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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Tissue samples summary

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Annotation details for different cell compartments

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Cell type statistics by disease state

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Cell type dynamics in malignant transformation

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Cell lineage trajectory inference

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TF regulatory network analysis

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Cell-cell interaction analysis

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Stemness, Senescence, Metaplasia and NeoTCR signature analysis

Tissue: Esophagus

Tissue samples summary

check button Cell type statistics by tissue samples.
EpitheliaImmuneStromal
Bar plot representation of the fraction of all Epithelial cells in each sample composed of each cell type for the integrated scRNA-seq datasets of Breast tissues. Each row represents a single sample, with each color representing a different cell type present in the sample.Bar plot representation of the fraction of all Immune cells in each sample composed of each cell type for the integrated scRNA-seq datasets of Breast tissues. Each row represents a single sample, with each color representing a different cell type present in the sample.Bar plot representation of the fraction of all Stromal cells in each sample composed of each cell type for the integrated scRNA-seq datasets of Breast tissues. Each row represents a single sample, with each color representing a different cell type present in the sample.
∗Bar plot representation of the fraction of all Epithelial, Immune and Stromal cells in each sample composed of each cell type for the integrated scRNA-seq datasets of Esophagus tissue. Each row represents a single sample, with each color representing a different cell type present in the sample.

check button Tissue summary table.
TissueDisease StateReplicatesEpithelia UMAPPMIDSourcePlatform
EsophagusADJLZE10DProjection

35536873

GSE199654

10X Genomics
EsophagusESCCLZE10TProjection

35536873

GSE199654

10X Genomics
EsophagusHGINLZE11DProjection

35536873

GSE199654

10X Genomics
EsophagusADJLZE11NProjection

35536873

GSE199654

10X Genomics
EsophagusESCCLZE11TProjection

35536873

GSE199654

10X Genomics
EsophagusHGINLZE1DProjection

35536873

GSE199654

10X Genomics
EsophagusESCCLZE1TProjection

35536873

GSE199654

10X Genomics
EsophagusHGINLZE2DProjection

35536873

GSE199654

10X Genomics
EsophagusADJLZE2NProjection

35536873

GSE199654

10X Genomics
EsophagusESCCLZE2TProjection

35536873

GSE199654

10X Genomics
EsophagusHGINLZE3DProjection

35536873

GSE199654

10X Genomics
EsophagusADJLZE3NProjection

35536873

GSE199654

10X Genomics
EsophagusESCCLZE3TProjection

35536873

GSE199654

10X Genomics
EsophagusHGINLZE4DProjection

35536873

GSE199654

10X Genomics
EsophagusADJLZE4NProjection

35536873

GSE199654

10X Genomics
EsophagusESCCLZE4TProjection

35536873

GSE199654

10X Genomics
EsophagusADJLZE5D1Projection

35536873

GSE199654

10X Genomics
EsophagusADJLZE5D2Projection

35536873

GSE199654

10X Genomics
EsophagusADJLZE5NProjection

35536873

GSE199654

10X Genomics
EsophagusESCCLZE5TProjection

35536873

GSE199654

10X Genomics
∗Projection of epithelial scRNA-seq cells from Esophagus diseased tissue samples into the manifold of normal tissue epithelial cells. Projected cells are colored by nearest normal cells in the projection and normal epithelial cells are colored gray.
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Annotation details for different cell compartments

check button Single-cell atlas of expresion.
UMAP representations and annotations of Epithelial cells in the integrated scRNA-seq data of the selected tissue.UMAP representations and annotations of Immune cells in the integrated scRNA-seq data of the selected tissue.UMAP representations and annotations of Stromal cells in the integrated scRNA-seq data of the selected tissue.
∗UMAP representations and annotations of Epithelial, Immune, Stromal cells in the integrated scRNA-seq data of Esophagus tissue. Colors represent cell types of each compartment.

