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PackageXINAJune82021TypePackageTitleMultiplexesIsobaricMassTaggedb PackageXINAJune82021TypePackageTitleMultiplexesIsobaricMassTaggedb

PackageXINAJune82021TypePackageTitleMultiplexesIsobaricMassTaggedb - PDF document

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PackageXINAJune82021TypePackageTitleMultiplexesIsobaricMassTaggedb - PPT Presentation

2RtopicsdocumentedPublicLicensealongwiththisprogramIfnotseegnuorxhttpxsxwww6倀glicensesContactemailsLLeeLHLEEBWHHARVARDEDUSSinghSASINGHBWHHARVARDEDUMAikawaMAIKAWABW ID: 839362

xina clusters condition plot clusters xina plot condition data result enrichment label size 149 color centrality clustering vertex null

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1 Package`XINA'June8,2021TypePackageTitleM
Package`XINA'June8,2021TypePackageTitleMultiplexesIsobaricMassTagged-basedKineticsDataforNetworkAnalysisVersion1.11.0biocViewsSystemsBiology,Proteomics,RNASeq,NetworkAuthorLangHoLee&#xlhle;@bw;&#xh.ha;&#xrvar; .ed;&#xu000;andSashaA.Singh&#xsasi;&#xngh@; wh.;&#xharv; rd.;íu0;MaintainerLangHoLee&#xlhle;@bw;&#xh.ha;&#xrvar; .ed;&#xu000;andSashaA.Singh&#xsasi;&#xngh@; wh.;&#xharv; rd.;íu0;DescriptionTheaimofXINAistodeterminewhichproteinsexhibitsimilarpatternswithinandacrossexperimentalconditions,sinceproteinswithco-abundancepatternsmayhavecommonmolecularfunctions.XINAimportsmultipledatasets,tagsdatasetinsilico,andcombinesthedataforsubsequentsubgroupingintomultipleclusters.Theresultisasingleoutputdepictingthevariationacrossallconditions.XINA,notonlyextractscoabundanceproleswithinandacrossexperiments,butalsoincorporatesprotein-proteininteractiondatabasesandintegrativeresourcessuchasKEGGtoinferinteractorsandmolecularfunctions,respectively,andproducesintuitivegraphicaloutputs.CopyrightXINAcombinesmultiplequantitative(kinetics)datasetsfromomicsstudiesintoasingleinputdatasetforclustering.Copyright(C)2018LangHoLee,Ard

2 aHalu,StephanieMorgan,HiroshiIwata,Masan
aHalu,StephanieMorgan,HiroshiIwata,MasanoriAikawa,andSashaA.SinghThisprogramisfreesoftware:youcanredistributeitand/ormodifyitunderthetermsoftheGNUGeneralPublicLicenseaspublishedbytheFreeSoftwareFoundation,eitherversion3oftheLicense,anylaterversion.Thisprogramisdistributedinthehopethatitwillbeuseful,butWITHOUTANYWARRANTY;withouteventheimpliedwarrantyofMERCHANTABILITYorFITNESSFORAPARTICULARPURPOSE.SeetheGNUGeneralPublicLicenseformoredetails.YoushouldhavereceivedacopyoftheGNUGeneral1 2Rtopicsdocumented:PublicLicensealongwiththisprogram.Ifnot,see.gnu.or&#xhttp;&#xs://;&#xwww6;倀g/licenses/.-Contactemails:L.Lee,LHLEE@BWH.HARVARD.EDUS.Singh,SASINGH@BWH.HARVARD.EDUM.Aikawa,MAIKAWA@BWH.HARVARD.EDU-Mailingaddress:DepartmentofMedicine,CardiovascularDivisionCenterforInterdisciplinaryCardiovascularSciences3BlackfanStreet,17thFloorBoston,MA02115USALicenseGPL-3Importsmclust,plyr,alluvial,ggplot2,igraph,gridExtra,tools,grDevices,graphics,utils,STRINGdbVignetteBuilderknitrLazyDataFALSERoxygenNote6.1.1EncodingUTF-8DependsR&#xhttp;&#xs://;&#xwww6;倀(=3.5)Suggestsknitr,rmarkdownDate2019-01-31git_urlhttps://git.bioconductor.org/packages/XINAgit_branchmastergit_l

3 ast_commit6b76fcfgit_last_commit_date202
ast_commit6b76fcfgit_last_commit_date2021-05-19Date/Publication2021-06-08Rtopicsdocumented:add_legend.........................................3alluvial_enriched......................................4alluvial_enrichment_tests..................................5calculate_centrality_scores.................................6default_size.........................................7draw_alluvial_plot.....................................7example_clusters......................................8extract_data_column....................................9nd_similar_clusters....................................9generate_count_table....................................10generate_superset......................................10get_colors..........................................11get_color_for_nodes....................................11get_comigrations_by_name.................................12get_condition_biased_comigrations............................13get_layout..........................................14get_mTOR_proteins....................................15get_random_data......................................15 add_legend3get_stats............................

4 ...............16get_theme_blank........
...............16get_theme_blank......................................16get_unknown_ppi_nodes..................................17gn..............................................17gn_desc...........................................18hprd_ppi...........................................18length2...........................................19load_previous_results....................................19make_random_xina_data..................................20mutate_colors........................................21organize_clusters......................................22plot_clusters.........................................22plot_clusters_all.......................................23plot_condition_compositions................................24plot_enrichment_results...................................25plot_NA...........................................26rank_centrality.......................................27string_example.......................................27xina_analysis........................................28xina_clustering.......................................29xina_enrichment......................................30xina_plot_all.....................

5 ...................32xina_plot_bycluster
...................32xina_plot_bycluster.....................................34xina_plot_single.......................................36xina_result_example....................................38Index40 add_legendadd_legend DescriptionAddplotlegendandlocateitoutsideofanetworkplotUsageadd_legend(legend_location="bottomright",...)Argumentslegend_locationNetworkcentralityscorematrix...Numeric,complex,orlogicalvectors.Valuealegendtoaplot 4alluvial_enriched alluvial_enrichedalluvial_enriched Description'alluvial_enriched'drawsanalluvialplotandndscomigratedproteins.Thecomigrationisagroupofproteinsthatshowthesameexpressionpattern,classiedandevaluatedbyXINAclustering,inatleasttwoconditions.XINAcanreducethedatasetcomplexitybylteringbasedonthenumberofcomigratedproteins(size,'comigration_size'parameter)andperformanenrichmenttest(P-valueofFisher'sexacttest,'pval_threshold')todeterminesignicanceofenrichedcomigrations.TheFisher'sexacttestcanonlybedonefortwoconditionsatatime.Thefollowing2x2tablewasusedtocalculatetheP-valuefromtheFisher'sexacttest.Toevaluatesignicanceofco-migratedproteinsfromcluster#1incontroltocluster#2intestgroup,-cluster#1

