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pmid:35646901
In Silico Integration of Transcriptome and Interactome Predicts an ETP-ALL-Specific Transcriptional Footprint that Decodes its Developmental Propensity.
Soumyadeep Mukherjee · Arpita Kar · Paramita Paul · Souvik Dey · Avik Biswas · Subhasis Barik
Frontiers in cell and developmental biology · 2022 doi:10.3389/fcell.2022.899752
Paper
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Experiment
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Data
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Analysis
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Execution
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Complete file
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Extensive developmental flexibility of the multipotent ETP-ALL blasts with considerable intra-population heterogeneity in terms of immunophenotype and prognostic parameters might be a target for novel therapeutic interventions. Using a public gene expression dataset (GSE28703) from NCBI GEO DataSets with 12 ETP-ALL and 40 non-ETP-ALL samples, such heterogeneity was found to be reflected in their transcriptome as well. Hub genes were identified from the STRING-derived functional interaction network of genes showing differential expression between ETP-ALL and non-ETP-ALL as well as variable expression across ETP-ALL. Nine genes (KIT, HGF, NT5E, PROM1, CD33, ANPEP, CDH2, IL1B, and CXCL2) among the hubs were further validated as possible diagnostic ETP-ALL markers using another gene expression dataset (GSE78132) with 17 ETP-ALL and 27 non-ETP-ALL samples. Linear dimensionality reduction analysis with the expression levels of the hub genes in ETP-ALL revealed their divergent inclinations towards different hematopoietic lineages, proposing them as novel indicators of lineage specification in the incompletely differentiated ETP-ALL blasts. This further led to the formulation of a personalized lineage score calculation algorithm, which uncovered a considerable B-lineage-bias in a substantial fraction of ETP-ALL subjects from the GSE28703 and GSE78132 cohorts. In addition, STRING-derived physical interactome of the potential biomarkers displayed complete segregation of the B-lineage-skewed markers from other lineage-associated factors, highlighting their distinct functionality and possible druggability in ETP-ALL. A panel of these biomarkers might be useful in pinpointing the dominant lineage specification programmes in the ETP-ALL blasts on a personalized level, urging the development of novel lineage-directed precision therapies as well as repurposing of existing therapies against leukemia of different hematopoietic lineages; which might overcome the drawbacks of conventional chemotherapy.", "claims": [{"id": "claim-method", "statement": "The ability of genes as binary classifiers in discriminating between ETP-ALL and non-ETP-ALL was tested using receiver operating characteristic (ROC) analysis on ROCplot (Fekete and Győrffy, 2019).