{"id":"https://openalex.org/W6950643201","doi":"https://doi.org/10.5281/zenodo.7358736","title":"Leveraging biochemical reactions to unravel functional impacts of cancer somatic variants affecting protein interaction interfaces","display_name":"Leveraging biochemical reactions to unravel functional impacts of cancer somatic variants affecting protein interaction interfaces","publication_year":2022,"publication_date":"2022-11-24","ids":{"openalex":"https://openalex.org/W6950643201","doi":"https://doi.org/10.5281/zenodo.7358736"},"language":"en","primary_location":{"id":"doi:10.5281/zenodo.7358736","doi":"https://doi.org/10.5281/zenodo.7358736","is_oa":true,"landing_page_url":"https://doi.org/10.5281/zenodo.7358736","pdf_url":null,"source":{"id":"https://openalex.org/S4306400562","display_name":"Zenodo (CERN European Organization for Nuclear Research)","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I67311998","host_organization_name":"European Organization for Nuclear Research","host_organization_lineage":["https://openalex.org/I67311998"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":null,"is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"JournalArticle"},"volume":null,"type":"article","indexed_in":["datacite"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://doi.org/10.5281/zenodo.7358736","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":null,"display_name":"Raimondi, Francesco","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I157210198","display_name":"Scuola Normale Superiore","ror":"https://ror.org/03aydme10","country_code":"IT","type":"education","lineage":["https://openalex.org/I157210198"]}],"countries":["IT"],"is_corresponding":false,"raw_author_name":"Raimondi, Francesco","raw_affiliation_strings":["Laboratorio di Biologia Bio@SNS, Scuola Normale Superiore, Pisa 56126, Italy"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Laboratorio di Biologia Bio@SNS, Scuola Normale Superiore, Pisa 56126, Italy","institution_ids":["https://openalex.org/I157210198"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5075883686","display_name":"Joshua G. Burkhart","orcid":"https://orcid.org/0000-0001-9279-1556","observed_orcids":["https://orcid.org/0000-0001-9279-1556"]},"institutions":[{"id":"https://openalex.org/I165690674","display_name":"Oregon Health & Science University","ror":"https://ror.org/009avj582","country_code":"US","type":"education","lineage":["https://openalex.org/I165690674"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Burkhart, Joshua G","raw_affiliation_strings":["Division of Bioinformatics and Computational Biology, Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, OR, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Bioinformatics and Computational Biology, Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, OR, USA","institution_ids":["https://openalex.org/I165690674"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5040703948","display_name":"Matthew J. Betts","orcid":"https://orcid.org/0000-0003-4583-9814","observed_orcids":["https://orcid.org/0000-0003-4583-9814"]},"institutions":[{"id":"https://openalex.org/I223822909","display_name":"Heidelberg University","ror":"https://ror.org/038t36y30","country_code":"DE","type":"education","lineage":["https://openalex.org/I223822909"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Betts, Matthew J","raw_affiliation_strings":["Heidelberg University Biochemistry Center, Heidelberg 69120, Germany"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Heidelberg University Biochemistry Center, Heidelberg 69120, Germany","institution_ids":["https://openalex.org/I223822909"]}]},{"author_position":"middle","author":{"id":null,"display_name":"Russell, Robert B","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I223822909","display_name":"Heidelberg University","ror":"https://ror.org/038t36y30","country_code":"DE","type":"education","lineage":["https://openalex.org/I223822909"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Russell, Robert B","raw_affiliation_strings":["Heidelberg University Biochemistry Center, Heidelberg 69120, Germany"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Heidelberg University