6 incontrolotherclustersincontrolcluster#2
incontrolotherclustersincontrolcluster#2intest65(TP)175(FP)otherclustersintest35(FN)979(TN)Usagealluvial_enriched(clustering_result,selected_conditions,comigration_size=0,pval_threshold=1,pval_method="fdr",cex=0.7,alpha=0.3)Argumentsclustering_resultAlistcontainingXINAclusteringresults.Seexina_clusteringselected_conditionsAvectorofconditionnamesusedinXINAclusteringresults.Thenumberofselectedconditionsshouldbeatleasttwo.comigration_sizeThenumberofproteinscomigratedtogetherintheselectedconditionsofXINAclusteringresults.Defaultis0pval_thresholdThisoptionisavaiableonlywhenyouselectedtwoconditionsforcomigrationsearch.pval_methodMethodforp-valueadjustment.Seep.adjustcexScalingoffontsofcategorylabels.Defaultif0.7.SeealluvialalphaTransparencyofthestripes.Defaultif0.3.SeealluvialValueAdataframecontainingcomigrationsandanalluvialplotshowingcomigrations alluvial_enrichment_tests5Examples#loadXINAexampledatadata(xina_example)#Gettheexperimentalconditionsintheexampledataclassesas.vector(example_clusters$condition)#Getcomigrationswithoutanythresholdsall_comigrationsalluvial_enriched(example_clusters,classes)#Getcomigrationsthathave&#x--50;�=5size(then

7 umberofcomigratedproteins)all_cor_enrich
umberofcomigratedproteins)all_cor_enrichedalluvial_enriched(example_clusters,classes,comigration_size=5)#GetallthecomigrationsbetweenControlandStimulus1comigrations_Control_Stimulus1alluvial_enriched(example_clusters,c(classes[1],classes[2]))#GetcomigrationsbetweenControlandStimulus1,thathave&#x--50;�=5sizecomigrations_Control_Stimulus1_over5alluvial_enriched(example_clusters,c(classes[1],classes[2]),comigration_size=5)#GetcomigrationsbetweenControlandStimulus1,#thathave&#x--50;�=5sizeandenrichmentFDR0.01comigrations_Control_Stimulus1_pval0.01_size5alluvial_enriched(example_clusters,c(classes[1],classes[2]),comigration_size=5,pval_threshold=0.01)#GetcomigrationsbetweenControlandStimulus1,#thathave&#x--50;�=5sizeandenrichmentBenjamini&Yekutieli0.01comigrations_Control_Stimulus1_BY0.01_size5alluvial_enriched(example_clusters,c(classes[1],classes[2]),comigration_size=5,pval_threshold=0.01,pval_method="BY") alluvial_enrichment_testsalluvial_enrichment_tests DescriptionFisher'sexacttesttocalculatethesignicanceoverallcomigrations.Thefollowing2x2tablewasusedtocalculatep-valuefromFisher'sexacttest.Toevaluatesignicanceofcomi

8 gratedproteinsfromcluster#1incontroltocl
gratedproteinsfromcluster#1incontroltocluster#2intestcondition,cluster#1incontrolotherclustersincontrolcluster#2intest65(TP)175(FP)otherclustersintest35(FN)979(TN)'alluvial_enrichment_tests'alsoprovidesanotherstatisticalmethodsincludingHypergeometrictest 6calculate_centrality_scoresandChi-squaretest.Usagealluvial_enrichment_tests(count_table,c1,c2,non_cluster=0,test_type="fisher")Argumentscount_tableAdataframegeneratedbyusingcount.c1Aselectedclusterintherstcondition.c2Aselectedclusterinthesecondcondition.non_clusterTheclusternumberforproteinsthatwerenotdetectedinaspecicsample.Defaultis0.test_typeEnrichmenttesttype.'sher'=Fisher'sexacttest,'hyper'=Hypergeometrictest,'chisq'=Chi-squaretestValueP-valueofcomigrationenrichmenttestand2x2tableinformation calculate_centrality_scorescalculate_centrality_scores Description'calculate_centrality_scores'computesnetworkcentralityscoresUsagecalculate_centrality_scores(net,centrality_type="Degree")Argumentsnetprotein-proteininteractionnetworkofigraphcentrality_typethemaximumnumberofclustersValueAvectorofnetworkcentralityscores default_size7 default_sizedefault_size DescriptionCalculateimagesizebase

9 donthenumberofclustersUsagedefault_size(
donthenumberofclustersUsagedefault_size(max_cluster)Argumentsmax_clusterthemaximumnumberofclustersValueAvectorofplotwidthandheight draw_alluvial_plotdraw_alluvial_plot Description'draw_alluvial_plot'drawaalluvialplotUsagedraw_alluvial_plot(clustering_result,selected_conditions,count_table,alluvia_colors=NULL,cex=0.7,alpha=0.3)Argumentsclustering_resultAlistcontainingXINAclusteringresults.Seexina_clustering.selected_conditionsAvectorofconditionnamesusedinXINAclusteringresults.Thenumberofselectedconditionsshouldbeatleasttwo.count_tableAdataframegeneratedbyusingcount.alluvia_colorsAvectorcontainingtheuser-denedcolorsforeachalluvium.cexSizeofclusternumberonblockaxis.Defaultif0.7.Seealluvial.alphaTransparencyofalluviacolors.Defaultis0.3.Seealluvial. 8example_clustersValueAnalluvialplotdisplayingcomigrationsandthedataframecontainingtheinputcount_tablewithcolors.Examples#loadXINAexampledatadata(xina_example)#getavectorofexperimentalconditionsanalyzedintheclusteringresultsclassesas.vector(example_clusters$condition)comigrations_size_over5alluvial_enriched(example_clusters,classes,comigration_size=5)draw_alluvial_plot(example_clusters,classes,comigr

10 ations_size_over5) example_clustersRando
ations_size_over5) example_clustersRandomlygeneratedexampledatasetsforXINAusers.Adatasetcon-tainingtheXINAclusteringresults. Description•aligned.XINAclusteringresultsalignedbyconditions•data_column.Columnnamesfordatamatrix•out_dir.Notavailableinthisexampledataset•nClusters.Thenumberofuser-desiredclusters.It's30intheexample.•max_cluster.Thenumberofclustersfoundinthedataset.It's21intheexample.•chosen_model.Thechosencovariancemodelfortheexampledataset.It'sVEIintheexample•optimal_BIC.BICattheoptimizedclustering.It's29473.57intheexample•condition.Theexperimentalconditionsinthedataset.•color_for_condition.ThedefaultcolorfortheconditionsthatwillbeusedinXINAplotdrawing.•color_for_clusters.ThedefaultcolorfortheclustersthatwillbeusedinXINAclusteringplot.•norm_method.Theusednormalizationmethodtostandardizetheinputdata.It's"sum_normalization"intheexample.FormatAlistwiththeexampleXINAclusteringresult extract_data_column9 extract_data_columnextract_data_column DescriptionExtractdatacolumnnamesfromXINAclusteringresultUsageextract_data_column(col_head_of_clustering)Argumentscol_head_of_clusteringColumnname