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35646901", "locator": "sections[8] \"Classifier Performance Analysis\" paragraph 2", "quote": "The ability of genes as binary classifiers in discriminating between ETP-ALL and non-ETP-ALL was tested using receiver operating characteristic (ROC) analysis on ROCplot (Fekete and Győrffy, 2019)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The public microarray gene expression datasets used in this study are available on NCBI GEO DataSets (URL: https://www.ncbi.nlm.nih.gov/gds) against the respective accession numbers: GSE28703, GSE78132, and GSE13159. 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"GSM330306", "GSM330307", "GSM330308", "GSM330309", "GSM330310", "GSM330317", "GSM330318", "GSM330319", "GSM330320", "GSM330321", "GSM330322", "GSM330323", "GSM330324", "GSM330325", "GSM330326", "GSM330327", "GSM330328", "GSM330329", "GSM330330", "GSM330331", "GSM330332", "GSM330333", "GSM330334", "GSM330335", "GSM330336", "GSM330337", "GSM330338", "GSM330339", "GSM330340", "GSM330341", "GSM330342", "GSM330343", "GSM330344", "GSM330345", "GSM330346", "GSM330347", "GSM330348", "GSM330349", "GSM330350", "GSM330351", "GSM330352", "GSM330353", "GSM330354", "GSM330355", "GSM330356", "GSM330357", "GSM330358", "GSM330359", "GSM330360", "GSM330361", "GSM330362", "GSM330363", "GSM330364", "GSM330365", "GSM330366", "GSM330367", "GSM330368", "GSM330369", "GSM330370", "GSM330371", "GSM330372", "GSM330373", "GSM330374", "GSM330375", "GSM330376", "GSM330377", "GSM330378", "GSM330379", "GSM330380", "GSM330381", "GSM330382", "GSM330383", "GSM330384", "GSM330385", "GSM330386", "GSM330387", "GSM330388", "GSM330389", "GSM330390", "GSM330391", "GSM330392", "GSM330393", "GSM330394", "GSM330395", "GSM330396", "GSM330397", "GSM330398", "GSM330399", "GSM330400", "GSM330401", "GSM330402", "GSM330403", "GSM330404", "GSM330405", "GSM330406", "GSM330407", "GSM330408", "GSM330409", "GSM330410", "GSM330411", "GSM330412", "GSM330413", "GSM330414", "GSM330415", "GSM330416", "GSM330417", "GSM330418", "GSM330419", "GSM330420", "GSM330421", "GSM330422", "GSM330423", "GSM330424", "GSM330425", "GSM330426", "GSM330427", "GSM330428", "GSM330429", "GSM330430", "GSM330431", "GSM330432", "GSM330433", "GSM330434", "GSM330435", "GSM330436", "GSM330437", "GSM330438", "GSM330439", "GSM330440", "GSM330441", "GSM330442", "GSM330443", "GSM330444", "GSM330445", "GSM330446", "GSM330447", "GSM330448", "GSM330449", "GSM330450", "GSM330451", "GSM330452", "GSM330453", "GSM330454", "GSM330455", "GSM330456", "GSM330457", "GSM330458", "GSM330459", "GSM330460", "GSM330461", "GSM330462", "GSM330463", "GSM330464", "GSM330465", "GSM330466", "GSM330467", "GSM330468", "GSM330469", "GSM330470", "GSM330471", "GSM330472", "GSM330473", "GSM330474", "GSM330475", "GSM330476", "GSM330477", "GSM330478", "GSM330479", "GSM330480", "GSM330481", "GSM330482", "GSM330483", "GSM330484", "GSM330485", "GSM330486", "GSM330487", "GSM330488", "GSM330489", "GSM330490", "GSM330491", "GSM330492", "GSM330493", "GSM330494", "GSM330495", "GSM330496", "GSM330497", "GSM330498", "GSM330499", "GSM330500", "GSM330501", "GSM330502", "GSM330503", "GSM330504", "GSM330505", "GSM330506", "GSM330507", "GSM330508", "GSM330509", "GSM330510", "GSM330511", "GSM330