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: NEDD4L

Gene summary for NEDD4L

check button Gene summary.

Gene informationSpeciesHuman
Gene symbol

NEDD4L

Gene ID

23327

Gene nameNEDD4 like E3 ubiquitin protein ligase
Gene AliasNEDD4-2
Cytomap18q21.31
Gene Typeprotein-coding
GO ID

GO:0000209

UniProtAcc

A0A024R2A4


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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
23327NEDD4LCCI_1HumanCervixCC7.51e-251.54e+000.528
23327NEDD4LCCI_2HumanCervixCC3.57e-151.54e+000.5249
23327NEDD4LCCI_3HumanCervixCC1.32e-211.33e+000.516
23327NEDD4LCCII_1HumanCervixCC1.56e-094.95e-010.3249
23327NEDD4Lsample1HumanCervixCC3.05e-095.17e-010.0959
23327NEDD4LH2HumanCervixHSIL_HPV5.87e-062.28e-010.0632
23327NEDD4LT1HumanCervixCC1.63e-226.34e-010.0918
23327NEDD4LHTA11_3410_2000001011HumanColorectumAD1.20e-24-6.52e-010.0155
23327NEDD4LHTA11_2951_2000001011HumanColorectumAD1.17e-07-9.52e-010.0216
23327NEDD4LHTA11_347_2000001011HumanColorectumAD1.01e-085.69e-01-0.1954
23327NEDD4LHTA11_411_2000001011HumanColorectumSER1.05e-101.18e+00-0.2602
23327NEDD4LHTA11_2112_2000001011HumanColorectumSER1.25e-025.58e-01-0.2196
23327NEDD4LHTA11_9341_2000001011HumanColorectumSER3.57e-02-5.89e-01-0.00410000000000005
23327NEDD4LHTA11_866_3004761011HumanColorectumAD2.46e-04-4.98e-010.096
23327NEDD4LHTA11_8622_2000001021HumanColorectumSER4.51e-02-5.17e-010.0528
23327NEDD4LHTA11_99999970781_79442HumanColorectumMSS2.13e-04-3.57e-010.294
23327NEDD4LHTA11_99999965104_69814HumanColorectumMSS2.28e-034.10e-010.281
23327NEDD4LHTA11_99999971662_82457HumanColorectumMSS1.79e-12-4.95e-010.3859
23327NEDD4LHTA11_99999973899_84307HumanColorectumMSS3.84e-14-9.36e-010.2585
23327NEDD4LHTA11_99999974143_84620HumanColorectumMSS1.04e-38-8.51e-010.3005
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check button Transcriptomic changes along malignancy continuum.
TissueExpression DynamicsAbbreviation
CervixThe 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.CC: Cervix cancer
HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
N_HPV: HPV-infected normal cervix
Colorectum (GSE201348)The 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.FAP: Familial adenomatous polyposis
CRC: Colorectal cancer
Colorectum (HTA11)The 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.AD: Adenomas
SER: Sessile serrated lesions
MSI-H: Microsatellite-high colorectal cancer
MSS: Microsatellite stable colorectal cancer
EndometriumThe 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.AEH: Atypical endometrial hyperplasia
EEC: Endometrioid Cancer
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
GCThe 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.CAG: Chronic atrophic gastritis
CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
CSG: Chronic superficial gastritis
GC: Gastric cancer
SIM: Severe intestinal metaplasia
WIM: Wild intestinal metaplasia
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
LungThe 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.AAH: Atypical adenomatous hyperplasia
AIS: Adenocarcinoma in situ
IAC: Invasive lung adenocarcinoma
MIA: Minimally invasive adenocarcinoma
Oral CavityThe 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.EOLP: Erosive Oral lichen planus
