Schematic overview of the cellular and molecular mechanisms involved in the cancer progression, including the proposed cellular and molecular mechanisms in cancer cells trajectory. AT1: alveolar type 1 cells; AT2: alveolar type 2 cells; AAH: atypical adenomatous hyperplasia; AIS: adenocarcinoma in situ; MIA: minimally invasive adenocarcinoma; IA: invasive adenocarcinoma; EMT: epithelial-mesenchymal transition

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Center for Computational Systems Medicine
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Gene summary

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Malignant transformation analysis

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Malignant transformation related pathway analysis

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Cell-cell communication analysis

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Single-cell gene regulatory network inference analysis

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Somatic mutation of malignant transformation related genes

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Related drugs of malignant transformation related genes

Gene: MLKL

Gene summary for MLKL

check button Gene summary.

Gene informationSpeciesHuman
Gene symbol

MLKL

Gene ID

197259

Gene namemixed lineage kinase domain like pseudokinase
Gene AliashMLKL
Cytomap16q23.1
Gene Typeprotein-coding
GO ID

GO:0002376

UniProtAcc

Q8NB16


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Malignant transformation analysis

check button Identification of the aberrant gene expression in precancerous and cancerous lesions by comparing the gene expression of stem-like cells in diseased tissues with normal stem cells
check button Malignant transformation involving gene list.
Entrez IDSymbolReplicatesSpeciesOrganTissueAdj P-valueLog2FCMalignancy
197259MLKLP4T-EHumanEsophagusESCC1.18e-021.52e-010.1323
197259MLKLP11T-EHumanEsophagusESCC1.93e-052.91e-010.1426
197259MLKLP20T-EHumanEsophagusESCC1.15e-039.61e-020.1124
197259MLKLP21T-EHumanEsophagusESCC1.66e-062.36e-010.1617
197259MLKLP23T-EHumanEsophagusESCC2.29e-031.47e-010.108
197259MLKLP24T-EHumanEsophagusESCC1.71e-121.25e-010.1287
197259MLKLP26T-EHumanEsophagusESCC8.87e-058.44e-020.1276
197259MLKLP28T-EHumanEsophagusESCC4.17e-031.05e-010.1149
197259MLKLP32T-EHumanEsophagusESCC4.71e-057.60e-020.1666
197259MLKLP36T-EHumanEsophagusESCC8.81e-081.96e-010.1187
197259MLKLP48T-EHumanEsophagusESCC2.19e-034.50e-020.0959
197259MLKLP52T-EHumanEsophagusESCC4.45e-123.41e-010.1555
197259MLKLP62T-EHumanEsophagusESCC3.56e-143.09e-010.1302
197259MLKLP74T-EHumanEsophagusESCC2.73e-021.59e-010.1479
197259MLKLP75T-EHumanEsophagusESCC2.39e-032.93e-010.1125
197259MLKLP76T-EHumanEsophagusESCC1.56e-068.48e-020.1207
197259MLKLP80T-EHumanEsophagusESCC4.27e-133.01e-010.155
197259MLKLP83T-EHumanEsophagusESCC3.10e-186.01e-010.1738
197259MLKLP89T-EHumanEsophagusESCC6.22e-095.13e-010.1752
197259MLKLP107T-EHumanEsophagusESCC1.12e-061.85e-010.171
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check button Transcriptomic changes along malignancy continuum.
TissueExpression DynamicsAbbreviation
EsophagusThe image shows the transcriptomic changes along malignancy continuum.log2FC in expression of this searched gene in stem-like cells from each diseased tissue sample relative to stem-like cells in normal samples in each tissue plotted against the malignancy continuum. Samples are colored based on if they are from different disease stage.ESCC: Esophageal squamous cell carcinoma
HGIN: High-grade intraepithelial neoplasias
LGIN: Low-grade intraepithelial neoplasias
LiverThe image shows the transcriptomic changes along malignancy continuum.log2FC in expression of this searched gene in stem-like cells from each diseased tissue sample relative to stem-like cells in normal samples in each tissue plotted against the malignancy continuum. Samples are colored based on if they are from different disease stage.HCC: Hepatocellular carcinoma
NAFLD: Non-alcoholic fatty liver disease
∗log2FC in expression of this searched gene in stem-like cells from each diseased tissue sample relative to stem-like cells in normal samples in each tissue plotted against the malignancy continuum. Samples are colored based on if they are from different disease stage.