check button Cell markers.
TissueMajor Cell TypeMinor Cell TypeFull NameMarkers
EsophagusEpiSTMStem-like cellsLGR5,SOX2,BMI1,KRT15,CD44,TP63,ABCG2,ALDH1A1
EsophagusEpiBASBasal cellsKRT5,KRT14,KRT15,TP63,ITGA6,ITGB4
EsophagusEpiGOBGobletAGR2,FOXA3,TFF3,HES6
EsophagusEpiQUIEQuiescent cellsDST,DLK2,KRT15
EsophagusEpiPROProliferating cellsHMGB2,TOP2A
EsophagusEpiKERKeratinocytesKRT5,KRT13,KRT14,KRT4,KRT18,KRT17,IVL
EsophagusEpiTRANSTransit-amplifying cellsDSP,SERPINB3
EsophagusEpiDIFFDifferentiated cellsTGM3,MT1G,RNASE7,KRT16,RNASE7
EsophagusImmNEUTNeutriphilsCEACAM3,FCGR3B,CXCR2
EsophagusImmMASTMast cellsTPSAB1,CPA3,HDC,CTSG,TPSB2,CMA1,MS4A2
EsophagusImmNKNatural killer cellsKLRF1,SH2D1B,NCAM1,FCGR3A,GNLY,NKG7,GZMH,FGFBP2,CX3CR1,NCR1,NCR3,B3GAT1
EsophagusImmMDSCMyeloid-derived suppressor cellsITGAM,LY6G6C,IL4R,ARG1
EsophagusImmM1MACM1 macrophagesFOLR2,FABP3,PLA2G2D,ITGAM,ITGAX,CSF1R,CD68,CD163,THBD
EsophagusImmINMONInflamotory monocytesCD14,CLEC9A,FCGR1A,LILRB2,CD209,CD1E,FCN1,VCAN,S100A8,S100A9
EsophagusImmM2MACM2 macrophagesCSF1R,CSF3R,MRC1,IL10,CCL18,VSIG4,CHI3L1
EsophagusImmBNNaive B cellsCD19,IGHD,IGLL1,CD27,CD38
EsophagusImmBMEMMemory B cellsPAX5,MS4A1,CD19,IGLL5,VPREB3,CD79A,CD79B,IGKC,CD74,HLA-DRA,CD37,CD22
EsophagusImmGCGerminal center B cellsSERPINA9,HRK,HTR3A,BCL6,CD180,FCRLA
EsophagusImmPLAPlasma cellsSSR4,IGLL5,IGLL1,AMPD1,IGHA1,IGHA2,JCHAIN,CD38,TNFRSF17,SDC1,IGHG1,MZB1
EsophagusImmTFHT follicular helperCXCR5,BCL6,ICA1,TOX,TOX2,IL6ST,MAGEH1,BTLA,ICOS,PDCD1,CD200
EsophagusImmTREGRegulatory T cellsBATF,TNFRSF4,FOXP3,CTLA4,LAIR2,IL2RA
EsophagusImmCD8TEXPProgenitor exhausted CD8+ T cellsPDCD1,IL7R,GPR183,NR4A3,REL,TCF7
EsophagusImmCD8TEXINTIntermediate exhausted CD8+ T cellsPDCD1,LAG3,CD101,CD38,CXCR6,TIGIT
EsophagusImmCD8TEREXTerminally exhausted CD8+ T cellsTOX,GZMB,ENTPD1,ITGAE,HAVCR2,CXCL13,PDCD1,LAYN,TOX,IFNG,GZMB,MIR155HG,TNFRSF9,ITGAE
EsophagusImmCD8TCMCentral memory CD8+ T cellsCCR7,SELL,IL7R,CD27,CD28,PRF1,GZMA,CCL5,GPR183,S1PR1
EsophagusImmCD8TRMCD8+ tissue resident memory T cellsCD6,XCL1,XCL2,MYADM,CAPG,RORA,NR4A1,NR4A2,NR4A3,CD69,ITGAE
EsophagusStrENDEndothelial cellsPECAM1,PLVAP,VWF,CLDN5,FLT1,RAMP2,FAM110D,INHBB,NPR1,NOVA2,GPIHBP1,SOX17
EsophagusStrLYMENDLymphatic endothelial cellsPROX1,LYVE1,PDPN,PROCR,FLT4
EsophagusStrMSCMesenchymal stem cellsNT5E,THY1,ENG,CD44,ITGB1,MCAM,ENDOD1
EsophagusStrFIBFibroblastsBMP7,MAP3K2,COL6A1,CD36,CD44,CBLN2,SPOCK1,ACSS3,FN1,COL3A1,BGN,DCN,POSTN,C1R,MMP2,FGF7,MME,CD47
EsophagusStrSMCSmooth muscle cellsACTA2,CNN1,MYH11,TAGLN,CALD1,TAGLN2
EsophagusStrPERIPericytesPDGFRA,CSPG4,RGS5,MCAM,COX4I2,KCNJ8,HIGD1B,NOTCH3,HEYL,FAM162B
EsophagusStrPVAPost capillary venulesSELP,ZNF385D,FAM155A,GALNT15,MADCAM1,CORT
EsophagusStrMVAMicrovascular cellsPLVAP,CD36,DYSF,NRP1,SH3BP5,EXOC3L2,FABP5,VWA1,BAALC,PRSS23,RAPGEF4,APLN,HTRA1
EsophagusStrECMExtracellular matrixFBLN1,PCOLCE2,MFAP5
EsophagusStrINCAFIntermediate cancer-associated fibroblastsPDGFRA,POSTN,ID1,ID3
EsophagusStrICAFInflammatory cancer-associated fibroblastsTWIST1,WNT2,FAP,CXCL1,CXCL2,CYR61,IL1B,IL6,HGF

