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: POLE4

Gene summary for POLE4

check button Gene summary.

Gene informationSpeciesHuman
Gene symbol

POLE4

Gene ID

56655

Gene nameDNA polymerase epsilon 4, accessory subunit
Gene AliasYHHQ1
Cytomap2p12
Gene Typeprotein-coding
GO ID

GO:0006139

UniProtAcc

Q9NR33


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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
56655POLE4HTA11_2487_2000001011HumanColorectumSER4.76e-041.92e-01-0.1808
56655POLE4HTA11_1938_2000001011HumanColorectumAD3.59e-073.42e-01-0.0811
56655POLE4HTA11_347_2000001011HumanColorectumAD3.77e-092.37e-01-0.1954
56655POLE4HTA11_411_2000001011HumanColorectumSER4.02e-033.54e-01-0.2602
56655POLE4HTA11_3361_2000001011HumanColorectumAD1.74e-032.18e-01-0.1207
56655POLE4HTA11_83_2000001011HumanColorectumSER4.54e-083.58e-01-0.1526
56655POLE4HTA11_696_2000001011HumanColorectumAD1.26e-032.34e-01-0.1464
56655POLE4HTA11_1391_2000001011HumanColorectumAD1.07e-082.99e-01-0.059
56655POLE4HTA11_2992_2000001011HumanColorectumSER5.70e-032.84e-01-0.1706
56655POLE4HTA11_546_2000001011HumanColorectumAD7.09e-053.11e-01-0.0842
56655POLE4HTA11_866_3004761011HumanColorectumAD1.77e-031.56e-010.096
56655POLE4HTA11_7696_3000711011HumanColorectumAD1.61e-022.09e-010.0674
56655POLE4HTA11_6818_2000001021HumanColorectumAD1.03e-021.69e-010.0588
56655POLE4HTA11_99999970781_79442HumanColorectumMSS1.74e-032.24e-010.294
56655POLE4HTA11_99999973899_84307HumanColorectumMSS1.84e-023.11e-010.2585
56655POLE4HTA11_99999974143_84620HumanColorectumMSS2.79e-062.65e-010.3005
56655POLE4LZE2DHumanEsophagusHGIN1.27e-024.47e-010.0642
56655POLE4LZE2THumanEsophagusESCC3.22e-039.46e-010.082
56655POLE4LZE4THumanEsophagusESCC5.23e-174.52e-010.0811
56655POLE4LZE5THumanEsophagusESCC1.54e-034.67e-010.0514
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check button Transcriptomic changes along malignancy continuum.
TissueExpression DynamicsAbbreviation
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
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
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
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:0071897ColorectumADDNA biosynthetic process55/3918180/187231.46e-031.24e-0255
GO:00718971ColorectumSERDNA biosynthetic process43/2897180/187231.99e-031.98e-0243
GO:00718972ColorectumMSSDNA biosynthetic process50/3467180/187231.45e-031.35e-0250
GO:007189710EsophagusHGINDNA biosynthetic process44/2587180/187238.97e-051.96e-0344
GO:007189716EsophagusESCCDNA biosynthetic process127/8552180/187231.04e-113.85e-10127
GO:00718975LiverHCCDNA biosynthetic process99/7958180/187234.66e-043.08e-0399
GO:00718979Oral cavityOSCCDNA biosynthetic process106/7305180/187234.86e-088.95e-07106
GO:007189715Oral cavityLPDNA biosynthetic process71/4623180/187238.04e-061.52e-0471
GO:007189718SkincSCCDNA biosynthetic process74/4864180/187236.33e-068.92e-0574
GO:0071897110ThyroidPTCDNA biosynthetic process82/5968180/187237.98e-056.81e-0482
GO:007189723ThyroidATCDNA biosynthetic process91/6293180/187231.84e-062.24e-0591
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check button Enriched KEGG pathways.
Pathway IDTissueDisease StageDescriptionGene RatioBg Ratiopvaluep.adjustqvalueCount
hsa034205EsophagusHGINNucleotide excision repair29/138363/84652.96e-085.36e-074.26e-0729
hsa0342012EsophagusHGINNucleotide excision repair29/138363/84652.96e-085.36e-074.26e-0729
hsa0342022EsophagusESCCNucleotide excision repair54/420563/84652.01e-092.17e-081.11e-0854