512", "GSM330513", "GSM330514", "GSM330515", "GSM330516", "GSM330517", "GSM330518", "GSM330519", "GSM330520", "GSM330521", "GSM330522", "GSM330523", "GSM330524", "GSM330525", "GSM330526", "GSM330527", "GSM330528", "GSM330529", "GSM330530", "GSM330531", "GSM330532", "GSM330533", "GSM330534", "GSM330535", "GSM330536", "GSM330537", "GSM330538", "GSM330539", "GSM330540", "GSM330541", "GSM330542", "GSM330543", "GSM330544", "GSM330545", "GSM330546", "GSM330547", "GSM330548", "GSM330549", "GSM330550", "GSM330551", "GSM330552", "GSM330553", "GSM330554", "GSM330555", "GSM330556", "GSM330557", "GSM330558", "GSM330559", "GSM330560", "GSM330561", "GSM330562", "GSM330563", "GSM330564", "GSM330565", "GSM330566", "GSM330567", "GSM330568", "GSM330569", "GSM330570", "GSM330571", "GSM330572", "GSM330573", "GSM330574", "GSM330575", "GSM330576", "GSM330577", "GSM330578", "GSM330579", "GSM330580", "GSM330581", "GSM330582", "GSM330583", "GSM330584", "GSM330585", "GSM330586", "GSM330587", "GSM330588", "GSM330589", "GSM330590", "GSM330591", "GSM330592", "GSM330593", "GSM330594", "GSM330595", "GSM330596", "GSM330597", "GSM330598", "GSM330599", "GSM330600", "GSM330601", "GSM330602", "GSM330603", "GSM330604", "GSM330605", "GSM330606", "GSM330607", "GSM330608", "GSM330609", "GSM330610", "GSM330611", "GSM330612", "GSM330613", "GSM330614", "GSM330615", "GSM330616", "GSM330617", "GSM330618", "GSM330619", "GSM330620", "GSM330621", "GSM330622", "GSM330623", "GSM330624", "GSM330625", "GSM330626", "GSM330627", "GSM330628", "GSM330629", "GSM330630", "GSM330631", "GSM330632", "GSM330633", "GSM330634", "GSM330635", "GSM330636", "GSM330637", "GSM330638", "GSM330639", "GSM330640", "GSM330641", "GSM330642", "GSM330643", "GSM330644", "GSM330645", "GSM330646", "GSM330647", "GSM330648", "GSM330649", "GSM330650", "GSM330651", "GSM330652", "GSM330653", "GSM330654", "GSM330655", "GSM330656", "GSM330657", "GSM330658", "GSM330659", "GSM330660", "GSM330661", "GSM330662", "GSM330663", "GSM330664", "GSM330665", "GSM330666", "GSM330667", "GSM330668", "GSM330669", "GSM330670", "GSM330671", "GSM330672", "GSM330673", "GSM330674", "GSM330675", "GSM330676", "GSM330677", "GSM330678", "GSM330679", "GSM330680", "GSM330681", "GSM330682", "GSM330683", "GSM330684", "GSM330685", "GSM330686", "GSM330687", "GSM330688", "GSM330689", "GSM330690", "GSM330691", "GSM330692", "GSM330693", "GSM330694", "GSM330695", "GSM330696", "GSM330697", "GSM330698", "GSM330699", "GSM330700", "GSM330701", "GSM330702", "GSM330703", "GSM330704", "GSM330705", "GSM330706", "GSM330707", "GSM330708", "GSM330709", "GSM330710", "GSM330711", "GSM330712", "GSM330713", "GSM330714", "GSM330715", "GSM330716", "GSM330717", "GSM330718", "GSM330719", "GSM330720", "GSM330721", "GSM330722", "GSM330723", "GSM330724", "GSM330725", "GSM330726", "GSM330727", "GSM330728", "GSM330729", "GSM330730", "GSM330731", "GSM330732", "GSM330733", "GSM330734", "GSM330735", "GSM330736", "GSM330737", "GSM330738", "GSM330739", "GSM330740", "GSM330741", "GSM330742", "GSM330743", "GSM330744", "GSM330745", "GSM330746", "GSM330747", "GSM330748", "GSM330749", "GSM330750", "GSM330751", "GSM330752", "GSM330753", "GSM330754", "GSM330755", "GSM330756", "GSM330757", "GSM330758", "GSM330759", "GSM330760", "GSM330761", "GSM330762", "GSM330763", "GSM330764", "GSM330765", "GSM330766", "GSM330767", "GSM330768", "GSM330769", "GSM330770", "GSM330771", "GSM330772", "GSM330773", "GSM330774", "GSM330775", "GSM330776", "GSM330777", "GSM330778", "GSM330779", "GSM330780", "GSM330781", "GSM330782", "GSM330783", "GSM330784", "GSM330785", "GSM330786", "GSM330787", "GSM330788", "GSM330789", "GSM330790", "GSM330791", "GSM330792", "GSM330793", "GSM330794", "GSM330795", "GSM330796", "GSM330797", "GSM330798", "GSM330799", "GSM330800", "GSM330801", "GSM330802", "GSM330803", "GSM330804", "GSM330805", "GSM330806", "GSM330807", "GSM330808", "GSM330809", "GSM330810", "GSM330811", "GSM330812", "GSM330813", "GSM330814", "GSM330815", "GSM330816", "GSM330817", "GSM330818", "GSM330819", "GSM330820", "GSM330821", "GSM330822", "GSM330823", "GSM330824", "GSM330825", "GSM330826", "GSM330827", "GSM330828", "GSM330829", "GSM330830", "GSM330831", "GSM330832", "GSM330833", "GSM330834", "GSM330835", "GSM330836", "GSM330837", "GSM330838", "GSM330839", "GSM330840", "GSM330841", "GSM330842", "GSM330843", "GSM330844", "GSM330845", "GSM330846", "GSM330847", "GSM330848", "GSM330849", "GSM330850", "GSM330851", "GSM330852", "GSM330853", "GSM330854", "GSM330855", "GSM330856", "GSM330857", "GSM330858", "GSM330859", "GSM330860", "GSM330861", "GSM330862", "GSM330863", "GSM330864", "GSM330865", "GSM330866", "GSM330867", "GSM330868", "GSM330869", "GSM330870", "GSM330871", "GSM330872", "GSM330873", "GSM330874", "GSM330875", "GSM330876", "GSM330877", "GSM330878", "GSM330879", "GSM330880", "GSM330881", "GSM330882", "GSM330883", "GSM330884", "GSM330885", "GSM330886", "GSM330887", "GSM330888", "GSM330889", "GSM330890", "GSM330891", "GSM330892", "GSM330893", "GSM330894", "GSM330895", "GSM330896", "GSM330897", "GSM330898", "GSM330899", "GSM330900", "GSM330901", "GSM330902", "GSM330903", "GSM330904", "GSM330905", "GSM330906", "GSM330907", "GSM330908", "GSM330909", "GSM330910", "GSM330911", "GSM330912", "GSM330913", "GSM330914", "GSM330915", "GSM330916", "GSM330917", "GSM330918", "GSM330919", "GSM330920", "GSM330921", "GSM330922", "GSM330923", "GSM330924", "GSM330925", "GSM330926", "GSM330927", "GSM330928", "GSM330929", "GSM330930", "GSM330931", "GSM330932", "GSM330933", "GSM330934", "GSM330935", "GSM330936", "GSM330937", "GSM330938", "GSM330939", "GSM330940", "GSM330941", "GSM330942", "GSM330943", "GSM330944", "GSM330945", "GSM330946", "GSM330947", "GSM330948", "GSM330949", "GSM330950", "GSM330951", "GSM330952", "GSM330953", "GSM330954", "GSM330955", "GSM330956", "GSM330957", "GSM330958", "GSM330959", "GSM330960", "GSM330961", "GSM330962", "GSM330963", "GSM330964", "GSM330965", "GSM330966", "GSM330967", "GSM330968", "GSM330969", "GSM330970", "GSM330971", "GSM330972", "GSM330973", "GSM330974", "GSM330975", "GSM330976", "GSM330977", "GSM330978", "GSM330979", "GSM330980", "GSM330981", "GSM330982", "GSM330983", "GSM330984", "GSM330985", "GSM330986", "GSM330987", "GSM330988", "GSM330989", "GSM330990", "GSM330991", "GSM330992", "GSM330993", "GSM330994", "GSM330995", "GSM330996", "GSM330