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Cell type statistics by disease state

Stacked bar graph representation of the fraction of each epithelial cell type derived from samples with different Disease States in the integrated dataset of the selected tissue. Cells from each Disease State sample have a different color.Stacked bar graph representation of the fraction of each immune cell type derived from samples with different Disease States in the integrated dataset of the selected tissue. Cells from each Disease State sample have a different color.Stacked bar graph representation of the fraction of each stromal cell type derived from samples with different Disease States in the integrated dataset of the selected tissue. Cells from each Disease State sample have a different color.
∗Stacked bar graph representation of the fraction of each epithelial cell type derived from samples with different Disease States in the integrated dataset of Esophagus tissue. Cells from each Disease State sample have a different color.

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Cell type dynamics in malignant transformation

Fraction of cell type in each scRNA-seq sample plotted against position of the sample in the malignancy continuum for all cell types in the selected tissue. Samples are colored based on if they are derived from different Disease States.Fraction of cell type in each scRNA-seq sample plotted against position of the sample in the malignancy continuum for all cell types in the selected tissue. Samples are colored based on if they are derived from different Disease States.Fraction of cell type in each scRNA-seq sample plotted against position of the sample in the malignancy continuum for all cell types in the selected tissue. Samples are colored based on if they are derived from different Disease States.
Fraction of cell type in each scRNA-seq sample plotted against position of the sample in the malignancy continuum for all cell types in the selected tissue. Samples are colored based on if they are derived from different Disease States.Fraction of cell type in each scRNA-seq sample plotted against position of the sample in the malignancy continuum for all cell types in the selected tissue. Samples are colored based on if they are derived from different Disease States.Fraction of cell type in each scRNA-seq sample plotted against position of the sample in the malignancy continuum for all cell types in the selected tissue. Samples are colored based on if they are derived from different Disease States.
Fraction of cell type in each scRNA-seq sample plotted against position of the sample in the malignancy continuum for all cell types in the selected tissue. Samples are colored based on if they are derived from different Disease States.Fraction of cell type in each scRNA-seq sample plotted against position of the sample in the malignancy continuum for all cell types in the selected tissue. Samples are colored based on if they are derived from different Disease States.Fraction of cell type in each scRNA-seq sample plotted against position of the sample in the malignancy continuum for all cell types in the selected tissue. Samples are colored based on if they are derived from different Disease States.
Fraction of cell type in each scRNA-seq sample plotted against position of the sample in the malignancy continuum for all cell types in the selected tissue. Samples are colored based on if they are derived from different Disease States.Fraction of cell type in each scRNA-seq sample plotted against position of the sample in the malignancy continuum for all cell types in the selected tissue. Samples are colored based on if they are derived from different Disease States.Fraction of cell type in each scRNA-seq sample plotted against position of the sample in the malignancy continuum for all cell types in the selected tissue. Samples are colored based on if they are derived from different Disease States.
Fraction of cell type in each scRNA-seq sample plotted against position of the sample in the malignancy continuum for all cell types in the selected tissue. Samples are colored based on if they are derived from different Disease States.Fraction of cell type in each scRNA-seq sample plotted against position of the sample in the malignancy continuum for all cell types in the selected tissue. Samples are colored based on if they are derived from different Disease States.Fraction of cell type in each scRNA-seq sample plotted against position of the sample in the malignancy continuum for all cell types in the selected tissue. Samples are colored based on if they are derived from different Disease States.