11 sofXINAclusteringresultValueAvectorconta
sofXINAclusteringresultValueAvectorcontainingcolumnnamesofdatamatrix find_similar_clustersnd_similar_clusters DescriptionCompareclustersandndsimilaronesUsagefind_similar_clusters(clustering_result,threshold=0.95)Argumentsclustering_resultAlistcontainingXINAclusteringresults.Seexina_clusteringthresholdPearson'srthresholdtondsimilaronesValueWriteacsvlecontainingsimilarclusteringinformationbasedonthegivenPearson'sRthreshold 10generate_superset generate_count_tablegenerate_count_table DescriptionCountthenumberofcomigratedproteinsusingcountUsagegenerate_count_table(clustering_result,selected_conditions,comigration_size)Argumentsclustering_resultAlistcontainingXINAclusteringresults.Seexina_clusteringselected_conditionsAvectorofconditionnamesusedinXINAclusteringresults.comigration_sizeThenumberofproteinscomigratedtogetherintheselectedconditionsofXINAclusteringresults.Defaultis0.ValueAdataframecontainingcomigrations. generate_supersetgenerate_superset DescriptionMergeinputkineticslesUsagegenerate_superset(f_names,data_column,delim=",",norm="sum_normalization")Argumentsf_namesAvectorof.csvlepathscontainingkineticsdatadata_columnA

12 vectorofcolumnnamescontainingdatamatrixd
vectorofcolumnnamescontainingdatamatrixdelimThedelimiterofinputle(defaultis',')normThenormalizationmethod.Itshouldbeoneofc('sum_normalization','zs-core').Defaultis'sum_normalization'. get_colors11ValueAdataframecontainingkineticsdataobtainedfromlesinthef_namesvector get_colorsget_colors DescriptionGeneratecolorseriesforXINAgraphicsUsageget_colors(nClusters,set="",colorset=NULL)ArgumentsnClustersThenumberofclusterssetPre-denedcolorseriessetcolorsetmanuallydenedcolorcodesValueAvectorforcolorcodeofXINAgraphics get_color_for_nodesget_color_for_nodes DescriptionPre-dened30colorsUsageget_color_for_nodes()ValueAvectorforcolorcodeofXINAgraphics 12get_comigrations_by_name get_comigrations_by_nameget_comigrations_by_name Description'get_comigrations_by_name'ndsproteinscomigratedwiththegivenproteinsUsageget_comigrations_by_name(clustering_result,selected_conditions,protein_list,cex=0.7,alpha=0.3)Argumentsclustering_resultAlistcontainingXINAclusteringresults.Seexina_clusteringselected_conditionsAvectorofconditionnamesusedinXINAclusteringresults.Thenumberofselectedconditionsshouldbeatleasttwo.protein_listAvectorcontaininggenenames.ce

13 xSizeofclusternumberonblockaxis.Defaulti
xSizeofclusternumberonblockaxis.Defaultif0.7.SeealluvialalphaTransparencyofalluviacolors.Defaultis0.3.SeealluvialValueAnalluvialplotdisplayingcomigrationsandthedataframecontainingcomigrationsoftheinputproteinsExamples#loadXINAexampledatadata(xina_example)#theclusteringresulttableall_proteinsas.character(example_clusters$aligned$`Genename`)#getavectorofexperimentalconditionsanalyzedintheclusteringresultsclassesas.vector(example_clusters$condition)comigrated_prots_allget_comigrations_by_name(example_clusters,classes,all_proteins[1:3]) get_condition_biased_comigrations13 get_condition_biased_comigrationsget_condition_biased_comigrations Descriptiongetcomigrationsthatatleastonebiasedclusterisinvolvedin.BiasedclustersaredenedbyUsageget_condition_biased_comigrations(clustering_result,count_table=NULL,selected_conditions,condition_composition,threshold_percent=50,color_for_null="gray",color_for_highly_matched="red4",cex=0.7,alpha=0.3)Argumentsclustering_resultAlistcontainingXINAclusteringresults.Seexina_clusteringcount_tableAdataframegeneratedbyusingcount.Ifcount_tableisNULL(bydefault),XINAwillconsiderallthecomigrations.selected_conditionsAvectoro

14 fconditionnamesusedinXINAclusteringresul
fconditionnamesusedinXINAclusteringresults.Thenumberofselectedconditionsshouldbeatleasttwo.condition_compositionTheresultingdataframeof'plot_condition_compositions'.Seeplot_condition_compositions.threshold_percentDefaultis50.Thepercentagethresholdforndingcondition-biasedclusterscolor_for_nullAcolorfornon-condition-biasedcomigrations.Defaultis'gray'color_for_highly_matchedAcolorforcomigrationsthatareinvolvedwithmorethantwocondition-biasedclusters.Defaultis'red4'cexSizeofclusternumberonblockaxis.Defaultif0.7.Seealluvial.alphaTransparencyofalluviacolors.Defaultis0.3.Seealluvial.ValueAnalluvialplotdisplayingcomigrationsandthedataframecontainingcondition-biasedcomigra-tions.Examples#loadXINAexampledatadata(xina_example)#getavectorofexperimentalconditionsanalyzedintheclusteringresults 14get_layoutconditionsas.vector(example_clusters$condition)#getconditioncompositioninformationcondition_compositionplot_condition_compositions(example_clusters)comigrations_size10alluvial_enriched(example_clusters,conditions,comigration_size=10)#Findingcondition-biasedcomigrationsby50%thresholdcondition_biased_comigrationsget_condition_biased_comigrations(clustering

15 _result=example_clusters,count_table=com
_result=example_clusters,count_table=comigrations_size10,selected_conditions=conditions,condition_composition=condition_composition)#Findingcondition-biasedcomigrationsby70%thresholdcondition_biased_comigrationsget_condition_biased_comigrations(clustering_result=example_clusters,count_table=comigrations_size10,selected_conditions=conditions,condition_composition=condition_composition,threshold_percent=70) get_layoutget_layout DescriptionGetigraphlayoutbythenumberofnodesUsageget_layout(subnet_condition)Argumentssubnet_conditionAigraphsub-networkValueigraphnetworklayout get_mTOR_proteins15 get_mTOR_proteinsget_mTOR_proteins DescriptionGetmTORpathwaygenesUsageget_mTOR_proteins(time_points,conditions)Argumentstime_pointsAvectorcontainingtimepointsofthedatamatrixconditionsAvectorcontainingconditioninformation,forexamplenormal,diseaseanddrugtreateddisase.ValueAvectorcontainingmTORpathwaygenenames get_random_dataget_random_data DescriptionGetrandomizedtime-seriesdataUsageget_random_data(time_points,conditions,num_total,percent.sign=0.1,equal=TRUE)Argumentstime_pointsAvectorcontainingtimepointsofthedatamatrixconditionsAvectorcontainingconditioninformat

16 ion,forexamplenormal,diseaseanddrugtreat
ion,forexamplenormal,diseaseanddrugtreateddisase.num_totalThenumberoftotalproteinstobegeneratedpercent.signPercentageofdifferentiallyexpressedproteins.Ignoredwhenequal=FALSE.equalIfequalisTRUE,alltheconditionswillhavenumbersbetween0and1.IfitisFALSE,therstthreeconditionswillhavedifferentranges.Firstconditionwillhavenumbersfrom0.3to0.4.Secondconditionwillhavenumbersfrom0.6to0.8.Thirdconditionwillhavenumbersfrom0.3to0.5.Otherconditionswillhavenumbersfrom0to1. 16get_theme_blankValueAlistcontainingramdomlygenerateddatamatrix get_statsget_stats DescriptionCalculatestatisticsofthegivendataforXINAnetworkanalysisUsageget_stats(centrality_results,na.rm=FALSE)Argumentscentrality_resultsNetworkcentralityscoredataframecalculatedbyXINAnetworkmodulena.rmIfitisFALSE,noexclusionofNAvalues.ValueAdataframecontainingstatisticsofXINAnetworkcentralityscores get_theme_blankget_theme_blank DescriptionPredenedggplotthemeforremovingticks,titlesandlabelsofXandYaxisUsageget_theme_blank()ValueAggplottheme get_unknown_ppi_nodes17 get_unknown_ppi_nodesget_unknown_ppi_nodes DescriptionGetproteinswithnoknowninteractionswithintheclusterbasedontheusedprotein-proteininter

