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: AFMID

Gene summary for AFMID

Gene summary.

Gene information	Species	Human
	Gene symbol	AFMID
	Gene ID	125061
	Gene name	arylformamidase
	Gene Alias	FKF
	Cytomap	17q25.3
	Gene Type	protein-coding
	GO ID	GO:0006082
	UniProtAcc	Q63HM1

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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
125061	AFMID	HTA11_1391_2000001011	Human	Colorectum	AD	8.56e-05	4.27e-01	-0.059
125061	AFMID	HTA11_866_3004761011	Human	Colorectum	AD	3.85e-06	3.01e-01	0.096
125061	AFMID	HTA11_10711_2000001011	Human	Colorectum	AD	1.59e-02	2.51e-01	0.0338
125061	AFMID	HTA11_99999965062_69753	Human	Colorectum	MSI-H	8.08e-09	1.54e+00	0.3487
125061	AFMID	HTA11_99999965104_69814	Human	Colorectum	MSS	4.61e-02	2.57e-01	0.281
125061	AFMID	HTA11_99999971662_82457	Human	Colorectum	MSS	1.11e-06	5.31e-01	0.3859
125061	AFMID	HTA11_99999974143_84620	Human	Colorectum	MSS	2.30e-11	5.39e-01	0.3005
125061	AFMID	A015-C-203	Human	Colorectum	FAP	1.58e-03	-4.21e-02	-0.1294
125061	AFMID	A001-C-108	Human	Colorectum	FAP	3.58e-02	-4.72e-02	-0.0272
125061	AFMID	A015-C-104	Human	Colorectum	FAP	5.15e-05	1.05e-03	-0.1899
125061	AFMID	A002-C-016	Human	Colorectum	FAP	2.53e-03	-1.46e-01	0.0521
125061	AFMID	A002-C-116	Human	Colorectum	FAP	1.54e-04	-8.73e-02	-0.0452
125061	AFMID	F034	Human	Colorectum	FAP	1.77e-02	-6.54e-02	-0.0665
125061	AFMID	AEH-subject1	Human	Endometrium	AEH	8.09e-26	7.18e-01	-0.3059
125061	AFMID	AEH-subject2	Human	Endometrium	AEH	3.13e-20	6.65e-01	-0.2525
125061	AFMID	AEH-subject3	Human	Endometrium	AEH	4.51e-14	5.69e-01	-0.2576
125061	AFMID	EEC-subject2	Human	Endometrium	EEC	7.40e-19	6.68e-01	-0.2607
125061	AFMID	GSM6177620_NYU_UCEC1_lib1_lib1	Human	Endometrium	EEC	8.89e-03	-6.47e-02	-0.1869
125061	AFMID	GSM6177620_NYU_UCEC1_lib3_lib3	Human	Endometrium	EEC	1.48e-05	-1.11e-01	-0.1883
125061	AFMID	GSM6177622_NYU_UCEC3_lib1_lib1	Human	Endometrium	EEC	2.26e-04	-4.89e-02	-0.1917

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Colorectum (GSE201348)		FAP: Familial adenomatous polyposis
		CRC: Colorectal cancer
Colorectum (HTA11)		AD: Adenomas
		SER: Sessile serrated lesions
		MSI-H: Microsatellite-high colorectal cancer
		MSS: Microsatellite stable colorectal cancer
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
GC		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
Liver		HCC: Hepatocellular carcinoma
		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:0009117	Colorectum	AD	nucleotide metabolic process	168/3918	489/18723	2.20e-12	3.36e-10	168
GO:0006753	Colorectum	AD	nucleoside phosphate metabolic process	169/3918	497/18723	4.99e-12	6.98e-10	169
GO:0044270	Colorectum	AD	cellular nitrogen compound catabolic process	147/3918	451/18723	3.35e-09	2.23e-07	147
GO:0046700	Colorectum	AD	heterocycle catabolic process	145/3918	445/18723	4.37e-09	2.84e-07	145
GO:0019439	Colorectum	AD	aromatic compound catabolic process	146/3918	467/18723	7.48e-08	3.84e-06	146
GO:1901361	Colorectum	AD	organic cyclic compound catabolic process	153/3918	495/18723	8.23e-08	4.18e-06	153
GO:0044282	Colorectum	AD	small molecule catabolic process	118/3918	376/18723	1.05e-06	3.55e-05	118
GO:1901293	Colorectum	AD	nucleoside phosphate biosynthetic process	80/3918	256/18723	6.31e-05	1.05e-03	80
GO:0009165	Colorectum	AD	nucleotide biosynthetic process	79/3918	254/18723	8.33e-05	1.30e-03	79
GO:0016054	Colorectum	AD	organic acid catabolic process	73/3918	240/18723	3.20e-04	3.81e-03	73
GO:0046395	Colorectum	AD	carboxylic acid catabolic process	70/3918	236/18723	9.06e-04	8.71e-03	70
GO:0006520	Colorectum	AD	cellular amino acid metabolic process	81/3918	284/18723	1.37e-03	1.19e-02	81
GO:00442702	Colorectum	MSS	cellular nitrogen compound catabolic process	141/3467	451/18723	2.95e-11	3.83e-09	141
GO:00467002	Colorectum	MSS	heterocycle catabolic process	139/3467	445/18723	4.37e-11	5.05e-09	139
GO:19013612	Colorectum	MSS	organic cyclic compound catabolic process	148/3467	495/18723	3.47e-10	3.18e-08	148
GO:00194392	Colorectum	MSS	aromatic compound catabolic process	140/3467	467/18723	8.56e-10	6.85e-08	140
GO:00091172	Colorectum	MSS	nucleotide metabolic process	144/3467	489/18723	1.87e-09	1.35e-07	144
GO:00067532	Colorectum	MSS	nucleoside phosphate metabolic process	145/3467	497/18723	3.25e-09	2.23e-07	145
GO:19012932	Colorectum	MSS	nucleoside phosphate biosynthetic process	71/3467	256/18723	1.80e-04	2.56e-03	71
GO:00091652	Colorectum	MSS	nucleotide biosynthetic process	70/3467	254/18723	2.44e-04	3.34e-03	70

