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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	Gene summary
	Malignant transformation analysis
	Malignant transformation related pathway analysis
	Cell-cell communication analysis
	Single-cell gene regulatory network inference analysis
	Somatic mutation of malignant transformation related genes
	Related drugs of malignant transformation related genes

Gene: AMT

Gene summary for AMT

Gene summary.

Gene information	Species	Human
	Gene symbol	AMT
	Gene ID	275
	Gene name	aminomethyltransferase
	Gene Alias	GCE
	Cytomap	3p21.31
	Gene Type	protein-coding
	GO ID	GO:0006082
	UniProtAcc	A0A024R2U7

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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
275	AMT	HCC1_Meng	Human	Liver	HCC	2.62e-95	1.65e-01	0.0246
275	AMT	HCC2_Meng	Human	Liver	HCC	3.00e-03	-2.33e-03	0.0107
275	AMT	cirrhotic1	Human	Liver	Cirrhotic	1.38e-02	8.85e-02	0.0202
275	AMT	cirrhotic2	Human	Liver	Cirrhotic	8.19e-04	1.33e-01	0.0201
275	AMT	HCC1	Human	Liver	HCC	5.22e-06	3.21e+00	0.5336
275	AMT	HCC2	Human	Liver	HCC	1.20e-02	1.68e+00	0.5341
275	AMT	S015	Human	Liver	HCC	6.02e-04	3.38e-01	0.2375
275	AMT	S016	Human	Liver	HCC	2.72e-03	2.44e-01	0.2243

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Liver		HCC: Hepatocellular carcinoma
Liver		NAFLD: Non-alcoholic fatty liver disease

∗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).

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Enriched GO biological processes.

GO ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	Count
GO:19001828	Endometrium	AEH	positive regulation of protein localization to nucleus	25/2100	87/18723	6.36e-06	1.55e-04	25
GO:00431229	Endometrium	AEH	regulation of I-kappaB kinase/NF-kappaB signaling	52/2100	249/18723	6.58e-06	1.59e-04	52
GO:00330022	Endometrium	AEH	muscle cell proliferation	51/2100	248/18723	1.26e-05	2.77e-04	51
GO:00431238	Endometrium	AEH	positive regulation of I-kappaB kinase/NF-kappaB signaling	41/2100	186/18723	1.59e-05	3.32e-04	41
GO:00345049	Endometrium	AEH	protein localization to nucleus	57/2100	290/18723	1.65e-05	3.42e-04	57
GO:00015589	Endometrium	AEH	regulation of cell growth	75/2100	414/18723	1.79e-05	3.65e-04	75
GO:00434105	Endometrium	AEH	positive regulation of MAPK cascade	84/2100	480/18723	2.19e-05	4.25e-04	84
GO:00018224	Endometrium	AEH	kidney development	57/2100	293/18723	2.25e-05	4.35e-04	57
GO:00072498	Endometrium	AEH	I-kappaB kinase/NF-kappaB signaling	55/2100	281/18723	2.60e-05	4.88e-04	55
GO:19001809	Endometrium	AEH	regulation of protein localization to nucleus	32/2100	136/18723	3.42e-05	6.06e-04	32
GO:005254816	Endometrium	AEH	regulation of endopeptidase activity	76/2100	432/18723	4.42e-05	7.43e-04	76
GO:004328116	Endometrium	AEH	regulation of cysteine-type endopeptidase activity involved in apoptotic process	43/2100	209/18723	5.77e-05	9.10e-04	43
GO:005110116	Endometrium	AEH	regulation of DNA binding	28/2100	118/18723	8.80e-05	1.29e-03	28
GO:00083616	Endometrium	AEH	regulation of cell size	38/2100	181/18723	9.69e-05	1.40e-03	38
GO:004586116	Endometrium	AEH	negative regulation of proteolysis	63/2100	351/18723	1.07e-04	1.53e-03	63
GO:200011616	Endometrium	AEH	regulation of cysteine-type endopeptidase activity	46/2100	235/18723	1.14e-04	1.62e-03	46
GO:00431128	Endometrium	AEH	receptor metabolic process	35/2100	166/18723	1.64e-04	2.15e-03	35
GO:00465452	Endometrium	AEH	development of primary female sexual characteristics	24/2100	100/18723	2.27e-04	2.75e-03	24
GO:00085852	Endometrium	AEH	female gonad development	23/2100	95/18723	2.65e-04	3.09e-03	23
GO:00457877	Endometrium	AEH	positive regulation of cell cycle	56/2100	313/18723	2.73e-04	3.14e-03	56