17 -actiondatabasesourceUsageget_unknown_pp
-actiondatabasesourceUsageget_unknown_ppi_nodes(xina_result,cl)Argumentsxina_resultAlistcontainingXINAnetworkanalysisresults.Seexina_analysiscltheclusteringnumberofXINAclusteringresults.Seexina_clusteringValueAdataframecontainingproteinswithnoknowninteractionswithintheclusterbasedontheusedprotein-proteininteractiondatabasesourceExamples#loadXINAexampledatadata(xina_example)#loadthepreviouslyprocessedXINAanalysisresults#ifyouwanttolearnhowtorun'xina_analysis',pleasesee\link[XINA]{xina_analysis}data(xina_result_example)#ExtractunknownPPInodesinthecluster#1get_unknown_ppi_nodes(xina_result_example,1) gnAcharactervectorcontaining19,396humangenesThisisfortheran-domedatagenerationofXINA Description•CharactersofhumangenesFormatAcharactervectorcontaining19,396humangenes 18hprd_ppiSourcehttps://www.ncbi.nlm.nih.gov/gene gn_descAcharactervectorcontaining19,396humangenedescriptionsThisisfortherandomedatagenerationofXINA Description•Humangenedescriptioncorrespondingto'gn'vectorFormatAcharactervectorcontaining19,396humangenedescriptionsSourcehttps://www.ncbi.nlm.nih.gov/gene hprd_ppiProtein-proteininteractionresourcedownloadedfromHPRDDBAdataframec

18 ontainingHRPDprotein-proteininteractiond
ontainingHRPDprotein-proteininteractiondata Description•gene_symbol_1.Genenameinteractingwithgenenamein'gene_symbol_2'•gene_symbol_2.Genenameinteractingwithgenenamein'gene_symbol_1'•Experiment_type.ExperimentalorcomputationalmethodssupportingtheinteractionFormatAdataframecontainingHRPDprotein-proteininteractiondataSourcehttp://www.hprd.org/ length219 length2length2 DescriptionCustomizedfunctionforvectorlengthcalculationUsagelength2(x,na.rm=FALSE)ArgumentsxAvectorna.rmIfitisFALSE,noexclusionofNAvalues.ValueAvectorlength load_previous_resultsload_previous_results DescriptionGetpreviousXINAclusteringresultstoRspaceUsageload_previous_results(clustering_dir=getwd(),data_column=NULL,fp_clusters="xina_clusters.csv")Argumentsclustering_dirThedirectorypathofXINAclusteringresultsdata_columnAvectorcontainingcolumnnamesofdatamatrixfp_clustersFilepathofXINAclusteringresultsValueComma-separatedlecontainingalignedXINAclusteringresults. 20make_random_xina_dataExamples#LoadXINA'sexampledatadata(xina_example)write.csv(example_clusters$aligned,"xina_clusters_aligned.csv")write.csv(example_clusters$clusters,"xina_clusters.csv")#Reloadtheclusteri

19 ngresultexample_clusters_reloadedload_pr
ngresultexample_clusters_reloadedload_previous_results(".") make_random_xina_datamake_random_xina_data DescriptionGeneraterandomproteomicsdatasetfortestingXINA'make_random_xina_data'willmakeran-domproteomicsdataforXINAtest.Thegenerateddatawillhavethreeconditionsandseventimepoints,c("0hr","2hr","6hr","12hr","24hr","48hr","72hr").Usagemake_random_xina_data(n=500,mtor=TRUE,time_points=c("0hr","2hr","6hr","12hr","24hr","48hr","72hr"),conditions=c("Control","Stimulus1","Stimulus2"))ArgumentsnThenumberofproteinsforonecondition.Defaultis500.mtorIfitisTRUE(default),mTORpathwaygeneswillbesignicant.IfitisFALSE,randomlyselectedgeneswillbesignicantinrstthreeconditions.time_pointsAvectorcontainingtimepointsofthedatamatrixconditionsAvectorcontainingconditioninformation,forexamplenormal,diseaseanddrugtreateddisase.ValueThreecomma-separatedlescontainingtime-seriesdataforXINAExamplesmake_random_xina_data()g1read.csv("Control.csv",check.names=FALSE,stringsAsFactors=FALSE)g2read.csv("Stimulus1.csv",check.names=FALSE,stringsAsFactors=FALSE)g3read.csv("Stimulus2.csv",check.names=FALSE,stringsAsFactors=FALSE) mutate_colors21head(g1)head(g2)head(g3) m

20 utate_colorsmutate_colors Description'mu
utate_colorsmutate_colors Description'mutate_colors'generatesnewcolorschemeforXINAclusteringplotbasedonconditioncomposi-tionresults(plot_condition_compositions).Ifanyclustershavehigherpercentagethanthe'thresh-old_percent',XINAwillassignnewcolorsinaccordanceto'color_for_condition'.Ifnot,XINAwillgive'gray'colororuser-denedcolorvia'null_color'parameter.Usagemutate_colors(condition_composition,color_for_condition,null_color="gray",threshold_percent=50)Argumentscondition_compositionAdataframegeneratedbyplot_condition_compositionscolor_for_conditionAvectorlike'color_for_condition'ofxina_clusteringnull_colorDefaultis'gray'.Thiscolorisforclustersthatarenotbiasedtoanyofexperi-mentalconditionsthreshold_percentDefaultis50.ThepercentagethresholdforgivingnewcolorsValueAdataframecontainingstatisticsofXINAnetworkcentralityscoresExamples#loadXINAexampledatadata(xina_example)#Plotconditioncompositionpie-chartwithdefaultoptioncondition_compositionplot_condition_compositions(example_clusters)example_clusters$color_for_clustersmutate_colors(condition_composition,example_clusters$color_for_condition)plot_clusters(example_clusters,xval=c(0,2,6,12,24,48,72),xylab

21 =FALSE) 22plot_clusters organize_cluster
=FALSE) 22plot_clusters organize_clustersorganize_clusters DescriptionOrganizeXINAclusteringinformationbygenenameUsageorganize_clusters(clustering_dir=getwd(),super_ds,file_out=TRUE)Argumentsclustering_dirThedirectorypathofXINAclusteringresultssuper_dsXINAclustersfile_outIfitisTRUE,itwritesthealignedclusteringinformaionto"xina_clusters_aligned.csv"le.ValueComma-separatedlecontainingalignedXINAclusteringresults. plot_clustersplot_clusters DescriptionDrawalltheclusteringresults.'plot_clusters'drawstwoplots,scaledandunscaledlinegraphs.Scaledgraphshavesameylimitsthatare0to1bydefault,butcanbechangedvia'y_lim'parameter.Usageplot_clusters(clustering_result,y_lim=NULL,xval=NULL,xtickmark=NULL,xylab=TRUE,ggplot_theme=NULL)Argumentsclustering_resultAlistcontainingXINAclusteringresults.Seexina_clusteringy_limYaxislimit.Ifyousety_lim=c(0,1),'plot_clusters'willplotlinegraphsscaledfrom0to1iny-axisDefaultisNULL,whichmeansunscaledlinegraphs.xvalXINAbasicallyconsiderstimepointsasaordinaryvariable,like1,2,3,4...n.Youcanmakethetimepointsasacontinuousvariableusingxval.xtickmarkChangeXaxistickmarks.Defaultisdata_columnoftheclusteringresultlist.xylabIfitisFA