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Malignant transformation related pathway analysis

check buttonFind out the enriched GO biological processes and KEGG pathways involved in transition from healthy to precancer to cancer
check button Figure of enriched GO biological processes.
TissueDisease StageEnriched GO biological Processes
ColorectumADGO analysis - Figure of enriched GO biological processes: Top 15 enriched GO BP terms are showed in the bar plot of each disease state in each tissue. Each row represents a significant GO biological process which is colored according to the -log10(p.adjust).
ColorectumSERGO analysis - Figure of enriched GO biological processes: Top 15 enriched GO BP terms are showed in the bar plot of each disease state in each tissue. Each row represents a significant GO biological process which is colored according to the -log10(p.adjust).
ColorectumMSSGO analysis - Figure of enriched GO biological processes: Top 15 enriched GO BP terms are showed in the bar plot of each disease state in each tissue. Each row represents a significant GO biological process which is colored according to the -log10(p.adjust).
ColorectumMSI-HGO analysis - Figure of enriched GO biological processes: Top 15 enriched GO BP terms are showed in the bar plot of each disease state in each tissue. Each row represents a significant GO biological process which is colored according to the -log10(p.adjust).
ColorectumFAPGO analysis - Figure of enriched GO biological processes: Top 15 enriched GO BP terms are showed in the bar plot of each disease state in each tissue. Each row represents a significant GO biological process which is colored according to the -log10(p.adjust).
∗Top 15 enriched GO BP terms are showed in the bar plot of each disease state in each tissue. Each row represents a significant GO biological process which is colored according to the -log10(p.adjust).
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check button Enriched GO biological processes.
GO IDTissueDisease StageDescriptionGene RatioBg Ratiopvaluep.adjustCount
GO:000961518EsophagusESCCresponse to virus238/8552367/187236.65e-143.32e-12238
GO:00516075EsophagusESCCdefense response to virus171/8552265/187233.91e-101.05e-08171
GO:01405465EsophagusESCCdefense response to symbiont171/8552265/187233.91e-101.05e-08171
GO:00973002EsophagusESCCprogrammed necrotic cell death32/855247/187231.59e-037.43e-0332
GO:00512592EsophagusESCCprotein complex oligomerization130/8552238/187233.29e-031.36e-02130
GO:00702654EsophagusESCCnecrotic cell death39/855262/187234.68e-031.82e-0239
GO:000961511LiverHCCresponse to virus210/7958367/187237.32e-091.86e-07210
GO:00516071LiverHCCdefense response to virus151/7958265/187231.27e-061.85e-05151
GO:01405461LiverHCCdefense response to symbiont151/7958265/187231.27e-061.85e-05151
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check button Enriched KEGG pathways.
Pathway IDTissueDisease StageDescriptionGene RatioBg Ratiopvaluep.adjustqvalueCount
hsa05132211EsophagusESCCSalmonella infection191/4205249/84656.51e-195.45e-172.79e-17191
hsa0466810EsophagusESCCTNF signaling pathway89/4205114/84653.36e-104.01e-092.06e-0989
hsa046234EsophagusESCCCytosolic DNA-sensing pathway49/420575/84654.35e-031.12e-025.74e-0349
hsa05132310EsophagusESCCSalmonella infection191/4205249/84656.51e-195.45e-172.79e-17191
hsa0466817EsophagusESCCTNF signaling pathway89/4205114/84653.36e-104.01e-092.06e-0989
hsa0462311EsophagusESCCCytosolic DNA-sensing pathway49/420575/84654.35e-031.12e-025.74e-0349
hsa0513242LiverHCCSalmonella infection178/4020249/84655.90e-151.98e-131.10e-13178
hsa046684LiverHCCTNF signaling pathway73/4020114/84652.53e-041.19e-036.63e-0473
hsa0513252LiverHCCSalmonella infection178/4020249/84655.90e-151.98e-131.10e-13178
hsa0466811LiverHCCTNF signaling pathway73/4020114/84652.53e-041.19e-036.63e-0473
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Cell-cell communication analysis

check buttonIdentification of potential cell-cell interactions between two cell types and their ligand-receptor pairs for different disease states
LigandReceptorLRpairPathwayTissueDisease Stage
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Single-cell gene regulatory network inference analysis

