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Gene: MAP4K4 |
Gene summary for MAP4K4 |
 Gene summary. |
| Gene information | Species | Human | Gene symbol | MAP4K4 | Gene ID | 9448 |
| Gene name | mitogen-activated protein kinase kinase kinase kinase 4 | |
| Gene Alias | FLH21957 | |
| Cytomap | 2q11.2 | |
| Gene Type | protein-coding | GO ID | GO:0000165 | UniProtAcc | O95819 |
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Malignant transformation analysis |
| 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 |
| Malignant transformation involving gene list. |
| Entrez ID | Symbol | Replicates | Species | Organ | Tissue | Adj P-value | Log2FC | Malignancy |
| 9448 | MAP4K4 | LZE2T | Human | Esophagus | ESCC | 5.45e-08 | 9.26e-01 | 0.082 |
| 9448 | MAP4K4 | LZE4T | Human | Esophagus | ESCC | 1.90e-14 | 1.01e-01 | 0.0811 |
| 9448 | MAP4K4 | LZE7T | Human | Esophagus | ESCC | 6.00e-09 | 5.96e-01 | 0.0667 |
| 9448 | MAP4K4 | LZE22T | Human | Esophagus | ESCC | 2.98e-03 | 3.74e-01 | 0.068 |
| 9448 | MAP4K4 | LZE24T | Human | Esophagus | ESCC | 1.31e-12 | 1.70e-01 | 0.0596 |
| 9448 | MAP4K4 | LZE6T | Human | Esophagus | ESCC | 2.12e-03 | 1.10e-01 | 0.0845 |
| 9448 | MAP4K4 | P2T-E | Human | Esophagus | ESCC | 1.75e-14 | 2.93e-01 | 0.1177 |
| 9448 | MAP4K4 | P4T-E | Human | Esophagus | ESCC | 1.09e-18 | 4.98e-01 | 0.1323 |
| 9448 | MAP4K4 | P5T-E | Human | Esophagus | ESCC | 1.79e-20 | 2.41e-01 | 0.1327 |
| 9448 | MAP4K4 | P8T-E | Human | Esophagus | ESCC | 3.31e-23 | 2.34e-01 | 0.0889 |
| 9448 | MAP4K4 | P9T-E | Human | Esophagus | ESCC | 2.70e-17 | 5.34e-01 | 0.1131 |
| 9448 | MAP4K4 | P10T-E | Human | Esophagus | ESCC | 5.54e-41 | 7.78e-01 | 0.116 |
| 9448 | MAP4K4 | P11T-E | Human | Esophagus | ESCC | 4.03e-11 | 4.21e-01 | 0.1426 |
| 9448 | MAP4K4 | P12T-E | Human | Esophagus | ESCC | 1.64e-14 | 3.33e-01 | 0.1122 |
| 9448 | MAP4K4 | P15T-E | Human | Esophagus | ESCC | 6.75e-14 | 5.09e-01 | 0.1149 |
| 9448 | MAP4K4 | P16T-E | Human | Esophagus | ESCC | 2.64e-15 | 2.47e-01 | 0.1153 |
| 9448 | MAP4K4 | P17T-E | Human | Esophagus | ESCC | 9.37e-09 | 2.46e-01 | 0.1278 |
| 9448 | MAP4K4 | P19T-E | Human | Esophagus | ESCC | 3.83e-06 | 7.37e-01 | 0.1662 |
| 9448 | MAP4K4 | P21T-E | Human | Esophagus | ESCC | 1.17e-33 | 6.90e-01 | 0.1617 |
| 9448 | MAP4K4 | P22T-E | Human | Esophagus | ESCC | 8.00e-28 | 3.64e-01 | 0.1236 |
| Page: 1 2 3 4 5 6 7 8 |
| Transcriptomic changes along malignancy continuum. |
| Tissue | Expression Dynamics | Abbreviation |
| Esophagus |  | ESCC: Esophageal squamous cell carcinoma |
| HGIN: High-grade intraepithelial neoplasias | ||
| LGIN: Low-grade intraepithelial neoplasias | ||
| Liver |  | HCC: Hepatocellular carcinoma |
| NAFLD: Non-alcoholic fatty liver disease | ||
| Lung |  | AAH: Atypical adenomatous hyperplasia |
| AIS: Adenocarcinoma in situ | ||
| IAC: Invasive lung adenocarcinoma | ||
| MIA: Minimally invasive adenocarcinoma | ||
| Oral Cavity |  | EOLP: Erosive Oral lichen planus |
| LP: leukoplakia | ||
| NEOLP: Non-erosive oral lichen planus | ||
| OSCC: Oral squamous cell carcinoma | ||
| Prostate |  | BPH: Benign Prostatic Hyperplasia |
| Skin |  | AK: Actinic keratosis |
| cSCC: Cutaneous squamous cell carcinoma | ||
| SCCIS:squamous cell carcinoma in situ | ||