22 LSE,xandylabelswillbeblank.IfitisTRUE(de
LSE,xandylabelswillbeblank.IfitisTRUE(defualt),xandylabelswillbeshown.ggplot_themeThisisggplotthemetomodifyXINAclusteringplot. plot_clusters_all23ValueLinegraphsofalltheclustersExampleslibrary(ggplot2)#loadXINAexampledatadata(xina_example)#Drawclusteringplotsplot_clusters(example_clusters)#Applythemetotheclusteringplottheme1theme(title=element_text(size=8,face='bold'),axis.text.x=element_text(size=7),axis.text.y=element_blank(),axis.ticks.x=element_blank(),axis.ticks.y=element_blank(),axis.title.x=element_blank(),axis.title.y=element_blank())plot_clusters(example_clusters,ggplot_theme=theme1) plot_clusters_allplot_clusters_all DescriptionDrawlinegraphsofalltheproteinsinthegivendatasetUsageplot_clusters_all(clustering_result,selected_condition=NULL)Argumentsclustering_resultAlistcontainingXINAclusteringresults.Seexina_clusteringselected_conditionAconditionnametodrawthekineticsplotValuealistcontainingclusteringresultsandpdflecontainingaBICplotincurrentworkingdirectory. 24plot_condition_compositionsExamples#loadXINAexampledatadata(xina_example)#PlotkineticsofalltheproteinsinControlplot_clusters_all(example_clusters,selected_condition="Control"

23 )#PlotkineticsofalltheproteinsinStimulus
)#PlotkineticsofalltheproteinsinStimulus1plot_clusters_all(example_clusters,selected_condition="Stimulus1")#PlotkineticsofalltheproteinsinStimulus2plot_clusters_all(example_clusters,selected_condition="Stimulus2")#Plotkineticsofalltheproteinsinthreedataplot_clusters_all(example_clusters) plot_condition_compositionsplot_condition_compositions DescriptioncomputesconditioncompositionoftheXINAclusteringresultsanddrawspie-charts.Usageplot_condition_compositions(clustering_result,bullseye=FALSE,ggplot_theme=NULL)Argumentsclustering_resultAlistcontainingXINAclusteringresults.Seexina_clusteringbullseyeIfitisTRUE,drawbullseyeplotinsteadofthepie-chart.DefaultisFALSEggplot_themeThisisggplotthemetomodifyconditioncompositionpie-chartandbulleseyeplots.ValueAconditioncompositionplotandadataframecontainingconditioncompositionsoftheclusters plot_enrichment_results25Examples#loadXINAexampledatadata(xina_example)#Plotconditioncompositionpie-chartwithdefaultoptionplot_condition_compositions(example_clusters)#Makeanewcolorcodeforconditionscondition_colorsc("tomato","steelblue1","gold")names(condition_colors)example_clusters$conditionexample_clusters$color_for_condi

24 tioncondition_colors#Drawconditioncompos
tioncondition_colors#Drawconditioncompositionpie-chartwiththenewcolorcodeplot_condition_compositions(example_clusters)#Drawconditioncompositionbullseyeplotplot_condition_compositions(example_clusters,bullseye=TRUE) plot_enrichment_resultsplot_enrichment_results DescriptionPlotGOandKEGGenrichmentresultsUsageplot_enrichment_results(enriched_results,term_description="term_description",sig_score="pvalue",num_terms=0,get_log=TRUE,fill_color="darkgray")Argumentsenriched_resultsGOorKEGGenrichmentresults.Seexina_enrichmentandxina_enrichmentterm_descriptionDescriptionoftermstobedrawnonYaxis.Defaultis"term_description"ofXINAenrichmentresults.sig_scoresignicantscoretoplotonXaxis.Defaultis"pvalue".num_termsThenumberoftermstobeplotted.Defaultis0,whichmenasnolimit.get_logIfthisisTRUE,'plot_enrichment_results'willtake-log10ofp-values.fill_colorDefaultis'darkgray'.Youcanchangecolorofbars.Valueggplotbargraph 26plot_NAExamples##Notrun:library(STRINGdb)#loadXINAexampledatadata(xina_example)#GetSTRINGdatabaseforprotein-proteinintereactioninformationstring_dbSTRINGdb$new(version="10",species=9606,score_threshold=0,input_directory="")string_db#XINAanalysiswithST

25 RINGDBxina_resultxina_analysis(example_c
RINGDBxina_resultxina_analysis(example_clusters,string_db)#Selectproteinsthatshowedcluster#1intheStimulus2conditionsubgroupsubset(example_clusters$aligned,Stimulus2==1)protein_listas.vector(subgroup$`Genename`)#Enrichmenttestandgetsignificantlyenrichedfunctionalterms#thathaveadjusetedp-valuelessthan0.1kegg_enrichedxina_enrichment(string_db,protein_list,enrichment_type="KEGG",pval_threshold=0.1)plot_enrichment_results(kegg_enriched$KEGG,num_terms=10)##End(Notrun) plot_NAplot_NA DescriptionDrawNULLplotUsageplot_NA()Valueaemptyplot rank_centrality27 rank_centralityrank_centrality DescriptionGiveranksbasedonnetworkcentralityscoresUsagerank_centrality(centrality_score,type,num_breaks=5)Argumentscentrality_scoreNetworkcentralityscorematrixtypeNetworkcentralityscoretype,suchas'Eigenvector'num_breaksThenumberofranksValueAvectorcontainingranks string_exampleProtein-proteininteractionresourcedownloadedfromSTRINGDBforXINA'sexampledatasetAdataframecontainingprotein-proteininter-actions Description•gene_symbol_1.Genenameinteractingwithgenenamein'gene_symbol_2'•gene_symbol_2.Genenameinteractingwithgenenamein'gene_symbol_1'•PPI_Source.Dataorigi

