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: ISG15

Gene summary for ISG15

check button Gene summary.

Gene informationSpeciesHuman
Gene symbol

ISG15

Gene ID

9636

Gene nameISG15 ubiquitin like modifier
Gene AliasG1P2
Cytomap1p36.33
Gene Typeprotein-coding
GO ID

GO:0001503

UniProtAcc

P05161


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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
9636ISG15GSM4909281HumanBreastIDC1.76e-509.58e-010.21
9636ISG15GSM4909285HumanBreastIDC1.02e-135.85e-010.21
9636ISG15GSM4909286HumanBreastIDC2.74e-03-1.84e-010.1081
9636ISG15GSM4909287HumanBreastIDC5.25e-146.08e-010.2057
9636ISG15GSM4909288HumanBreastIDC2.15e-151.01e+000.0988
9636ISG15GSM4909290HumanBreastIDC1.22e-095.22e-010.2096
9636ISG15GSM4909294HumanBreastIDC3.33e-033.21e-010.2022
9636ISG15GSM4909297HumanBreastIDC1.09e-072.77e-010.1517
9636ISG15GSM4909301HumanBreastIDC2.89e-052.90e-010.1577
9636ISG15GSM4909304HumanBreastIDC4.02e-032.61e-010.1636
9636ISG15GSM4909307HumanBreastIDC3.39e-681.26e+000.1569
9636ISG15GSM4909308HumanBreastIDC7.77e-811.38e+000.158
9636ISG15GSM4909309HumanBreastIDC6.18e-381.10e+000.0483
9636ISG15GSM4909311HumanBreastIDC8.44e-05-1.49e-010.1534
9636ISG15GSM4909312HumanBreastIDC9.54e-03-1.54e-010.1552
9636ISG15GSM4909315HumanBreastIDC1.17e-073.60e-010.21
9636ISG15GSM4909317HumanBreastIDC3.66e-186.46e-010.1355
9636ISG15GSM4909318HumanBreastIDC1.25e-067.90e-010.2031
9636ISG15GSM4909319HumanBreastIDC1.10e-111.07e-010.1563
9636ISG15GSM4909320HumanBreastIDC4.15e-159.17e-010.1575
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check button Transcriptomic changes along malignancy continuum.
TissueExpression DynamicsAbbreviation
BreastThe 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.IDC: Invasive ductal carcinoma
DCIS: Ductal carcinoma in situ
Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
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
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:00160329BreastPrecancerviral process58/1080415/187233.42e-103.16e-0858
GO:00190589BreastPrecancerviral life cycle47/1080317/187232.42e-091.99e-0747
GO:19033209BreastPrecancerregulation of protein modification by small protein conjugation or removal38/1080242/187231.71e-081.17e-0638
GO:19033219BreastPrecancernegative regulation of protein modification by small protein conjugation or removal21/108095/187238.09e-084.61e-0621
GO:00313969BreastPrecancerregulation of protein ubiquitination33/1080210/187231.45e-077.82e-0633
GO:00313979BreastPrecancernegative regulation of protein ubiquitination19/108083/187231.85e-079.54e-0619
GO:00022629BreastPrecancermyeloid cell homeostasis27/1080157/187233.10e-071.49e-0527
GO:00507929BreastPrecancerregulation of viral process27/1080164/187237.59e-073.05e-0527
GO:00341019BreastPrecancererythrocyte homeostasis23/1080129/187231.20e-064.60e-0523
GO:00432549BreastPrecancerregulation of protein-containing complex assembly50/1080428/187231.63e-065.97e-0550
GO:00313349BreastPrecancerpositive regulation of protein-containing complex assembly33/1080237/187232.39e-068.21e-0533
GO:00300999BreastPrecancermyeloid cell differentiation45/1080381/187234.00e-061.25e-0445
GO:00018196BreastPrecancerpositive regulation of cytokine production52/1080467/187234.18e-061.29e-0452
GO:00190799BreastPrecancerviral genome replication22/1080131/187235.63e-061.66e-0422
GO:00705858BreastPrecancerprotein localization to mitochondrion21/1080125/187239.07e-062.42e-0421
GO:19039009BreastPrecancerregulation of viral life cycle23/1080148/187231.31e-053.30e-0423
GO:00456379BreastPrecancerregulation of myeloid cell differentiation28/1080210/187233.05e-056.72e-0428
GO:19037069BreastPrecancerregulation of hemopoiesis41/1080367/187233.95e-058.52e-0441
GO:00488729BreastPrecancerhomeostasis of number of cells32/1080272/187231.03e-041.89e-0332