LP: leukoplakia
NEOLP: Non-erosive oral lichen planus
OSCC: Oral squamous cell carcinoma
ProstateThe 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.BPH: Benign Prostatic Hyperplasia
SkinThe 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.AK: Actinic keratosis
cSCC: Cutaneous squamous cell carcinoma
SCCIS:squamous cell carcinoma in situ
ThyroidThe 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.ATC: Anaplastic thyroid cancer
HT: Hashimoto's thyroiditis
PTC: Papillary thyroid cancer
∗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:004217610CervixCCregulation of protein catabolic process104/2311391/187239.39e-159.36e-12104
GO:002260410CervixCCregulation of cell morphogenesis84/2311309/187231.00e-124.29e-1084
GO:004573210CervixCCpositive regulation of protein catabolic process65/2311231/187237.44e-111.39e-0865
GO:001049810CervixCCproteasomal protein catabolic process111/2311490/187238.98e-111.58e-08111
GO:000989610CervixCCpositive regulation of catabolic process109/2311492/187235.26e-106.99e-08109
GO:004316110CervixCCproteasome-mediated ubiquitin-dependent protein catabolic process91/2311412/187231.65e-081.25e-0691
GO:00002097CervixCCprotein polyubiquitination58/2311236/187231.57e-077.41e-0658
GO:00163587CervixCCdendrite development58/2311243/187234.52e-071.76e-0558
GO:00109757CervixCCregulation of neuron projection development88/2311445/187234.26e-061.09e-0488
GO:00709366CervixCCprotein K48-linked ubiquitination22/231165/187235.56e-061.38e-0422
GO:003164710CervixCCregulation of protein stability63/2311298/187231.14e-052.45e-0463
GO:00160498CervixCCcell growth92/2311482/187231.16e-052.49e-0492
GO:00301008CervixCCregulation of endocytosis47/2311211/187233.65e-055.82e-0447
GO:00458077CervixCCpositive regulation of endocytosis27/2311100/187235.55e-058.10e-0427
GO:00459277CervixCCpositive regulation of growth53/2311259/187231.33e-041.64e-0353
GO:00015588CervixCCregulation of cell growth77/2311414/187231.40e-041.70e-0377
GO:19023059CervixCCregulation of sodium ion transmembrane transport19/231168/187234.21e-044.25e-0319
GO:00303077CervixCCpositive regulation of cell growth36/2311166/187234.84e-044.75e-0336
GO:00300487CervixCCactin filament-based movement29/2311127/187236.91e-046.33e-0329
GO:00486386CervixCCregulation of developmental growth61/2311330/187237.69e-046.85e-0361
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check button Enriched KEGG pathways.
Pathway IDTissueDisease StageDescriptionGene RatioBg Ratiopvaluep.adjustqvalueCount
hsa0412014CervixCCUbiquitin mediated proteolysis49/1267142/84654.26e-097.68e-084.54e-0849
hsa0453020CervixCCTight junction49/1267169/84651.87e-061.78e-051.05e-0549
hsa0414418CervixCCEndocytosis64/1267251/84656.97e-066.10e-053.61e-0564
hsa0412015CervixCCUbiquitin mediated proteolysis49/1267142/84654.26e-097.68e-084.54e-0849
hsa04530110CervixCCTight junction49/1267169/84651.87e-061.78e-051.05e-0549
hsa0414419CervixCCEndocytosis64/1267251/84656.97e-066.10e-053.61e-0564
hsa04144ColorectumADEndocytosis111/2092251/84655.95e-121.42e-109.08e-11111
hsa04530ColorectumADTight junction76/2092169/84655.49e-099.69e-086.18e-0876
hsa04120ColorectumADUbiquitin mediated proteolysis58/2092142/84651.46e-051.53e-049.76e-0558