Fraction of cell type in each scRNA-seq sample plotted against position of the sample in the malignancy continuum for all cell types in the selected tissue. Samples are colored based on if they are derived from different Disease States.Fraction of cell type in each scRNA-seq sample plotted against position of the sample in the malignancy continuum for all cell types in the selected tissue. Samples are colored based on if they are derived from different Disease States.Fraction of cell type in each scRNA-seq sample plotted against position of the sample in the malignancy continuum for all cell types in the selected tissue. Samples are colored based on if they are derived from different Disease States.
∗Fraction of cell type in each scRNA-seq sample plotted against position of the sample in the malignancy continuum for all cell types in Esophagus tissue. Samples are colored based on if they are derived from different Disease States. Cell fractions are computed by dividing the number of cells of a given cell type by the total number of cells in the compartment (epithelial versus immune versus stromal).
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Cell lineage trajectory inference

Disease StateEpitheliaImmuneStromal
∗RNA velocity maps for epithelial, immune and stromal compartments of Esophagus tissue with different disease states.

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TF regulatory network analysis

Disease StateEpitheliaImmuneStromal
HealthyHeatmap representation of significantly different TFs among all cell types of epithelial compartment in Healthy-derived samples of Esophagus tissue by comparing their average AUC by using pySCENIC in Python.Heatmap representation of significantly different TFs among all cell types of immune compartment in Healthy-derived samples of Esophagus tissue by comparing their average AUC by using pySCENIC in Python.Heatmap representation of significantly different TFs among all cell types of stromal compartment in Healthy-derived samples of Esophagus tissue by comparing their average AUC by using pySCENIC in Python.
TF target networkTF target networkTF target network
ADJHeatmap representation of significantly different TFs among all cell types of epithelial compartment in ADJ-derived samples of Esophagus tissue by comparing their average AUC by using pySCENIC in Python.Heatmap representation of significantly different TFs among all cell types of immune compartment in ADJ-derived samples of Esophagus tissue by comparing their average AUC by using pySCENIC in Python.Heatmap representation of significantly different TFs among all cell types of stromal compartment in ADJ-derived samples of Esophagus tissue by comparing their average AUC by using pySCENIC in Python.
TF target networkTF target networkTF target network
PrecancerHeatmap representation of significantly different TFs among all cell types of epithelial compartment in Precancer-derived samples of Esophagus tissue by comparing their average AUC by using pySCENIC in Python.There is no Precancer regulation activityThere is no Precancer regulation activity
TF target network
ESCCHeatmap representation of significantly different TFs among all cell types of epithelial compartment in ESCC-derived samples of Esophagus tissue by comparing their average AUC by using pySCENIC in Python.Heatmap representation of significantly different TFs among all cell types of immune compartment in ESCC-derived samples of Esophagus tissue by comparing their average AUC by using pySCENIC in Python.Heatmap representation of significantly different TFs among all cell types of stromal compartment in ESCC-derived samples of Esophagus tissue by comparing their average AUC by using pySCENIC in Python.
TF target networkTF target networkTF target network
∗Heatmap: Heatmap representation of significantly different TFs among all cell types of epithelial compartment in Healthy-derived samples of Esophagus tissue by comparing their average AUC by using pySCENIC in Python. Regulon specific score for each cell type is colored.
∗Network: TF target network created from Healthy-derived samples of Esophagus tissue using Top 50 predicted target genes of each regulon. Edge lengths are the inferred TF-target weightings.

