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: AMD1

Gene summary for AMD1

Gene summary.

Gene information	Species	Human
	Gene symbol	AMD1
	Gene ID	262
	Gene name	adenosylmethionine decarboxylase 1
	Gene Alias	ADOMETDC
	Cytomap	6q21
	Gene Type	protein-coding
	GO ID	GO:0006139
	UniProtAcc	A0A088AWN0

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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
262	AMD1	EEC-subject1	Human	Endometrium	EEC	1.72e-02	-1.36e-01	-0.2682
262	AMD1	EEC-subject2	Human	Endometrium	EEC	1.46e-03	-1.95e-01	-0.2607
262	AMD1	EEC-subject3	Human	Endometrium	EEC	1.13e-21	-2.35e-01	-0.2525
262	AMD1	GSM5276937	Human	Endometrium	EEC	1.29e-11	4.07e-01	-0.0897
262	AMD1	GSM6177620_NYU_UCEC1_lib1_lib1	Human	Endometrium	EEC	4.19e-19	-2.33e-01	-0.1869
262	AMD1	GSM6177620_NYU_UCEC1_lib2_lib2	Human	Endometrium	EEC	5.79e-18	-2.73e-01	-0.1875
262	AMD1	GSM6177620_NYU_UCEC1_lib3_lib3	Human	Endometrium	EEC	1.17e-21	-1.68e-01	-0.1883
262	AMD1	GSM6177621_NYU_UCEC2_lib1_lib1	Human	Endometrium	EEC	1.05e-18	-2.41e-01	-0.1934
262	AMD1	GSM6177622_NYU_UCEC3_lib1_lib1	Human	Endometrium	EEC	3.60e-31	-1.80e-01	-0.1917
262	AMD1	GSM6177622_NYU_UCEC3_lib2_lib2	Human	Endometrium	EEC	4.78e-31	-1.49e-01	-0.1916
262	AMD1	LZE24T	Human	Esophagus	ESCC	1.05e-08	9.64e-01	0.0596
262	AMD1	LZE6T	Human	Esophagus	ESCC	2.93e-02	2.69e-01	0.0845
262	AMD1	P1T-E	Human	Esophagus	ESCC	2.65e-03	4.11e-02	0.0875
262	AMD1	P2T-E	Human	Esophagus	ESCC	2.63e-07	1.65e-01	0.1177
262	AMD1	P4T-E	Human	Esophagus	ESCC	8.01e-10	6.44e-01	0.1323
262	AMD1	P5T-E	Human	Esophagus	ESCC	2.04e-09	3.48e-01	0.1327
262	AMD1	P8T-E	Human	Esophagus	ESCC	2.81e-12	6.44e-01	0.0889
262	AMD1	P10T-E	Human	Esophagus	ESCC	1.12e-10	2.31e-01	0.116
262	AMD1	P12T-E	Human	Esophagus	ESCC	1.30e-31	1.33e+00	0.1122
262	AMD1	P15T-E	Human	Esophagus	ESCC	2.96e-22	1.19e+00	0.1149

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
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
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).

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Enriched GO biological processes.

GO ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	Count
GO:0010876	Colorectum	AD	lipid localization	120/3918	448/18723	1.59e-03	1.33e-02	120
GO:0006869	Colorectum	AD	lipid transport	108/3918	398/18723	1.67e-03	1.39e-02	108
GO:0097305	Colorectum	AD	response to alcohol	71/3918	253/18723	4.01e-03	2.80e-02	71
GO:00973051	Colorectum	MSS	response to alcohol	66/3467	253/18723	1.73e-03	1.54e-02	66
GO:00108761	Colorectum	MSS	lipid localization	104/3467	448/18723	6.76e-03	4.38e-02	104
GO:00973052	Colorectum	MSI-H	response to alcohol	33/1319	253/18723	4.53e-04	9.61e-03	33
GO:00068691	Colorectum	FAP	lipid transport	81/2622	398/18723	2.84e-04	3.76e-03	81
GO:00973053	Colorectum	FAP	response to alcohol	55/2622	253/18723	5.05e-04	5.78e-03	55
GO:0097306	Colorectum	FAP	cellular response to alcohol	25/2622	93/18723	7.87e-04	8.29e-03	25
GO:00108762	Colorectum	FAP	lipid localization	85/2622	448/18723	1.92e-03	1.63e-02	85
GO:007252117	Endometrium	EEC	purine-containing compound metabolic process	73/2168	416/18723	1.82e-04	2.24e-03	73
GO:007252214	Endometrium	EEC	purine-containing compound biosynthetic process	37/2168	200/18723	2.62e-03	1.90e-02	37
GO:00065952	Endometrium	EEC	polyamine metabolic process	7/2168	18/18723	2.76e-03	1.97e-02	7
GO:00067906	Esophagus	ESCC	sulfur compound metabolic process	201/8552	339/18723	2.64e-07	3.94e-06	201
GO:0072521111	Esophagus	ESCC	purine-containing compound metabolic process	238/8552	416/18723	1.20e-06	1.49e-05	238
GO:00442725	Esophagus	ESCC	sulfur compound biosynthetic process	96/8552	148/18723	1.86e-06	2.16e-05	96
GO:007252217	Esophagus	ESCC	purine-containing compound biosynthetic process	120/8552	200/18723	3.02e-05	2.51e-04	120
GO:19016574	Esophagus	ESCC	glycosyl compound metabolic process	57/8552	88/18723	2.32e-04	1.44e-03	57
GO:0097305111	Esophagus	ESCC	response to alcohol	138/8552	253/18723	2.70e-03	1.14e-02	138
GO:00091163	Esophagus	ESCC	nucleoside metabolic process	39/8552	62/18723	4.68e-03	1.82e-02	39