Biochemistry Center, Heidelberg 69120, Germany","institution_ids":["https://openalex.org/I223822909"]}]},{"author_position":"last","author":{"id":null,"display_name":"Wu, Guanming","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I165690674","display_name":"Oregon Health & Science University","ror":"https://ror.org/009avj582","country_code":"US","type":"education","lineage":["https://openalex.org/I165690674"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Wu, Guanming","raw_affiliation_strings":["Division of Bioinformatics and Computational Biology, Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, OR, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Bioinformatics and Computational Biology, Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, OR, USA","institution_ids":["https://openalex.org/I165690674"]}]}],"institutions":[],"countries_distinct_count":3,"institutions_distinct_count":3,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":0.0815,"has_fulltext":false,"cited_by_count":2,"citation_normalized_percentile":{"value":0.3186138,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":88,"max":93},"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":true,"primary_topic":{"id":"https://openalex.org/T10887","display_name":"Bioinformatics and Genomic Networks","score":0.9154999852180481,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T10887","display_name":"Bioinformatics and Genomic Networks","score":0.9154999852180481,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T11287","display_name":"Cancer Genomics and Diagnostics","score":0.07029999792575836,"subfield":{"id":"https://openalex.org/subfields/1306","display_name":"Cancer Research"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T11642","display_name":"Genomics and Rare Diseases","score":0.004600000102072954,"subfield":{"id":"https://openalex.org/subfields/1311","display_name":"Genetics"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/protein-protein-interfaces","display_name":"protein-protein interfaces","score":0.7630000114440918},{"id":"https://openalex.org/keywords/biochemical-reactions","display_name":"biochemical reactions","score":0.9769999980926514},{"id":"https://openalex.org/keywords/reactome","display_name":"Reactome","score":0.8569999933242798},{"id":"https://openalex.org/keywords/rare-mutations","display_name":"rare mutations","score":0.7680000066757202},{"id":"https://openalex.org/keywords/patient-stratification","display_name":"patient stratification","score":0.6729999780654907},{"id":"https://openalex.org/keywords/survival-time","display_name":"survival time","score":0.7350000143051147},{"id":"https://openalex.org/keywords/g-protein-coupled-receptor-signaling","display_name":"G protein-coupled receptor signaling","score":0.8389999866485596},{"id":"https://openalex.org/keywords/pik3ca","display_name":"PIK3CA","score":0.8799999952316284},{"id":"https://openalex.org/keywords/complement-system","display_name":"complement system","score":0.8849999904632568},{"id":"https://openalex.org/keywords/personalized-medicine","display_name":"personalized medicine","score":0.4729999899864197},{"id":"https://openalex.org/keywords/multiscale-analysis","display_name":"multiscale analysis","score":0.5609999895095825}],"concepts":[{"id":"https://openalex.org/C10679952","wikidata":"https://www.wikidata.org/wiki/Q5308937","display_name":"Druggability","level":3,"score":0.7871000170707703},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.6732000112533569},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.6628999710083008},{"id":"https://openalex.org/C2779343474","wikidata":"https://www.wikidata.org/wiki/Q3109175","display_name":"Context (archaeology)","level":2,"score":0.6140000224113464},{"id":"https://openalex.org/C11804247","wikidata":"https://www.wikidata.org/wiki/Q896177","display_name":"Protein\u2013protein interaction","level":2,"score":0.5311999917030334},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.48030000925064087},{"id":"https://openalex.org/C127716648","wikidata":"https://www.wikidata.org/wiki/Q104053","display_name":"Phenotype","level":3,"score":0.44609999656677246},{"id":"https://openalex.org/C134305767","wikidata":"https://www.wikidata.org/wiki/Q725508","display_name":"Somatic