GO:00302189BreastPrecancererythrocyte differentiation18/1080120/187231.76e-042.87e-0318
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check button Enriched KEGG pathways.
Pathway IDTissueDisease StageDescriptionGene RatioBg Ratiopvaluep.adjustqvalueCount
hsa0517118BreastPrecancerCoronavirus disease - COVID-1981/684232/84653.74e-322.36e-301.81e-3081
hsa0516918BreastPrecancerEpstein-Barr virus infection35/684202/84651.15e-051.26e-049.64e-0535
hsa0517119BreastPrecancerCoronavirus disease - COVID-1981/684232/84653.74e-322.36e-301.81e-3081
hsa0516919BreastPrecancerEpstein-Barr virus infection35/684202/84651.15e-051.26e-049.64e-0535
hsa0517124BreastIDCCoronavirus disease - COVID-1986/867232/84651.50e-289.72e-277.27e-2786
hsa0516922BreastIDCEpstein-Barr virus infection45/867202/84653.16e-076.05e-064.52e-0645
hsa0517134BreastIDCCoronavirus disease - COVID-1986/867232/84651.50e-289.72e-277.27e-2786
hsa0516932BreastIDCEpstein-Barr virus infection45/867202/84653.16e-076.05e-064.52e-0645
hsa0517144BreastDCISCoronavirus disease - COVID-1986/846232/84652.42e-291.56e-271.15e-2786
hsa0516941BreastDCISEpstein-Barr virus infection46/846202/84655.60e-081.13e-068.33e-0746
hsa0517154BreastDCISCoronavirus disease - COVID-1986/846232/84652.42e-291.56e-271.15e-2786
hsa0516951BreastDCISEpstein-Barr virus infection46/846202/84655.60e-081.13e-068.33e-0746
hsa0517120CervixCCCoronavirus disease - COVID-19111/1267232/84651.82e-335.90e-313.49e-31111
hsa0516920CervixCCEpstein-Barr virus infection57/1267202/84657.30e-077.39e-064.37e-0657
hsa051657CervixCCHuman papillomavirus infection74/1267331/84651.70e-041.02e-036.03e-0474
hsa05171110CervixCCCoronavirus disease - COVID-19111/1267232/84651.82e-335.90e-313.49e-31111
hsa05169110CervixCCEpstein-Barr virus infection57/1267202/84657.30e-077.39e-064.37e-0657
hsa0516512CervixCCHuman papillomavirus infection74/1267331/84651.70e-041.02e-036.03e-0474
hsa0517125CervixHSIL_HPVCoronavirus disease - COVID-1991/459232/84652.14e-563.13e-542.53e-5491
hsa0516923CervixHSIL_HPVEpstein-Barr virus infection22/459202/84651.35e-039.68e-037.82e-0322
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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
ISG15SNVMissense_Mutationrs752866829c.109N>Ap.Gly37Serp.G37SP05161protein_codingdeleterious(0.04)benign(0.283)TCGA-AD-A5EJ-01Colorectumcolon adenocarcinomaFemale>=65I/IIUnknownUnknownSD
ISG15SNVMissense_Mutationc.131N>Tp.Arg44Leup.R44LP05161protein_codingtolerated(0.06)benign(0.123)TCGA-D5-6920-01Colorectumcolon adenocarcinomaFemale>=65I/IIUnknownUnknownSD
ISG15SNVMissense_Mutationrs368865539c.275N>Ap.Arg92Hisp.R92HP05161protein_codingtolerated(0.13)benign(0.115)TCGA-AP-A1DK-01Endometriumuterine corpus endometrioid carcinomaFemale<65I/IIUnknownUnknownSD
ISG15SNVMissense_Mutationc.178N>Ap.Leu60Ilep.L60IP05161protein_codingdeleterious(0.01)probably_damaging(0.999)TCGA-BS-A0UL-01Endometriumuterine corpus endometrioid carcinomaFemale<65I/IIUnknownUnknownSD
ISG15SNVMissense_Mutationrs148041041c.131N>Ap.Arg44Hisp.R44HP05161protein_codingtolerated(0.1)probably_damaging(0.952)TCGA-EC-A24G-01Endometriumuterine corpus endometrioid carcinomaFemale<65I/IIChemotherapydoxorubicinSD
ISG15deletionFrame_Shift_Delnovelc.411delNp.Glu139SerfsTer7p.E139Sfs*7P05161protein_codingTCGA-SL-A6JA-01Endometriumuterine corpus endometrioid carcinomaFemale>=65I/IIUnknownUnknownSD
ISG15SNVMissense_Mutationnovelc.464G>Tp.Arg155Leup.R155LP05161protein_codingdeleterious(0)probably_damaging(0.949)TCGA-55-6981-01Lunglung adenocarcinomaFemale<65III/IVChemotherapychemoCR
ISG15SNVMissense_Mutationrs748078443c.202G>Ap.Gly68Serp.G68SP05161protein_codingtolerated(0.14)possibly_damaging(0.588)TCGA-34-5928-01Lunglung 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
9636ISG15ENZYME, DRUGGABLE GENOMEinhibitorIRINOTECANIRINOTECAN
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