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa002704	Endometrium	EEC	Cysteine and methionine metabolism	15/1237	52/8465	6.02e-03	3.12e-02	2.33e-02	15
hsa0027011	Endometrium	EEC	Cysteine and methionine metabolism	15/1237	52/8465	6.02e-03	3.12e-02	2.33e-02	15
hsa00270	Liver	Cirrhotic	Cysteine and methionine metabolism	27/2530	52/8465	6.98e-04	4.15e-03	2.56e-03	27
hsa003308	Liver	Cirrhotic	Arginine and proline metabolism	25/2530	50/8465	2.18e-03	9.41e-03	5.80e-03	25
hsa002701	Liver	Cirrhotic	Cysteine and methionine metabolism	27/2530	52/8465	6.98e-04	4.15e-03	2.56e-03	27
hsa0033011	Liver	Cirrhotic	Arginine and proline metabolism	25/2530	50/8465	2.18e-03	9.41e-03	5.80e-03	25
hsa002702	Liver	HCC	Cysteine and methionine metabolism	35/4020	52/8465	3.03e-03	9.94e-03	5.53e-03	35
hsa0033021	Liver	HCC	Arginine and proline metabolism	33/4020	50/8465	6.28e-03	1.77e-02	9.83e-03	33
hsa002703	Liver	HCC	Cysteine and methionine metabolism	35/4020	52/8465	3.03e-03	9.94e-03	5.53e-03	35
hsa0033031	Liver	HCC	Arginine and proline metabolism	33/4020	50/8465	6.28e-03	1.77e-02	9.83e-03	33
hsa0033010	Oral cavity	OSCC	Arginine and proline metabolism	30/3704	50/8465	1.50e-02	3.26e-02	1.66e-02	30
hsa0033013	Oral cavity	OSCC	Arginine and proline metabolism	30/3704	50/8465	1.50e-02	3.26e-02	1.66e-02	30
hsa0033023	Oral cavity	LP	Arginine and proline metabolism	26/2418	50/8465	3.94e-04	2.08e-03	1.34e-03	26
hsa0033033	Oral cavity	LP	Arginine and proline metabolism	26/2418	50/8465	3.94e-04	2.08e-03	1.34e-03	26
hsa003309	Prostate	BPH	Arginine and proline metabolism	18/1718	50/8465	7.17e-03	2.32e-02	1.43e-02	18
hsa0033012	Prostate	BPH	Arginine and proline metabolism	18/1718	50/8465	7.17e-03	2.32e-02	1.43e-02	18
hsa0033022	Prostate	Tumor	Arginine and proline metabolism	19/1791	50/8465	4.73e-03	1.67e-02	1.03e-02	19
hsa0033032	Prostate	Tumor	Arginine and proline metabolism	19/1791	50/8465	4.73e-03	1.67e-02	1.03e-02	19

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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

AMD1

SNV

Missense_Mutation

novel

c.722C>T

p.Thr241Ile

p.T241I

P17707

protein_coding

deleterious(0)

probably_damaging(0.995)

TCGA-AO-A0J9-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

AMD1

SNV

Missense_Mutation

c.793N>A

p.Asp265Asn

p.D265N

P17707

protein_coding

tolerated(0.31)

benign(0.098)

TCGA-C8-A12T-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

AMD1

SNV

Missense_Mutation

c.574N>C

p.Phe192Leu

p.F192L

P17707

protein_coding

deleterious(0.04)

possibly_damaging(0.791)

TCGA-D8-A1XK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine+cyclophosphamide

AMD1

insertion

In_Frame_Ins

novel

c.724_725insAAATATCAGATAAAATATTTTTAG

p.Ile242delinsLysIleSerAspLysIlePheLeuVal

p.I242delinsKISDKIFLV

P17707

protein_coding

TCGA-AO-A0J9-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

AMD1

SNV

Missense_Mutation

novel

c.699N>C

p.Met233Ile

p.M233I

P17707

protein_coding

tolerated(0.97)

benign(0.019)

TCGA-C5-A1MH-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

cisplatin

AMD1

SNV

Missense_Mutation

c.146G>C

p.Cys49Ser

p.C49S

P17707

protein_coding

deleterious(0.01)

probably_damaging(0.995)

TCGA-C5-A2LX-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

AMD1

SNV

Missense_Mutation

c.999G>C

p.Gln333His

p.Q333H

P17707

protein_coding

tolerated_low_confidence(0.09)

benign(0.007)

TCGA-JX-A3Q0-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unknown

AMD1

SNV

Missense_Mutation

novel

c.863N>G

p.Gln288Arg

p.Q288R

P17707

protein_coding

tolerated(0.08)

benign(0.068)

TCGA-A6-2672-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Unknown

AMD1

SNV

Missense_Mutation

novel

c.686N>T

p.Ser229Leu

p.S229L

P17707

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-A6-6141-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Chemotherapy

5-fu

AMD1

SNV

Missense_Mutation

c.502N>T

p.Arg168Trp

p.R168W

P17707

protein_coding

tolerated(0.2)

benign(0.015)

TCGA-AA-3510-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

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
262	AMD1	ENZYME, DRUGGABLE GENOME		ORG 34517/34850
262	AMD1	ENZYME, DRUGGABLE GENOME		Tromethamine	TROMETHAMINE

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