997", "GSM330998", "GSM330999", "GSM331000", "GSM331001", "GSM331002", "GSM331003", "GSM331004", "GSM331005", "GSM331006", "GSM331007", "GSM331008", "GSM331009", "GSM331010", "GSM331011", "GSM331012", "GSM331013", "GSM331014", "GSM331015", "GSM331016", "GSM331017", "GSM331018", "GSM331019", "GSM331020", "GSM331021", "GSM331022", "GSM331023", "GSM331024", "GSM331025", "GSM331026", "GSM331027", "GSM331028", "GSM331029", "GSM331030", "GSM331031", "GSM331032", "GSM331033", "GSM331034", "GSM331035", "GSM331036", "GSM331037", "GSM331038", "GSM331039", "GSM331040", "GSM331041", "GSM331042", "GSM331043", "GSM331044", "GSM331045", "GSM331046", "GSM331047", "GSM331048", "GSM331049", "GSM331050", "GSM331051", "GSM331052", "GSM331053", "GSM331054", "GSM331055", "GSM331056", "GSM331057", "GSM331058", "GSM331059", "GSM331060", "GSM331061", "GSM331062", "GSM331063", "GSM331064", "GSM331065", "GSM331066", "GSM331067", "GSM331068", "GSM331069", "GSM331070", "GSM331071", "GSM331072", "GSM331073", "GSM331074", "GSM331075", "GSM331076", "GSM331077", "GSM331078", "GSM331079", "GSM331080", "GSM331081", "GSM331082", "GSM331083", "GSM331084", "GSM331085", "GSM331086", "GSM331087", "GSM331088", "GSM331089", "GSM331090", "GSM331091", "GSM331092", "GSM331093", "GSM331094", "GSM331095", "GSM331096", "GSM331097", "GSM331098", "GSM331099", "GSM331100", "GSM331101", "GSM331102", "GSM331103", "GSM331104", "GSM331105", "GSM331106", "GSM331107", "GSM331108", "GSM331109", "GSM331110", "GSM331111", "GSM331112", "GSM331113", "GSM331114", "GSM331115", "GSM331116", "GSM331117", "GSM331118", "GSM331119", "GSM331120", "GSM331121", "GSM331122", "GSM331123", "GSM331124", "GSM331125", "GSM331126", "GSM331127", "GSM331128", "GSM331129", "GSM331130", "GSM331131", "GSM331132", "GSM331133", "GSM331134", "GSM331135", "GSM331136", "GSM331137", "GSM331138", "GSM331139", "GSM331140", "GSM331141", "GSM331142", "GSM331143", "GSM331144", "GSM331145", "GSM331146", "GSM331147", "GSM331148", "GSM331149", "GSM331150", "GSM331151", "GSM331152", "GSM331153", "GSM331154", "GSM331155", "GSM331156", "GSM331157", "GSM331158", "GSM331159", "GSM331160", "GSM331161", "GSM331162", "GSM331163", "GSM331164", "GSM331165", "GSM331166", "GSM331167", "GSM331168", "GSM331169", "GSM331170", "GSM331171", "GSM331172", "GSM331173", "GSM331174", "GSM331175", "GSM331176", "GSM331177", "GSM331178", "GSM331179", "GSM331180", "GSM331181", "GSM331182", "GSM331183", "GSM331184", "GSM331185", "GSM331186", "GSM331187", "GSM331188", "GSM331189", "GSM331190", "GSM331191", "GSM331192", "GSM331193", "GSM331194", "GSM331195", "GSM331196", "GSM331197", "GSM331198", "GSM331199", "GSM331200", "GSM331201", "GSM331202", "GSM331203", "GSM331204", "GSM331205", "GSM331206", "GSM331207", "GSM331208", "GSM331209", "GSM331210", "GSM331211", "GSM331212", "GSM331213", "GSM331214", "GSM331215", "GSM331216", "GSM331217", "GSM331218", "GSM331219", "GSM331220", "GSM331221", "GSM331222", "GSM331223", "GSM331224", "GSM331225", "GSM331226", "GSM331227", "GSM331228", "GSM331229", "GSM331230", "GSM331231", "GSM331232", "GSM331233", "GSM331234", "GSM331235", 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