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa00380	Colorectum	FAP	Tryptophan metabolism	13/1404	42/8465	1.54e-02	4.99e-02	3.03e-02	13
hsa003801	Colorectum	FAP	Tryptophan metabolism	13/1404	42/8465	1.54e-02	4.99e-02	3.03e-02	13
hsa012405	Esophagus	ESCC	Biosynthesis of cofactors	97/4205	153/8465	3.88e-04	1.35e-03	6.94e-04	97
hsa006306	Esophagus	ESCC	Glyoxylate and dicarboxylate metabolism	21/4205	30/8465	1.95e-02	4.35e-02	2.23e-02	21
hsa0124012	Esophagus	ESCC	Biosynthesis of cofactors	97/4205	153/8465	3.88e-04	1.35e-03	6.94e-04	97
hsa0063013	Esophagus	ESCC	Glyoxylate and dicarboxylate metabolism	21/4205	30/8465	1.95e-02	4.35e-02	2.23e-02	21
hsa006304	Liver	Cirrhotic	Glyoxylate and dicarboxylate metabolism	20/2530	30/8465	3.36e-05	2.54e-04	1.57e-04	20
hsa01240	Liver	Cirrhotic	Biosynthesis of cofactors	66/2530	153/8465	3.11e-04	1.99e-03	1.23e-03	66
hsa003802	Liver	Cirrhotic	Tryptophan metabolism	22/2530	42/8465	1.85e-03	8.37e-03	5.16e-03	22
hsa0063011	Liver	Cirrhotic	Glyoxylate and dicarboxylate metabolism	20/2530	30/8465	3.36e-05	2.54e-04	1.57e-04	20
hsa012401	Liver	Cirrhotic	Biosynthesis of cofactors	66/2530	153/8465	3.11e-04	1.99e-03	1.23e-03	66
hsa0038011	Liver	Cirrhotic	Tryptophan metabolism	22/2530	42/8465	1.85e-03	8.37e-03	5.16e-03	22
hsa012402	Liver	HCC	Biosynthesis of cofactors	103/4020	153/8465	4.67e-07	5.05e-06	2.81e-06	103
hsa0063021	Liver	HCC	Glyoxylate and dicarboxylate metabolism	24/4020	30/8465	2.66e-04	1.24e-03	6.88e-04	24
hsa012403	Liver	HCC	Biosynthesis of cofactors	103/4020	153/8465	4.67e-07	5.05e-06	2.81e-06	103
hsa0063031	Liver	HCC	Glyoxylate and dicarboxylate metabolism	24/4020	30/8465	2.66e-04	1.24e-03	6.88e-04	24

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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

AFMID

SNV

Missense_Mutation

rs374429075

c.748N>A

p.Glu250Lys

p.E250K

Q63HM1

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-D8-A1JJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine

AFMID

insertion

Frame_Shift_Ins

novel

c.358_359insGCTCACA

p.Ala120GlyfsTer81

p.A120Gfs*81

Q63HM1

protein_coding

TCGA-A8-A093-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

AFMID

insertion

In_Frame_Ins

novel

c.360_361insTATAATCCCACACATTGGGAGGCTGAGGCAGGA

p.Ala120_Val121insTyrAsnProThrHisTrpGluAlaGluAlaGly

p.A120_V121insYNPTHWEAEAG

Q63HM1

protein_coding

TCGA-A8-A093-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

AFMID

SNV

Missense_Mutation

rs143224831

c.304N>A

p.Gly102Arg

p.G102R

Q63HM1

protein_coding

deleterious(0.04)

probably_damaging(0.989)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

AFMID

SNV

Missense_Mutation

rs575961186

c.916N>G

p.Ile306Val

p.I306V

Q63HM1

protein_coding

tolerated(0.1)

benign(0.03)

TCGA-EA-A411-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

AFMID

SNV

Missense_Mutation

c.743N>T

p.Ser248Phe

p.S248F

Q63HM1

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-VS-A9UU-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

AFMID

SNV

Missense_Mutation

novel

c.745N>A

p.Pro249Thr

p.P249T

Q63HM1

protein_coding

tolerated(0.05)

probably_damaging(0.952)

TCGA-A6-5666-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

AFMID

SNV

Missense_Mutation

c.371N>C

p.Val124Ala

p.V124A

Q63HM1

protein_coding

deleterious(0.03)

benign(0.164)

TCGA-AA-3672-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Unknown

AFMID

SNV

Missense_Mutation

c.72N>T

p.Glu24Asp

p.E24D

Q63HM1

protein_coding

tolerated(0.09)

benign(0.015)

TCGA-CA-6717-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Chemotherapy

oxaliplatin

AFMID

SNV

Missense_Mutation

novel

c.650N>C

p.Asp217Ala

p.D217A

Q63HM1

protein_coding

tolerated(1)

benign(0.272)

TCGA-CK-6746-01

Colorectum

colon adenocarcinoma

Female

>=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

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