check buttonFind out the significant the regulons (TFs) and the target genes of each regulon across cell types for different disease states
TFCell TypeTissueDisease StageTarget GeneRSSRegulon Activity
∗The dot plots of a searched regulon are shown for all cell subpopulations in each disease state of each tissue based on the regulon specific score inferred using pySCENIC and by calculating the average expression.
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Somatic mutation of malignant transformation related genes

check buttonAnnotation of somatic variants for genes involved in malignant transformation
Hugo SymbolVariant ClassVariant ClassificationdbSNP RSHGVScHGVSpHGVSp ShortSWISSPROTBIOTYPESIFTPolyPhenTumor Sample BarcodeTissueHistologySexAgeStageTherapy TypesDrugsOutcome
MLKLSNVMissense_Mutationc.485N>Cp.Leu162Prop.L162PQ8NB16protein_codingtolerated(0.06)possibly_damaging(0.823)TCGA-AO-A128-01Breastbreast invasive carcinomaFemale<65I/IIChemotherapydoxorubicinSD
MLKLinsertionIn_Frame_Insnovelc.576_577insCTTAATAAATATCTTTTTTTGTGTGTGTGTGGAGACGTAGTCTCATTCp.Gln192_Ile193insLeuAsnLysTyrLeuPheLeuCysValCysGlyAspValValSerPhep.Q192_I193insLNKYLFLCVCGDVVSFQ8NB16protein_codingTCGA-A2-A0EO-01Breastbreast invasive carcinomaFemale<65I/IIHormone TherapytamoxiphenSD
MLKLinsertionIn_Frame_Insnovelc.1348_1349insATTATTTCCTCGATGCAGACTTTTATCTCAp.Ala450delinsAspTyrPheLeuAspAlaAspPheTyrLeuThrp.A450delinsDYFLDADFYLTQ8NB16protein_codingTCGA-AR-A0TY-01Breastbreast invasive carcinomaFemale<65I/IIUnspecificPaclitaxelPD
MLKLSNVMissense_Mutationc.287N>Cp.Ile96Thrp.I96TQ8NB16protein_codingtolerated(0.27)benign(0.3)TCGA-FU-A3HZ-01Cervixcervical & endocervical cancerFemale<65I/IIChemotherapycisplatinCR
MLKLSNVMissense_Mutationnovelc.753N>Gp.Ile251Metp.I251MQ8NB16protein_codingdeleterious(0)possibly_damaging(0.828)TCGA-IR-A3LK-01Cervixcervical & endocervical cancerFemale>=65I/IIChemotherapycisplatinPD
MLKLSNVMissense_Mutationrs750054698c.1133N>Tp.Ser378Leup.S378LQ8NB16protein_codingdeleterious(0)probably_damaging(0.917)TCGA-Q1-A73P-01Cervixcervical & endocervical cancerFemale<65I/IIUnknownUnknownSD
MLKLSNVMissense_Mutationnovelc.563T>Cp.Ile188Thrp.I188TQ8NB16protein_codingtolerated(0.2)benign(0.01)TCGA-5M-AAT6-01Colorectumcolon adenocarcinomaFemale<65III/IVUnknownUnknownPD
MLKLSNVMissense_Mutationrs377446580c.827N>Tp.Pro276Leup.P276LQ8NB16protein_codingdeleterious(0.01)benign(0.117)TCGA-AA-3663-01Colorectumcolon adenocarcinomaMale<65I/IIUnknownUnknownSD
MLKLSNVMissense_Mutationrs771880061c.811N>Tp.Asp271Tyrp.D271YQ8NB16protein_codingdeleterious(0)probably_damaging(0.923)TCGA-AA-3939-01Colorectumcolon adenocarcinomaMale>=65I/IIUnknownUnknownSD
MLKLSNVMissense_Mutationrs201376894c.275G>Ap.Ser92Asnp.S92NQ8NB16protein_codingtolerated(0.54)benign(0.01)TCGA-AZ-4615-01Colorectumcolon adenocarcinomaMale>=65III/IVChemotherapyxelodaPD
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Related drugs of malignant transformation related genes

check buttonIdentification of chemicals and drugs interact with genes involved in malignant transfromation
(DGIdb 4.0)
Entrez IDSymbolCategoryInteraction TypesDrug Claim NameDrug NamePMIDs
197259MLKLENZYME, DRUGGABLE GENOME, SERINE THREONINE KINASE, KINASEinhibitor336446900
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