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Cell-cell interaction analysis

Disease StateCell TypeCircleSourceTarget
HealthyDIFFThe cell-cell communications between each two interacting cell types in Healthy-derived samples of the selected tissue. Different colors in the circle plot represent different cell groups and the edge width is proportional to the indicated number of ligand-receptor pairs.Bubble plot of proportion to the communication probability in significant signaling pathways between this cell type and its source cell population in Healthy-derived samples of the selected tissue. Each row represents the significant ligand and receptor gene pairs.Bubble plot of proportion to the communication probability in significant signaling pathways between this cell type and its target cell population in Healthy-derived samples of the selected tissue. Each row represents the significant ligand and receptor gene pairs.
ECMThe cell-cell communications between each two interacting cell types in Healthy-derived samples of the selected tissue. Different colors in the circle plot represent different cell groups and the edge width is proportional to the indicated number of ligand-receptor pairs.Bubble plot of proportion to the communication probability in significant signaling pathways between this cell type and its source cell population in Healthy-derived samples of the selected tissue. Each row represents the significant ligand and receptor gene pairs.Bubble plot of proportion to the communication probability in significant signaling pathways between this cell type and its target cell population in Healthy-derived samples of the selected tissue. Each row represents the significant ligand and receptor gene pairs.
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Disease StateCell TypeCircleSourceTarget
ADJGOBThe cell-cell communications between each two interacting cell types in ADJ-derived samples of the selected tissue. Different colors in the circle plot represent different cell groups and the edge width is proportional to the indicated number of ligand-receptor pairs. Bubble plot of proportion to the communication probability in significant signaling pathways between this cell type and its source cell population in ADJ-derived samples of the selected tissue. Each row represents the significant ligand and receptor gene pairs.Bubble plot of proportion to the communication probability in significant signaling pathways between this cell type and its target cell population in ADJ-derived samples of the selected tissue. Each row represents the significant ligand and receptor gene pairs.
KERThe cell-cell communications between each two interacting cell types in ADJ-derived samples of the selected tissue. Different colors in the circle plot represent different cell groups and the edge width is proportional to the indicated number of ligand-receptor pairs. Bubble plot of proportion to the communication probability in significant signaling pathways between this cell type and its source cell population in ADJ-derived samples of the selected tissue. Each row represents the significant ligand and receptor gene pairs.Bubble plot of proportion to the communication probability in significant signaling pathways between this cell type and its target cell population in ADJ-derived samples of the selected tissue. Each row represents the significant ligand and receptor gene pairs.
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Disease StateCell TypeCircleSourceTarget
PrecancerKERThe cell-cell communications between each two interacting cell types in Precancer-derived samples of the selected tissue. Different colors in the circle plot represent different cell groups and the edge width is proportional to the indicated number of ligand-receptor pairs. Bubble plot of proportion to the communication probability in significant signaling pathways between this cell type and its source cell population in Precancer-derived samples of the selected tissue. Each row represents the significant ligand and receptor gene pairs.Bubble plot of proportion to the communication probability in significant signaling pathways between this cell type and its target cell population in Precancer-derived samples of the selected tissue. Each row represents the significant ligand and receptor gene pairs.
PROThe cell-cell communications between each two interacting cell types in Precancer-derived samples of the selected tissue. Different colors in the circle plot represent different cell groups and the edge width is proportional to the indicated number of ligand-receptor pairs. Bubble plot of proportion to the communication probability in significant signaling pathways between this cell type and its source cell population in Precancer-derived samples of the selected tissue. Each row represents the significant ligand and receptor gene pairs.Bubble plot of proportion to the communication probability in significant signaling pathways between this cell type and its target cell population in Precancer-derived samples of the selected tissue. Each row represents the significant ligand and receptor gene pairs.
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Disease StateCell TypeCircleSourceTarget
ESCCBMEMThe cell-cell communications between each two interacting cell types in ESCC-derived samples of Esophagus tissue. Different colors in the circle plot represent different cell groups and the edge width is proportional to the indicated number of ligand-receptor pairs.Bubble plot of proportion to the communication probability in significant signaling pathways between this cell type and its source cell population in ESCC-derived samples of Esophagus tissue. Each row represents the significant ligand and receptor gene pairs.Bubble plot of proportion to the communication probability in significant signaling pathways between this cell type and its target cell population in ESCC-derived samples of Esophagus tissue. Each row represents the significant ligand and receptor gene pairs.
BNThe cell-cell communications between each two interacting cell types in ESCC-derived samples of Esophagus tissue. Different colors in the circle plot represent different cell groups and the edge width is proportional to the indicated number of ligand-receptor pairs.Bubble plot of proportion to the communication probability in significant signaling pathways between this cell type and its source cell population in ESCC-derived samples of Esophagus tissue. Each row represents the significant ligand and receptor gene pairs.Bubble plot of proportion to the communication probability in significant signaling pathways between this cell type and its target cell population in ESCC-derived samples of Esophagus tissue. Each row represents the significant ligand and receptor gene pairs.
∗The cell-cell communications between each two interacting cell types in different states-derived samples of Esophagus tissue. Different colors in the circle plot represent different cell groups and the edge width is proportional to the indicated number of ligand-receptor pairs.
∗Bubble plot of proportion to the communication probability in significant signaling pathways between this cell type and its source and target cell population. Each row represents the significant ligand and receptor gene pairs.
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Stemness, Senescence, Metaplasia and NeoTCR signature analysis