| Thyroid |  | 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 |
| Find out the enriched GO biological processes and KEGG pathways involved in transition from healthy to precancer to cancer |
| Figure of enriched GO biological processes. |
| Tissue | Disease Stage | Enriched GO biological Processes |
| Colorectum | AD |  |
| Colorectum | SER |  |
| Colorectum | MSS |  |
| Colorectum | MSI-H |  |
| Colorectum | FAP |  |
| ∗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). |
| Page: 1 2 3 4 5 6 7 8 9 |
| Enriched GO biological processes. |
| GO ID | Tissue | Disease Stage | Description | Gene Ratio | Bg Ratio | pvalue | p.adjust | Count |
| GO:00901308 | Lung | IAC | tissue migration | 66/2061 | 365/18723 | 3.32e-05 | 8.30e-04 | 66 |
| GO:00465784 | Lung | IAC | regulation of Ras protein signal transduction | 40/2061 | 189/18723 | 3.50e-05 | 8.65e-04 | 40 |
| GO:00106328 | Lung | IAC | regulation of epithelial cell migration | 55/2061 | 292/18723 | 4.68e-05 | 1.08e-03 | 55 |
| GO:00108118 | Lung | IAC | positive regulation of cell-substrate adhesion | 29/2061 | 123/18723 | 5.35e-05 | 1.21e-03 | 29 |
| GO:00016677 | Lung | IAC | ameboidal-type cell migration | 80/2061 | 475/18723 | 6.90e-05 | 1.47e-03 | 80 |
| GO:00435475 | Lung | IAC | positive regulation of GTPase activity | 48/2061 | 255/18723 | 1.40e-04 | 2.60e-03 | 48 |
| GO:00106347 | Lung | IAC | positive regulation of epithelial cell migration | 36/2061 | 176/18723 | 1.73e-04 | 3.07e-03 | 36 |
| GO:00019546 | Lung | IAC | positive regulation of cell-matrix adhesion | 16/2061 | 58/18723 | 3.85e-04 | 5.87e-03 | 16 |
| GO:00097438 | Lung | IAC | response to carbohydrate | 46/2061 | 253/18723 | 4.28e-04 | 6.37e-03 | 46 |
| GO:00518943 | Lung | IAC | positive regulation of focal adhesion assembly | 10/2061 | 28/18723 | 5.17e-04 | 7.37e-03 | 10 |
| GO:0032011 | Lung | IAC | ARF protein signal transduction | 8/2061 | 19/18723 | 5.25e-04 | 7.44e-03 | 8 |
| GO:0032012 | Lung | IAC | regulation of ARF protein signal transduction | 8/2061 | 19/18723 | 5.25e-04 | 7.44e-03 | 8 |
| GO:00109774 | Lung | IAC | negative regulation of neuron projection development | 27/2061 | 137/18723 | 1.88e-03 | 1.92e-02 | 27 |
| GO:01501173 | Lung | IAC | positive regulation of cell-substrate junction organization | 10/2061 | 33/18723 | 2.18e-03 | 2.15e-02 | 10 |
| GO:00342848 | Lung | IAC | response to monosaccharide | 39/2061 | 225/18723 | 2.75e-03 | 2.51e-02 | 39 |
| GO:00224118 | Lung | IAC | cellular component disassembly | 68/2061 | 443/18723 | 2.89e-03 | 2.60e-02 | 68 |
| GO:00310994 | Lung | IAC | regeneration | 34/2061 | 198/18723 | 5.73e-03 | 4.18e-02 | 34 |
| GO:0010812 | Lung | IAC | negative regulation of cell-substrate adhesion | 15/2061 | 68/18723 | 6.28e-03 | 4.49e-02 | 15 |
| GO:000716012 | Lung | AIS | cell-matrix adhesion | 60/1849 | 233/18723 | 2.19e-12 | 2.55e-09 | 60 |
| GO:003158913 | Lung | AIS | cell-substrate adhesion | 80/1849 | 363/18723 | 3.80e-12 | 3.16e-09 | 80 |
| Page: 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 |
| Enriched KEGG pathways. |
| Pathway ID | Tissue | Disease Stage | Description | Gene Ratio | Bg Ratio | pvalue | p.adjust | qvalue | Count |
| hsa040108 | Lung | IAC | MAPK signaling pathway | 62/1053 | 302/8465 | 3.54e-05 | 6.38e-04 | 4.24e-04 | 62 |