hsa041441ColorectumADEndocytosis111/2092251/84655.95e-121.42e-109.08e-11111
hsa045301ColorectumADTight junction76/2092169/84655.49e-099.69e-086.18e-0876
hsa041201ColorectumADUbiquitin mediated proteolysis58/2092142/84651.46e-051.53e-049.76e-0558
hsa041442ColorectumSEREndocytosis81/1580251/84651.14e-072.36e-061.71e-0681
hsa045302ColorectumSERTight junction59/1580169/84653.24e-075.98e-064.34e-0659
hsa041202ColorectumSERUbiquitin mediated proteolysis39/1580142/84656.18e-033.66e-022.66e-0239
hsa041443ColorectumSEREndocytosis81/1580251/84651.14e-072.36e-061.71e-0681
hsa045303ColorectumSERTight junction59/1580169/84653.24e-075.98e-064.34e-0659
hsa041203ColorectumSERUbiquitin mediated proteolysis39/1580142/84656.18e-033.66e-022.66e-0239
hsa041444ColorectumMSSEndocytosis102/1875251/84651.85e-114.43e-102.71e-10102
hsa045304ColorectumMSSTight junction66/1875169/84654.10e-076.25e-063.83e-0666
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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
NEDD4LSNVMissense_Mutationc.1937C>Ap.Ala646Aspp.A646DQ96PU5protein_codingdeleterious(0)probably_damaging(0.998)TCGA-A2-A25E-01Breastbreast invasive carcinomaFemale<65III/IVChemotherapycytoxanPD
NEDD4LSNVMissense_Mutationc.2518A>Gp.Ile840Valp.I840VQ96PU5protein_codingtolerated(0.09)benign(0.127)TCGA-A8-A094-01Breastbreast invasive carcinomaFemale>=65I/IIUnknownUnknownSD
NEDD4LSNVMissense_Mutationc.2003T>Ap.Phe668Tyrp.F668YQ96PU5protein_codingdeleterious(0)probably_damaging(0.999)TCGA-A8-A09K-01Breastbreast invasive carcinomaFemale>=65I/IIUnknownUnknownSD
NEDD4LSNVMissense_Mutationc.2848N>Gp.Pro950Alap.P950AQ96PU5protein_codingdeleterious(0.02)benign(0.031)TCGA-AN-A03Y-01Breastbreast invasive carcinomaFemale>=65I/IIUnknownUnknownSD
NEDD4LSNVMissense_Mutationc.1402N>Gp.Arg468Glyp.R468GQ96PU5protein_codingtolerated(0.1)benign(0.048)TCGA-BH-A0B9-01Breastbreast invasive carcinomaFemale<65I/IIChemotherapycyclophosphamideSD
NEDD4LSNVMissense_Mutationc.229G>Cp.Glu77Glnp.E77QQ96PU5protein_codingdeleterious(0)probably_damaging(0.954)TCGA-BH-A0HP-01Breastbreast invasive carcinomaFemale>=65III/IVChemotherapydoxorubicinSD
NEDD4LSNVMissense_Mutationc.532G>Cp.Asp178Hisp.D178HQ96PU5protein_codingdeleterious(0)possibly_damaging(0.897)TCGA-C8-A1HF-01Breastbreast invasive carcinomaFemale<65I/IIUnknownUnknownSD
NEDD4LSNVMissense_Mutationc.52N>Cp.Glu18Glnp.E18QQ96PU5protein_codingtolerated(0.33)benign(0.269)TCGA-C8-A1HM-01Breastbreast invasive carcinomaFemale>=65I/IIChemotherapydoxorubicinCR
NEDD4LSNVMissense_Mutationnovelc.2524N>Cp.Ile842Leup.I842LQ96PU5protein_codingtolerated(0.06)benign(0.02)TCGA-D8-A1XJ-01Breastbreast invasive carcinomaFemale>=65III/IVHormone TherapytamoxiphenSD
NEDD4LSNVMissense_Mutationnovelc.2524N>Gp.Ile842Valp.I842VQ96PU5protein_codingdeleterious(0.02)benign(0.038)TCGA-WT-AB41-01Breastbreast invasive carcinomaFemale<65I/IIChemotherapytaxotereCR
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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
23327NEDD4LENZYMEdiuretics18591455,21052022
23327NEDD4LENZYMEcitalopramCITALOPRAM23809733
23327NEDD4LENZYMEhydrochlorothiazideHYDROCHLOROTHIAZIDE18591455,21052022,19635985
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