26 nalsourceFormatAdataframecontainingSTRIN
nalsourceFormatAdataframecontainingSTRINGprotein-proteininteractiondataSourcehttps://string-db.org/ 28xina_analysis xina_analysisxina_analysis Descriptionxina_analysisistoanalyzeprotein-proteininteraction(PPI)networksusingSTRINGdbandigraphRpackage.ThismodulecomputesPPInetworkswithineachXINAclusters.Usagexina_analysis(clustering_result,ppi_db,is_stringdb=TRUE,flag_simplify=TRUE,node_shape="sphere",num_clusters_in_row=5,img_size=NULL,img_qual=300)Argumentsclustering_resultAlistcontainingXINAclusteringresults.Seexina_clusteringppi_dbSTRINGdbobjectis_stringdbIfitisTRUE(default),XINAwillprocess'ppi_db'asSTRINGdb,butitisFALSE,XINAwillacceptsyour'ppi_db'asitis.YoucanmakeyourownigraphnetworkusingcustomizedPPIinformationinsteadofSTRINGdb.flag_simplifyIfitisTRUE(default),XINAwillexcludeunconnectedproteinsnode_shapeYoucanchoosenodeshape.Defaultis"sphere".Seeshapesnum_clusters_in_rowThenumberofclustersinarowontheXINAnetworkplot.Defaultis5.img_sizeSettheimagesize.Forwidth=1000andheight=1500,itisimg_size=c(1000,1500).img_qualSettheimageresolution.Defaultis300.ValueAPNGle(XINA_Cluster_Networks.png)displayingPPInetworkplotsofalltheclustersandalistcontainin

27 gXINAnetworkanalysisresults.ItemDescript
gXINAnetworkanalysisresults.ItemDescriptionAll_networkPPInetworkofalltheinputproteinsSub_networkAlistcontainingPPInetworksofeachclustersDataXINAclusteringresults.Seexina_clusteringNodesAlistofproteinsineachclusterConditionsAlistofexperimentalconditionofproteinsineachclusterTitlesAlistofplottitlesforXINAplottingout_dirAdirectorypathstoringXINAnetworkanalysisresultsis_stringdbFalse=differentPPIDBandTRUE=STRINGDB xina_clustering29Examples##Notrun:#loadXINAexampledatadata(xina_example)#usethefollowingcodeforutilizingup-to-dateSTRINGDBtax_id9606#forhuman#tax_id10090#formouselibrary(STRINGdb)library(igraph)string_dbSTRINGdb$new(version='10',species=tax_id,score_threshold=0,input_directory='')string_dbxina_resultxina_analysis(example_clusters,string_db,flag_simplify=FALSE)#RunXINAwithaprotein-proteininteractionedgelistdata(HPRD)net_allsimplify(graph_from_data_frame(d=hprd_ppi,directed=FALSE),remove.multiple=FALSE,remove.loops=TRUE)xina_resultxina_analysis(example_clusters,net_all,is_stringdb=FALSE,flag_simplify=FALSE)##End(Notrun) xina_clusteringxina_clustering DescriptionClusteringmultiplexedtime-seriesomicsdatatondco-abundanceprolesUsagexina

28 _clustering(f_names,data_column,out_dir=
_clustering(f_names,data_column,out_dir=getwd(),nClusters=20,norm="sum_normalization",chosen_model="")Argumentsf_namesAvectorcontaininginputle(.csv)pathsdata_columnAvectorcontainingcolumnnames(1strowoftheinputle)ofdatamatrixout_dirAdirectorypathforsavingclusteringresults.(default:out_dir=getwd())nClustersThenumberofdesiredmaximumclustersnormDefaultis"sum_normalization".Sum-normalizationistodividethedatama-trixbyrowsum.Ifyouwanttoknowmoreaboutsum-normalization,seehttps://www.ncbi.nlm.nih.gov/pubmed/19861354."zscore"istocalculateZscoreforeachprotein.Seescale.chosen_modelYoucanchooseaspecicmodelratherthantestingallthemodelsthatareavail-ableinmclust.mclustModelNamesIfyouwantk-meansclusteringinsteadofthemodel-basedclustering,use"kmeans"here. 30xina_enrichmentValueaplotcontainingaBICplotincurrentworkingdirectoryandalistcontainingbelowinformation:ItemDescriptionclustersXINAclusteringresultsalignedXINAclusteringresultsalignedbyIDdata_columnDatamatrixcolumnnamesout_dirThedirectorypathcontainingXINAresultsnClustersThenumberofclustersdesiredbyusermax_clusterThenumberofclustersoptimizedbyBICchosen_modelTheusedcovariancemodelformodel-basedcluste

29 ringoptimal_BICBICoftheoptimizedcovarian
ringoptimal_BICBICoftheoptimizedcovariancemodelconditionExperimentalconditionsoftheuserinputdatacolor_for_conditionColorsassignedtoeachexperimentalconditionswhichisusedforconditioncompositionplotcolor_for_clustersColorsassignedtoeachclusterswhichisusedforXINAclusteringplotnorm_methodUsednormalizationmethodExamples#Generaterandommultiplexedtime-seriesdatarandom_data_infomake_random_xina_data()#Datafilesdata_filespaste(random_data_info$conditions,".csv",sep='')#timepointsofthedatamatrixdata_columnrandom_data_info$time_points#mclustrequiresthefixedrandomseedtogetreproducetheclusteringresultsset.seed(0)#Runthemodel-basedclusteringtofindco-abundanceprofilesexample_clustersxina_clustering(data_files,data_column=data_column,nClusters=30)#Runk-meansclusteringtofindco-abundanceprofilesexample_clustersxina_clustering(data_files,data_column=data_column,nClusters=30,chosen_model="kmeans") xina_enrichmentxina_enrichment Descriptionxina_enrichmentconductsfunctionalenrichmenttestsusinggeneontologyorKEGGpathwaytermsforagivenproteinlist xina_enrichment31Usagexina_enrichment(string_db,protein_list,enrichment_type="GO",pval_threshold=0.05,methodMT="fdr")Arguments

30 string_dbSTRINGdbobjectprotein_listAvect
string_dbSTRINGdbobjectprotein_listAvectorofgenenamestodrawprotein-proteininteractionnetwork.enrichment_typeAfunctionalannotationfortheenrichmenttest.'enrichment_type'shouldbeoneof'GO'and'KEGG',pval_thresholdP-valuethresholdtogetsignicantlyenrichedtermsfromthegivenproteinsmethodMTMethodforp-valueadjustment.Seeget_enrichment.Defaultis'fdr'.ValueAlistofdataframescontainingenrichmentresultsExamples##Notrun:library(STRINGdb)library(Biobase)#loadXINAexampledatadata(xina_example)#GetSTRINGdatabaseforprotein-proteinintereactioninformationstring_dbSTRINGdb$new(version="10",species=9606,score_threshold=0,input_directory="")string_db#XINAanalysiswithSTRINGDBxina_resultxina_analysis(example_clusters,string_db)#Selectproteinsthatshowedcluster#1intheStimulus2conditionsubgroupsubset(example_clusters$aligned,Stimulus2==1)protein_listas.vector(subgroup$`Genename`)#EnrichmenttestusingKEGGpathwaytermsthathaveadjusetedp-valuelessthan0.1kegg_enrichedxina_enrichment(string_db,protein_list,enrichment_type="KEGG",pval_threshold=0.1)plot_enrichment_results(kegg_enriched$KEGG,num_terms=10)#EnrichmenttestusingGOtermsthathaveadjusetedp-valuelessthan0.1go_enrichedxina