| hsa0401011 | Lung | IAC | MAPK signaling pathway | 62/1053 | 302/8465 | 3.54e-05 | 6.38e-04 | 4.24e-04 | 62 |
| hsa0401021 | Lung | AIS | MAPK signaling pathway | 57/961 | 302/8465 | 6.41e-05 | 9.43e-04 | 6.03e-04 | 57 |
| hsa0401031 | Lung | AIS | MAPK signaling pathway | 57/961 | 302/8465 | 6.41e-05 | 9.43e-04 | 6.03e-04 | 57 |
| hsa0401014 | Oral cavity | OSCC | MAPK signaling pathway | 165/3704 | 302/8465 | 7.11e-05 | 2.74e-04 | 1.40e-04 | 165 |
| hsa0401015 | Oral cavity | OSCC | MAPK signaling pathway | 165/3704 | 302/8465 | 7.11e-05 | 2.74e-04 | 1.40e-04 | 165 |
| hsa0401023 | Oral cavity | EOLP | MAPK signaling pathway | 68/1218 | 302/8465 | 7.48e-05 | 3.40e-04 | 2.01e-04 | 68 |
| hsa0401033 | Oral cavity | EOLP | MAPK signaling pathway | 68/1218 | 302/8465 | 7.48e-05 | 3.40e-04 | 2.01e-04 | 68 |
| hsa0401041 | Oral cavity | NEOLP | MAPK signaling pathway | 59/1112 | 302/8465 | 9.40e-04 | 4.67e-03 | 2.94e-03 | 59 |
| hsa0401051 | Oral cavity | NEOLP | MAPK signaling pathway | 59/1112 | 302/8465 | 9.40e-04 | 4.67e-03 | 2.94e-03 | 59 |
| hsa0401010 | Prostate | BPH | MAPK signaling pathway | 87/1718 | 302/8465 | 2.05e-04 | 1.13e-03 | 6.98e-04 | 87 |
| hsa0401013 | Prostate | BPH | MAPK signaling pathway | 87/1718 | 302/8465 | 2.05e-04 | 1.13e-03 | 6.98e-04 | 87 |
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Cell-cell communication analysis |
| Identification of potential cell-cell interactions between two cell types and their ligand-receptor pairs for different disease states |
| Ligand | Receptor | LRpair | Pathway | Tissue | Disease Stage |
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Single-cell gene regulatory network inference analysis |
| Find out the significant the regulons (TFs) and the target genes of each regulon across cell types for different disease states |
| TF | Cell Type | Tissue | Disease Stage | Target Gene | RSS | Regulon 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. |
| Page: 1 |
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Somatic mutation of malignant transformation related genes |
| Annotation of somatic variants for genes involved in malignant transformation |
| Hugo Symbol | Variant Class | Variant Classification | dbSNP RS | HGVSc | HGVSp | HGVSp Short | SWISSPROT | BIOTYPE | SIFT | PolyPhen | Tumor Sample Barcode | Tissue | Histology | Sex | Age | Stage | Therapy Types | Drugs | Outcome |
| MAP4K4 | SNV | Missense_Mutation | c.3526N>T | p.Val1176Phe | p.V1176F | protein_coding | deleterious_low_confidence(0.01) | probably_damaging(0.98) | TCGA-A8-A09X-01 | Breast | breast invasive carcinoma | Female | <65 | III/IV | Unknown | Unknown | SD | ||
| MAP4K4 | SNV | Missense_Mutation | c.3715N>C | p.Phe1239Leu | p.F1239L | protein_coding | deleterious_low_confidence(0) | probably_damaging(0.931) | TCGA-AC-A23H-01 | Breast | breast invasive carcinoma | Female | >=65 | I/II | Unknown | Unknown | PD | ||
| MAP4K4 | SNV | Missense_Mutation | c.451N>T | p.His151Tyr | p.H151Y | protein_coding | deleterious_low_confidence(0) | probably_damaging(0.957) | TCGA-AC-A2FG-01 | Breast | breast invasive carcinoma | Female | >=65 | I/II | Hormone Therapy | arimidex | CR | ||