cell","level":3,"score":0.40230000019073486},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.3783000111579895},{"id":"https://openalex.org/C2909613950","wikidata":"https://www.wikidata.org/wiki/Q158695","display_name":"Protein Interaction Networks","level":3,"score":0.33880001306533813},{"id":"https://openalex.org/C60644358","wikidata":"https://www.wikidata.org/wiki/Q128570","display_name":"Bioinformatics","level":1,"score":0.31700000166893005},{"id":"https://openalex.org/C152662350","wikidata":"https://www.wikidata.org/wiki/Q815297","display_name":"Systems biology","level":2,"score":0.31380000710487366},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.30469998717308044},{"id":"https://openalex.org/C2986374874","wikidata":"https://www.wikidata.org/wiki/Q8054","display_name":"Protein function","level":3,"score":0.30239999294281006},{"id":"https://openalex.org/C9927688","wikidata":"https://www.wikidata.org/wiki/Q4915012","display_name":"Biological pathway","level":4,"score":0.29989999532699585},{"id":"https://openalex.org/C501734568","wikidata":"https://www.wikidata.org/wiki/Q42918","display_name":"Mutation","level":3,"score":0.28949999809265137},{"id":"https://openalex.org/C112313634","wikidata":"https://www.wikidata.org/wiki/Q7886648","display_name":"Complement (music)","level":5,"score":0.2874999940395355},{"id":"https://openalex.org/C96232424","wikidata":"https://www.wikidata.org/wiki/Q4118072","display_name":"Cancer cell","level":3,"score":0.28690001368522644},{"id":"https://openalex.org/C12713177","wikidata":"https://www.wikidata.org/wiki/Q1900281","display_name":"Perspective (graphical)","level":2,"score":0.26969999074935913},{"id":"https://openalex.org/C14036430","wikidata":"https://www.wikidata.org/wiki/Q3736076","display_name":"Function (biology)","level":2,"score":0.26409998536109924},{"id":"https://openalex.org/C55105296","wikidata":"https://www.wikidata.org/wiki/Q841382","display_name":"Interaction network","level":3,"score":0.2524000108242035},{"id":"https://openalex.org/C144292202","wikidata":"https://www.wikidata.org/wiki/Q898273","display_name":"Protein domain","level":3,"score":0.25130000710487366}],"mesh":[],"locations_count":3,"locations":[{"id":"doi:10.5281/zenodo.7358736","doi":"https://doi.org/10.5281/zenodo.7358736","is_oa":true,"landing_page_url":"https://doi.org/10.5281/zenodo.7358736","pdf_url":null,"source":{"id":"https://openalex.org/S4306400562","display_name":"Zenodo (CERN European Organization for Nuclear Research)","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I67311998","host_organization_name":"European Organization for Nuclear Research","host_organization_lineage":["https://openalex.org/I67311998"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":null,"is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"JournalArticle"},{"id":"doi:10.5281/zenodo.7358737","doi":"https://doi.org/10.5281/zenodo.7358737","is_oa":true,"landing_page_url":"https://doi.org/10.5281/zenodo.7358737","pdf_url":null,"source":{"id":"https://openalex.org/S4306400562","display_name":"Zenodo (CERN European Organization for Nuclear Research)","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I67311998","host_organization_name":"European Organization for Nuclear Research","host_organization_lineage":["https://openalex.org/I67311998"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":null,"is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"JournalArticle"},{"id":"doi:10.5281/zenodo.7401670","doi":"https://doi.org/10.5281/zenodo.7401670","is_oa":true,"landing_page_url":"https://doi.org/10.5281/zenodo.7401670","pdf_url":null,"source":{"id":"https://openalex.org/S4306400562","display_name":"Zenodo (CERN European Organization for Nuclear Research)","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I67311998","host_organization_name":"European Organization for Nuclear Research","host_organization_lineage":["https://openalex.org/I67311998"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":null,"is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"JournalArticle"}],"best_oa_location":{"id":"doi:10.5281/zenodo.7358736","doi":"https://doi.org/10.5281/zenodo.7358736","is_oa":true,"landing_page_url":"https://doi.org/10.5281/zenodo.7358736","pdf_url":null,"source":{"id":"https://openalex.org/S4306400562","display_name":"Zenodo (CERN European Organization for Nuclear Research)","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I67311998","host_organization_name":"European Organization for Nuclear Research","host_organization_lineage":["https://openalex.org/I67311998"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":null,"is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"JournalArticle"},"sustainable_development_goals":[{"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3","score":0.6240000128746033}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W6920652380","https://openalex.org/W7149704258","https://openalex.org/W4323349878","https://openalex.org/W4306914612","https://openalex.org/W2331480251","https://openalex.org/W2133730856","https://openalex.org/W7169776434","https://openalex.org/W2186667705","https://openalex.org/W4285214844","https://openalex.org/W2529097733"],"abstract_inverted_index":{"Introduction":[0],"Considering":[1],"protein":[2,77],"mutations":[3,84,110,142],"in":[4,25,64,94,155,163,227],"their":[5,12],"biological":[6],"context":[7],"is":[8,221],"essential":[9],"for":[10,55,176,195,245],"understanding":[11],"functional":[13],"impact,":[14],"interpretation":[15],"of":[16,21,34,42,101,173,248],"high-dimensional":[17],"datasets":[18],"and":[19,59,71,76,92,165,233],"development":[20],"effective":[22],"targeted":[23],"therapies":[24],"personalized":[26],"medicine.":[27],"Methods":[28],"We":[29,81,98],"combined":[30],"the":[31,40,61,170],"curated":[32],"knowledge":[33],"biochemical":[35,231],"reactions":[36,72,91,232],"from":[37,46,69,85,223],"Reactome":[38],"with":[39,149],"analysis":[41,62,180],"interaction-mediating":[43],"3D":[44,78,217],"interfaces":[45],"Mechismo.":[47],"In":[48,201],"addition,":[49],"we":[50,139,203],"provided":[51],"a":[52,65,206],"software":[53],"tool":[54],"users":[56],"to":[57,73,113,118,209,237],"explore":[58],"browse":[60],"results":[63],"multi-scale":[66,207],"perspective":[67],"starting":[68],"pathways":[70,93,162],"protein-protein":[74,215],"interactions":[75],"structures.":[79,218],"Results":[80],"analyzed":[82],"somatic":[83],"TCGA,":[86],"revealing":[87],"several":[88,183],"significantly":[89,147],"impacted":[90],"specific":[95,156],"cancer":[96,115,157,167],"types.":[97],"found":[99,140],"examples":[100],"genes":[102],"not":[103],"yet":[104],"listed":[105],"as":[106],"oncodrivers,":[107,127],"whose":[108],"rare":[109],"were":[111],"predicted":[112],"affect":[114],"processes":[116,123,133,145,185],"similarly":[117],"known":[119,126],"oncodrivers.":[120],"Some":[121],"identified":[122],"lack":[124],"any":[125],"which":[128],"suggests":[129],"potentially":[130],"new":[131,196],"cancer-related":[132],"(e.g.":[134,159,186,241],"complement":[135],"cascade":[136],"reactions).":[137],"Furthermore,":[138],"that":[141],"perturbing":[143],"certain":[144],"are":[146],"associated":[148],"distinct":[150],"phenotypes":[151],"(i.e.":[152],"survival":[153],"time)":[154],"types":[158,240,247],"PIK3CA":[160],"centered":[161],"LGG":[164],"UCEC":[166],"types),":[168],"suggesting":[169],"translational":[171],"potential":[172],"our":[174],"approach":[175,208,220],"patient":[177],"stratification.":[178],"Our":[179,219],"also":[181],"uncovered":[182],"druggable":[184],"GPCR":[187],"signalling":[188],"pathways)":[189],"containing":[190],"enriched":[191],"reactions,":[192],"providing":[193],"support":[194],"off-label":[197],"therapeutic":[198],"options.":[199],"Conclusions":[200],"summary,":[202],"have":[204],"established":[205],"study":[210],"genetic":[211],"variants":[212],"based":[213],"on":[214,230],"interaction":[216],"different":[222],"previously":[224],"published":[225],"studies":[226],"its":[228],"focus":[229],"can":[234],"be":[235],"applied":[236],"other":[238],"data":[239],"post-translational":[242],"modifications)":[243],"collected":[244],"many":[246],"disease.":[249]},"counts_by_year":[{"year":2022,"cited_by_count":1},{"year":2021,"cited_by_count":1}],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2025-10-10T00:00:00"}