharmacology,":[240],"i.e.,":[241],"bioactive":[243],"regions":[244],"within":[245],"single":[247],"compound,":[248],"pointed":[250],"toward":[251],"selectivity-conferring":[252],"medchem":[253,281],"strategies.":[254],"The":[255],"presented":[257],"here":[258],"generally":[260],"applicable":[261],"any":[263],"type":[264],"data":[267],"help":[270],"bridge":[271],"gap":[273],"between":[274],"designing":[279],"strategy.":[282]},"counts_by_year":[{"year":2024,"cited_by_count":2},{"year":2022,"cited_by_count":1},{"year":2020,"cited_by_count":2},{"year":2016,"cited_by_count":2},{"year":2015,"cited_by_count":1},{"year":2014,"cited_by_count":4},{"year":2013,"cited_by_count":7},{"year":2012,"cited_by_count":3}],"updated_date":"2025-11-06T03:46:38.306776","created_date":"2025-10-10T00:00:00"}