| MAP4K4 | SNV | Missense_Mutation | novel | c.643N>A | p.Asp215Asn | p.D215N | protein_coding | deleterious_low_confidence(0) | probably_damaging(0.994) | TCGA-BH-A0B6-01 | Breast | breast invasive carcinoma | Female | <65 | I/II | Unknown | Unknown | SD | |
| MAP4K4 | SNV | Missense_Mutation | c.1246G>C | p.Glu416Gln | p.E416Q | protein_coding | tolerated_low_confidence(0.09) | possibly_damaging(0.888) | TCGA-D8-A27G-01 | Breast | breast invasive carcinoma | Female | >=65 | I/II | Unknown | Unknown | SD | ||
| MAP4K4 | SNV | Missense_Mutation | c.592N>A | p.Glu198Lys | p.E198K | protein_coding | deleterious_low_confidence(0) | probably_damaging(0.991) | TCGA-E2-A1LG-01 | Breast | breast invasive carcinoma | Female | <65 | I/II | Chemotherapy | doxorubicin | SD | ||
| MAP4K4 | SNV | Missense_Mutation | c.673N>C | p.Glu225Gln | p.E225Q | protein_coding | deleterious_low_confidence(0.02) | probably_damaging(0.991) | TCGA-E2-A1LG-01 | Breast | breast invasive carcinoma | Female | <65 | I/II | Chemotherapy | doxorubicin | SD | ||
| MAP4K4 | SNV | Missense_Mutation | c.2322N>C | p.Leu774Phe | p.L774F | protein_coding | tolerated_low_confidence(0.59) | probably_damaging(0.991) | TCGA-GM-A2DI-01 | Breast | breast invasive carcinoma | Female | <65 | I/II | Chemotherapy | taxotere | CR | ||
| MAP4K4 | SNV | Missense_Mutation | novel | c.2741N>C | p.Gly914Ala | p.G914A | protein_coding | tolerated_low_confidence(0.39) | probably_damaging(0.997) | TCGA-OL-A5RW-01 | Breast | breast invasive carcinoma | Female | <65 | I/II | Chemotherapy | adriamycin | CR | |
| MAP4K4 | insertion | Nonsense_Mutation | novel | c.1598_1599insGGAGGGTCAGACATAGACACAAGAGACGTAGAT | p.Asp533delinsGluGluGlyGlnThrTerThrGlnGluThrTerIle | p.D533delinsEEGQT*TQET*I | protein_coding | TCGA-AO-A0J9-01 | Breast | breast invasive carcinoma | Female | <65 | III/IV | Chemotherapy | cyclophosphamide | PD |
| Page: 1 2 3 4 5 6 7 8 9 10 11 12 |
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Related drugs of malignant transformation related genes |
| Identification of chemicals and drugs interact with genes involved in malignant transfromation |
| (DGIdb 4.0) |
| Entrez ID | Symbol | Category | Interaction Types | Drug Claim Name | Drug Name | PMIDs |
| 9448 | MAP4K4 | DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, ENZYME | CYC-116 | CYC-116 | ||
| 9448 | MAP4K4 | DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, ENZYME | SOTRASTAURIN | SOTRASTAURIN | ||
| 9448 | MAP4K4 | DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, ENZYME | PAZOPANIB | PAZOPANIB | ||
| 9448 | MAP4K4 | DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, ENZYME | DNDI1417467 | CHEMBL1997335 | ||
| 9448 | MAP4K4 | DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, ENZYME | AST-487 | AST-487 | ||
| 9448 | MAP4K4 | DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, ENZYME | PD-0166285 | PD-0166285 | ||
| 9448 | MAP4K4 | DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, ENZYME | SB-220025 | SB-220025 | ||
| 9448 | MAP4K4 | DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, ENZYME | CEDIRANIB | CEDIRANIB | ||
| 9448 | MAP4K4 | DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, ENZYME | OSI-632 | OSI-632 | ||
| 9448 | MAP4K4 | DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, ENZYME | AZD-1152-HQPA | AZD-1152-HQPA |
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