hsa034104EsophagusESCCBase excision repair38/420544/84653.59e-072.62e-061.34e-0638
hsa030304EsophagusESCCDNA replication32/420536/84657.71e-075.06e-062.59e-0632
hsa0342032EsophagusESCCNucleotide excision repair54/420563/84652.01e-092.17e-081.11e-0854
hsa0341011EsophagusESCCBase excision repair38/420544/84653.59e-072.62e-061.34e-0638
hsa0303011EsophagusESCCDNA replication32/420536/84657.71e-075.06e-062.59e-0632
hsa03420LiverCirrhoticNucleotide excision repair29/253063/84654.81e-031.74e-021.07e-0229
hsa034201LiverCirrhoticNucleotide excision repair29/253063/84654.81e-031.74e-021.07e-0229
hsa034202LiverHCCNucleotide excision repair41/402063/84653.59e-031.12e-026.22e-0341
hsa034203LiverHCCNucleotide excision repair41/402063/84653.59e-031.12e-026.22e-0341
hsa034204Oral cavityOSCCNucleotide excision repair49/370463/84653.48e-082.91e-071.48e-0749
hsa03030Oral cavityOSCCDNA replication31/370436/84651.70e-071.19e-066.03e-0731
hsa03410Oral cavityOSCCBase excision repair32/370444/84659.11e-053.25e-041.65e-0432
hsa0342011Oral cavityOSCCNucleotide excision repair49/370463/84653.48e-082.91e-071.48e-0749
hsa030301Oral cavityOSCCDNA replication31/370436/84651.70e-071.19e-066.03e-0731
hsa034101Oral cavityOSCCBase excision repair32/370444/84659.11e-053.25e-041.65e-0432
hsa0342021Oral cavityLPNucleotide excision repair37/241863/84655.14e-076.33e-064.08e-0637
hsa030302Oral cavityLPDNA replication23/241836/84651.08e-057.79e-055.02e-0523
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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
POLE4MLUMBreastDCISCOX6A1,UQCR11,RPS26, etc.6.44e-01The 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.
POLE4TACColorectumHealthyCXXC1,KRT18,CST3, etc.5.94e-02The 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.
POLE4ABSColorectumHealthyCXXC1,KRT18,CST3, etc.3.56e-01The 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.
POLE4ASCColorectumHealthyCXXC1,KRT18,CST3, etc.1.15e-01The 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.
POLE4STMColorectumHealthyCXXC1,KRT18,CST3, etc.1.41e-01The 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.
POLE4MONLiverCirrhoticS100A9,S100A8,CSTA, etc.4.91e-01The 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.
POLE4MONLiverHCCS100A9,S100A8,CSTA, etc.2.56e-02The 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.
POLE4PVALiverCirrhoticLOX,CCL14,ZNF784, etc.4.18e-01The 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.
POLE4SECLiverHealthyLOX,CCL14,ZNF784, etc.7.14e-01The 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.
POLE4ALVMACLungADJS100A8,S100A9,S100A12, etc.1.29e-01The 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.
∗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
POLE4SNVMissense_Mutationnovelc.202G>Ap.Ala68Thrp.A68TQ9NR33protein_codingtolerated(0.29)benign(0.078)TCGA-AX-A2HA-01Endometriumuterine corpus endometrioid carcinomaFemale<65I/IIUnknownUnknownSD
POLE4SNVMissense_Mutationnovelc.272N>Tp.Arg91Metp.R91MQ9NR33protein_codingdeleterious(0)probably_damaging(1)TCGA-B5-A3FA-01Endometriumuterine corpus endometrioid carcinomaFemale>=65I/IIUnknownUnknownSD
POLE4SNVMissense_Mutationrs199691810c.307N>Gp.Ile103Valp.I103VQ9NR33protein_codingtolerated(0.1)benign(0.325)TCGA-34-5234-01Lunglung squamous cell carcinomaFemale>=65I/IIUnknownUnknownSD
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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
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