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0120021	Liver	Cirrhotic	Carbon metabolism	64/2530	115/8465	6.37e-09	1.18e-07	7.26e-08	64
hsa006304	Liver	Cirrhotic	Glyoxylate and dicarboxylate metabolism	20/2530	30/8465	3.36e-05	2.54e-04	1.57e-04	20
hsa00260	Liver	Cirrhotic	Glycine, serine and threonine metabolism	22/2530	40/8465	7.85e-04	4.51e-03	2.78e-03	22
hsa0120031	Liver	Cirrhotic	Carbon metabolism	64/2530	115/8465	6.37e-09	1.18e-07	7.26e-08	64
hsa0063011	Liver	Cirrhotic	Glyoxylate and dicarboxylate metabolism	20/2530	30/8465	3.36e-05	2.54e-04	1.57e-04	20
hsa002601	Liver	Cirrhotic	Glycine, serine and threonine metabolism	22/2530	40/8465	7.85e-04	4.51e-03	2.78e-03	22
hsa0120041	Liver	HCC	Carbon metabolism	89/4020	115/8465	3.92e-11	6.56e-10	3.65e-10	89
hsa0063021	Liver	HCC	Glyoxylate and dicarboxylate metabolism	24/4020	30/8465	2.66e-04	1.24e-03	6.88e-04	24
hsa006702	Liver	HCC	One carbon pool by folate	17/4020	20/8465	6.04e-04	2.50e-03	1.39e-03	17
hsa002602	Liver	HCC	Glycine, serine and threonine metabolism	28/4020	40/8465	3.28e-03	1.07e-02	5.93e-03	28
hsa0120051	Liver	HCC	Carbon metabolism	89/4020	115/8465	3.92e-11	6.56e-10	3.65e-10	89
hsa0063031	Liver	HCC	Glyoxylate and dicarboxylate metabolism	24/4020	30/8465	2.66e-04	1.24e-03	6.88e-04	24
hsa0067011	Liver	HCC	One carbon pool by folate	17/4020	20/8465	6.04e-04	2.50e-03	1.39e-03	17
hsa002603	Liver	HCC	Glycine, serine and threonine metabolism	28/4020	40/8465	3.28e-03	1.07e-02	5.93e-03	28

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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

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.

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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

AMT

insertion

In_Frame_Ins

novel

c.958_959insAGGTCCAGGGCTACA

p.Arg320delinsGlnValGlnGlyTyrSer

p.R320delinsQVQGYS

P48728

protein_coding

TCGA-A2-A0CP-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

AMT

insertion

Frame_Shift_Ins

novel

c.1047_1048insAAGGAAGTAAATTTAAGATGGATATTTAA

p.Gly350LysfsTer17

p.G350Kfs*17

P48728

protein_coding

TCGA-A8-A07G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

5-fluorouracil

AMT

insertion

In_Frame_Ins

novel

c.1053_1054insACTTCCGTGTTTAAT

p.Cys351_Pro352insThrSerValPheAsn

p.C351_P352insTSVFN

P48728

protein_coding

TCGA-AR-A0TY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

AMT

SNV

Missense_Mutation

c.468N>T

p.Met156Ile

p.M156I

P48728

protein_coding

tolerated(0.76)

benign(0.103)

TCGA-AA-3492-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

AMT

SNV

Missense_Mutation

rs749087037

c.59N>T

p.Pro20Leu

p.P20L

P48728

protein_coding

tolerated(0.4)

benign(0)

TCGA-AZ-6598-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

AMT

SNV

Missense_Mutation

c.791T>A

p.Leu264Gln

p.L264Q

P48728

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-CM-6166-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

AMT

SNV

Missense_Mutation

rs372496075

c.583N>A

p.Val195Met

p.V195M

P48728

protein_coding

tolerated(0.06)

possibly_damaging(0.503)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

AMT

SNV

Missense_Mutation

novel

c.901N>A

p.Asp301Asn

p.D301N

P48728

protein_coding

tolerated(0.32)

benign(0.129)

TCGA-AJ-A3EL-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

AMT

SNV

Missense_Mutation

c.587C>T

p.Ala196Val

p.A196V

P48728

protein_coding

tolerated(0.2)

benign(0.041)

TCGA-B5-A11E-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

AMT

SNV

Missense_Mutation

novel

c.505N>T

p.Asp169Tyr

p.D169Y

P48728

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-EO-A3B0-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

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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

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