check button Developmental potential inference using CytoTRACE.
1_developmental_potential_in_Healthy.png shows the analysis results of stemness, senescence, and metaplasia signatures2_developmental_potential_in_Precancer.png shows the analysis results of stemness, senescence, and metaplasia signatures3_developmental_potential_in_ESCC.png shows the analysis results of stemness, senescence, and metaplasia signatures
∗Ridge plots of CytoTRACE score distributions for epithelial cells.

check button Cellular senescence signature (for three compartments).
Disease StateEpitheliaImmuneStromal
HealthyComparisons for degree of cellular senescence of epithelial compartment in Healthy-derived samples of Esophagus tissue.Comparisons for degree of cellular senescence of immune compartment in Healthy-derived samples of Esophagus tissue.Comparisons for degree of cellular senescence of stromal compartment in Healthy-derived samples of Esophagus tissue.
PrecancerComparisons for degree of cellular senescence of epithelial compartment in Precancer-derived samples of Esophagus tissue.There is no Precancer comparisons for degree of cellular senescenceThere is no Precancer comparisons for degree of cellular senescence
ESCCComparisons for degree of cellular senescence of epithelial compartment in ESCC-derived samples of Esophagus tissue.Comparisons for degree of cellular senescence of immune compartment in ESCC-derived samples of Esophagus tissue.Comparisons for degree of cellular senescence of stromal compartment in ESCC-derived samples of Esophagus tissue.
∗Comparisons for degree of cellular senescence among epithelial, immune and stromal cell populations of Esophagus tissue with different disease states.

check button Metaplasia and damage response signature (for epithelial cells).
HealthyPrecancerCC
Comparisons of Metaplasia-associated damage scores among epithelial cell subpopulations.Comparisons of Metaplasia-associated damage scores among epithelial cell subpopulations.Comparisons of Metaplasia-associated damage scores among epithelial cell subpopulations.
∗Comparisons of Metaplasia-associated damage scores among epithelial cell subpopulations.

check button Neoantigen-specific TCR clonotypes (NeoTCR) signature.
Comparisons of CD4+ and CD8+ NeoTCR signature scores among different disease states.Comparisons of CD4+ and CD8+ NeoTCR signature scores among different disease states.
∗Comparisons of CD4+ and CD8+ NeoTCR signature scores among different disease states.