31 _enrichment(string_db,protein_list,enric
_enrichment(string_db,protein_list,enrichment_type="GO",pval_threshold=0.1)plot_enrichment_results(go_enriched$Component,num_terms=10)##End(Notrun) 32xina_plot_all xina_plot_allxina_plot_all Descriptionxina_plot_allistodrawprotein-proteininteractionnetworkplotsofalltheclustersUsagexina_plot_all(xina_result,clustering_result,condition="all",centrality_type=NULL,flag_simplify=TRUE,num_breaks=5,layout_specified="",vertex_label_flag=FALSE,vertex.label.color="black",vertex.color="",edge.color=NULL,vertex.label.dist=0.6,vertex.label.cex=0.8,edge.arrow.size=0.4,vertex.size=10,vertex.shape="sphere",legend_location="bottom",num_clusters_in_row=5,flag_unknown_only=FALSE,img_size=NULL,img_qual=300)Argumentsxina_resultAlistcontainingXINAnetworkanalysisresults.Seexina_analysisclustering_resultAlistcontainingXINAclusteringresults.Seexina_clusteringconditionDefaultis'all',whichmeansusealltheproteinstodrawgraphs.IfyouspecifytheexperimentalconditionnameusedforXINAclustering,xina_plot_allwilldrawgraphsusingspeciccondition'sproteins.centrality_type'centrality_type'shouldbeoneofc('Degree','Eigenvector','Hub','Author-ity','Closeness','Betweenness')Centralitysco

32 reigraphfunctionDegreedegreeEigenvectore
reigraphfunctionDegreedegreeEigenvectoreigen_centralityHubhub_scoreAuthorityauthority_scoreClosenessclosenessBetweennessbetweennessflag_simplifyIfitisTRUE(default),XINAwillexcludeunconnectedproteinsnum_breaks'num_breaks'isthenumberofranksbasedonnetworkcentrality.Defaultis5.layout_specifiedThiscanchangenetworklayout.'layout_specied'shouldbeoneofc('sphere','star','gem','tree','circle','random','nicely').XINA'slayoutsarebasedonigraph'slayout.Seelayout_ xina_plot_all33Layoutigraphlayoutnamespherelayout_on_spherestarlayout_as_stargemlayout_with_gemtreelayout_as_treecirclelayout_in_circlerandomlayout_randomlynicelylayout_nicelyDefaultis'layout_nicely'ofigraphvertex_label_flagIfvertex_label_agisTRUE(default),igraphnetworkgraphswillbelabeledbygenenamesIfvertex_label_agisFALSE,igraphnetworkgraphswillbedrawnwithoutlabelsvertex.label.colorColoroflabels.Defaultisblackvertex.colorColorofnodes.Defaultispink.edge.colorColorofedges.Defaultispink.vertex.label.distDistancebetweennodeandlabel.Defaultis0.6vertex.label.cexSizeoflabelsDefaultis0.8edge.arrow.sizeSizeofedgesDefaultis0.4vertex.sizeSizeofnodesDefaultis10vertex.shapeYoucanchoosenodeshape.Defa

33 ultis'sphere'.Seeshapeslegend_locationIf
ultis'sphere'.Seeshapeslegend_locationIfcentrality_typeischosen,xina_plot_singleaddthecolorlegendguidingrankofnodesbasedonthecentralityscore.Defaultis'bottomright',butyoucanchooseoneofthese'bottomright','bottom','bottomleft','left','topleft','top','topright','right'and'center'.num_clusters_in_rowThenumberofclustersinarowontheXINAnetworkplot.Defaultis5.flag_unknown_onlyIfthisisTRUE,'xina_plot_all'willplotproteinsthatdonothaveanyprotein-proteininteractioninthegivendatabaseimg_sizeSettheimagesize.Forwidth=1000andheight=1500,itisimg_size=c(1000,1500).Defaultisc(3000,3000)img_qualSettheimageresolution.Defaultis300.ValuePNGimagesofPPInetworkplotsofalltheclusters 34xina_plot_byclusterExamples##thefollowingcodeistoshowhowitworksquickly##loadXINAexampledatadata(xina_example)##loadthepreviouslyprocessedXINAanalysisresults#ifyouwanttolearnhowtorun'xina_analysis',pleasesee\link[XINA]{xina_analysis}data(xina_result_example)#XINAnetworkplotsxina_plot_all(xina_result_example,example_clusters)#XINAnetworkplotsforControlconditionxina_plot_all(xina_result_example,example_clusters,condition='Control') xina_plot_byclusterxina_plot_bycluster Descriptionxina_plot_by

34 clusteristodrawprotein-proteininteractio
clusteristodrawprotein-proteininteractionnetworkplotsofeachclusterUsagexina_plot_bycluster(xina_result,clustering_result,cl=NULL,condition="all",flag_legend=TRUE,centrality_type=NULL,flag_simplify=TRUE,layout_specified="",vertex_label_flag=TRUE,vertex.label.dist=0.6,vertex.label.cex=0.8,edge.arrow.size=0.4,vertex.size=10,vertex.shape="sphere",vertex.color="",edge.color="darkgray",legend_location="bottom",flag_unknown_only=FALSE)Argumentsxina_resultAlistcontainingXINAnetworkanalysisresults.Seexina_analysisclustering_resultAlistcontainingXINAclusteringresults.Seexina_clusteringclClusternumberintheXINAclusteringresultsconditionDefaultis'all',whichmeansusealltheproteinstodrawgraphs.IfyouspecifytheexperimentalconditionnameusedforXINAclustering,flag_legendIfitisTRUE,alegendwillbeprintedouttogether.centrality_type'centrality_type'shouldbeoneofc('Degree','Eigenvector','Hub','Author-ity','Closeness','Betweenness') xina_plot_bycluster35CentralityscoreigraphfunctionDegreedegreeEigenvectoreigen_centralityHubhub_scoreAuthorityauthority_scoreClosenessclosenessBetweennessbetweennessflag_simplifyIfitisTRUE(default),XINAwillexcludeunconnectedproteinslayout_spec

35 ifiedThiscanchangenetworklayout.'layout_
ifiedThiscanchangenetworklayout.'layout_specied'shouldbeoneofc('sphere','star','gem','tree','circle','random','nicely').XINA'slayoutsarebasedonigraph'slayout.Seelayout_Layoutigraphlayoutnamespherelayout_on_spherestarlayout_as_stargemlayout_with_gemtreelayout_as_treecirclelayout_in_circlerandomlayout_randomlynicelylayout_nicelyDefaultis'layout_nicely'ofigraphvertex_label_flagIfvertex_label_agisTRUE(default),igraphnetworkgraphswillbelabeledbygenenamesIfvertex_label_agisFALSE,igraphnetworkgraphswillbedrawnwithoutlabelsvertex.label.distDistancebetweennodeandlabel.Defaultis0.6vertex.label.cexSizeoflabelsDefaultis0.8edge.arrow.sizeSizeofedgesDefaultis0.4vertex.sizeSizeofnodesDefaultis10vertex.shapeYoucanchoosenodeshape.Defaultis'sphere'.Seeshapesvertex.colorColorofnodes.Defaultispink.edge.colorColorofedges.Defaultispink.legend_locationIfcentrality_typeischosen,xina_plot_singleaddthecolorlegendguidingrankofnodesbasedonthecentralityscore.Defaultis'bottomright',butyoucanchooseoneofthese'bottomright','bottom','bottomleft','left','topleft','top','topright','right'and'center'. 36xina_plot_singleflag_unknown_onlyIfthisisTRUE,'xina_plot_bycluster

36 'willplotproteinsthatdonothaveanyprotein
'willplotproteinsthatdonothaveanyprotein-proteininteractioninthegivendatabaseValueAPNGle(XINA_Cluster_Networks.png)displayingprotein-proteininteractionnetworkplotsofalltheclustersandalistcontainingXINAnetworkanalysisresultsPNGimagesofPPInetworkplotsofalltheclustersExamples##thefollowingcodeistoshowhowitworksquickly##loadXINAexampledatadata(xina_example)##loadthepreviouslyprocessedXINAanalysisresults#ifyouwanttolearnhowtorun'xina_analysis',pleasesee\link[XINA]{xina_analysis}data(xina_result_example)#plotcluster#1xina_plot_bycluster(xina_result_example,example_clusters,cl=1)#plotPPInetworkofControlconditionincluster#1xina_plot_bycluster(xina_result_example,example_clusters,cl=1,condition='Control') xina_plot_singlexina_plot_single Descriptionxina_plot_singledrawsprotein-proteininteractionnetworkplotforgiven'protein_list'.Usagexina_plot_single(xina_result,protein_list,centrality_type=NULL,layout_specified="",vertex_label_flag=TRUE,main=NULL,vertex.label.color="black",vertex.color=NA,edge.color="darkgray",vertex.label.dist=0.6,vertex.label.cex=0.8,edge.arrow.size=0.4,vertex.size=10,vertex.shape="sphere",legend_location="bottom",num_breaks=5,dig

37 its_round_up=5,flag_simplify=TRUE,flag_l
its_round_up=5,flag_simplify=TRUE,flag_legend=TRUE) xina_plot_single37Argumentsxina_resultAlistcontainingXINAnetworkanalysisresults.Seexina_analysisprotein_listAvectorofgenenamestodrawaprotein-proteininteractionnetworkgraph.centrality_type'centrality_type'shouldbeoneofc('Degree','Eigenvector','Hub','Author-ity','Closeness','Betweenness')CentralityscoreigraphfunctionDegreedegreeEigenvectoreigen_centralityHubhub_scoreAuthorityauthority_scoreClosenessclosenessBetweennessbetweennesslayout_specifiedThiscanchangenetworklayout.'layout_specied'shouldbeoneofc('sphere','star','gem','tree','circle','random','nicely').XINA'slayoutsarebasedonigraph'slayout.Seelayout_Layoutigraphlayoutnamespherelayout_on_spherestarlayout_as_stargemlayout_with_gemtreelayout_as_treecirclelayout_in_circlerandomlayout_randomlynicelylayout_nicelyDefaultis'layout_nicely'ofigraphvertex_label_flagIfvertex_label_agisTRUE(default),igraphnetworkgraphswillbelabeledbygenenamesIfvertex_label_agisFALSE,igraphnetworkgraphswillbedrawnwithoutlabelsmainTitleofnetworkgure.IFitisNULL(default),itwillbethenumberofplottedproteinsvertex.label.colorColoroflabels.Defaultisblackvertex.c

38 olorColorofnodes.Defaultispink.edge.colo
olorColorofnodes.Defaultispink.edge.colorColorofedges.Defaultispink.vertex.label.distDistancebetweennodeandlabel.Defaultis0.6vertex.label.cexSizeoflabelsDefaultis0.8 38xina_result_exampleedge.arrow.sizeSizeofedgesDefaultis0.4vertex.sizeSizeofnodesDefaultis10vertex.shapeYoucanchoosenodeshape.Defaultis'sphere'.Seeshapeslegend_locationIfcentrality_typeischosen,'xina_plot_single'addsthecolorlegendguidingrankofnodesbasedonthecentralityscore.Defaultis'bottomright',butyoucanchooseoneofthese'bottomright','bottom','bottomleft','left','topleft','top','topright','right'and'center'.num_breaks'num_breaks'isthenumberofranksbasedonnetworkcentrality.Defaultis5.digits_round_upSeeRoundflag_simplifyIfitisTRUE(default),XINAwillexcludeunconnectedproteinsflag_legendIfitisTRUE,alegendwillbeprintedouttogether.ValueAPNGle(XINA_Cluster_Networks.png)displayingprotein-proteininteractionnetworkplotsofalltheclustersandalistcontainingXINAnetworkanalysisresultsExamples##thefollowingcodeistoshowhowitworksquickly##loadXINAexampledatadata(xina_example)##loadthepreviouslyprocessedXINAanalysisresults#ifyouwanttolearnhowtorun'xina_analysis',pleasesee\link[XINA]{xina_analysis}da

39 ta(xina_result_example)#getgenenamesthat
ta(xina_result_example)#getgenenamesthatareclusteredto#21in"Stimulus2"conditionsubgroupsubset(example_clusters$aligned,Stimulus2==21)protein_listsubgroup$`Genename`#Calculateprotein-proteininteractionnetworkxina_plot_single(xina_result_example,protein_list)#Calculateprotein-proteininteractionnetworkandEigenvectorcentralityeigen_infoxina_plot_single(xina_result_example,protein_list,centrality_type='Eigenvector') xina_result_examplePreviouslyprocessedxinaanalysisusingXINA'srandomexampledataAlistcontaining'xina_analysis'results xina_result_example39Description•All_network.PPInetworkofalltheinputproteins•Sub_network.AlistcontainingPPInetworksofeachclusters•Data.XINAclusteringresults.Seexina_clustering•Nodes.Alistofproteinsineachcluster•Conditions.Alistofexperimentalconditionofproteinsineachcluster•Titles.AlistofplottitlesforXINAplotting•out_dir.AdirectorypathstoringXINAnetworkanalysisresults•is_stringdb.False=differentPPIDBandTRUE=STRINGDBFormatAdataframecontainingSTRINGprotein-proteininteractiondataSourceXINA Indexadd_legend,3alluvial,4,7,12,13alluvial_enriched,4alluvial_enrichment_tests,5authority_score,32,

40 35,37betweenness,32,35,37calculate_centr
35,37betweenness,32,35,37calculate_centrality_scores,6closeness,32,35,37count,6,7,10,13default_size,7degree,32,35,37draw_alluvial_plot,7eigen_centrality,32,35,37example_clusters,8extract_data_column,9find_similar_clusters,9generate_count_table,10generate_superset,10get_color_for_nodes,11get_colors,11get_comigrations_by_name,12get_condition_biased_comigrations,13get_enrichment,31get_layout,14get_mTOR_proteins,15get_random_data,15get_stats,16get_theme_blank,16get_unknown_ppi_nodes,17gn,17gn_desc,18hprd_ppi,18hub_score,32,35,37layout_,32,35,37layout_as_star,33,35,37layout_as_tree,33,35,37layout_in_circle,33,35,37layout_nicely,33,35,37layout_on_sphere,33,35,37layout_randomly,33,35,37layout_with_gem,33,35,37length2,19load_previous_results,19make_random_xina_data,20mclustModelNames,29mutate_colors,21organize_clusters,22p.adjust,4plot_clusters,22plot_clusters_all,23plot_condition_compositions,13,21,24plot_enrichment_results,25plot_NA,26rank_centrality,27Round,38scale,29shapes,28,33,35,38string_example,27xina_analysis,17,28,32,34,37xina_clustering,4,7,9,10,12,13,17,21–24,28,29,32,34,39xina_enrichment,25,30xina_plot_all,32xina_plot_bycluster,34xina

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