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: AMPD1

Gene summary for AMPD1

Gene summary.

Gene information	Species	Human
	Gene symbol	AMPD1
	Gene ID	270
	Gene name	adenosine monophosphate deaminase 1
	Gene Alias	MAD
	Cytomap	1p13.2
	Gene Type	protein-coding
	GO ID	GO:0006139
	UniProtAcc	P23109

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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
270	AMPD1	GSM5353218_PA_PB1B_Pool_1_2_S74_L003	Human	Prostate	Tumor	9.05e-11	9.42e-01	0.1479
270	AMPD1	GSM5353220_PA_PB1B_Pool_3_S51_L002	Human	Prostate	Tumor	1.91e-08	9.85e-01	0.1531

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Prostate		BPH: Benign Prostatic Hyperplasia

∗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:000915019	Prostate	Tumor	purine ribonucleotide metabolic process	109/3246	368/18723	3.30e-09	1.36e-07	109
GO:000925918	Prostate	Tumor	ribonucleotide metabolic process	110/3246	385/18723	2.45e-08	8.29e-07	110
GO:000616319	Prostate	Tumor	purine nucleotide metabolic process	111/3246	396/18723	6.46e-08	1.88e-06	111
GO:001969318	Prostate	Tumor	ribose phosphate metabolic process	111/3246	396/18723	6.46e-08	1.88e-06	111
GO:007252119	Prostate	Tumor	purine-containing compound metabolic process	115/3246	416/18723	8.47e-08	2.31e-06	115
GO:000915218	Prostate	Tumor	purine ribonucleotide biosynthetic process	53/3246	169/18723	5.62e-06	8.63e-05	53
GO:000926016	Prostate	Tumor	ribonucleotide biosynthetic process	54/3246	182/18723	2.71e-05	3.29e-04	54
GO:000911718	Prostate	Tumor	nucleotide metabolic process	120/3246	489/18723	2.81e-05	3.41e-04	120
GO:000675317	Prostate	Tumor	nucleoside phosphate metabolic process	121/3246	497/18723	3.81e-05	4.41e-04	121
GO:004639016	Prostate	Tumor	ribose phosphate biosynthetic process	55/3246	190/18723	4.89e-05	5.42e-04	55
GO:007252215	Prostate	Tumor	purine-containing compound biosynthetic process	55/3246	200/18723	2.16e-04	1.86e-03	55
GO:000616415	Prostate	Tumor	purine nucleotide biosynthetic process	53/3246	191/18723	2.18e-04	1.87e-03	53
GO:000916514	Prostate	Tumor	nucleotide biosynthetic process	61/3246	254/18723	4.03e-03	2.04e-02	61
GO:190129314	Prostate	Tumor	nucleoside phosphate biosynthetic process	61/3246	256/18723	4.84e-03	2.37e-02	61
GO:000912612	Prostate	Tumor	purine nucleoside monophosphate metabolic process	15/3246	44/18723	5.49e-03	2.61e-02	15
GO:00091676	Prostate	Tumor	purine ribonucleoside monophosphate metabolic process	14/3246	41/18723	7.07e-03	3.18e-02	14

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Enriched KEGG pathways.

Pathway ID

Tissue

Disease Stage

Description

Gene Ratio

Bg Ratio

pvalue

p.adjust

qvalue

Count

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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

AMPD1

SNV

Missense_Mutation

novel

c.1001N>G

p.Asp334Gly

p.D334G

P23109

protein_coding

deleterious(0)

probably_damaging(0.967)

TCGA-A2-A3XS-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cytoxan

AMPD1

SNV

Missense_Mutation

c.679C>G

p.Pro227Ala

p.P227A

P23109

protein_coding

deleterious(0.02)

probably_damaging(0.996)

TCGA-A8-A097-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

AMPD1

SNV

Missense_Mutation

c.1710G>T

p.Lys570Asn

p.K570N

P23109

protein_coding

tolerated(0.23)

benign(0.021)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

AMPD1

SNV

Missense_Mutation

c.2019N>T

p.Lys673Asn

p.K673N

P23109

protein_coding

deleterious(0)

probably_damaging(0.993)

TCGA-AO-A0J4-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

AMPD1

SNV

Missense_Mutation

novel

c.587C>T

p.Ser196Phe

p.S196F

P23109

protein_coding

deleterious(0)

probably_damaging(0.95)

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

AMPD1

SNV

Missense_Mutation

c.558N>C

p.Lys186Asn

p.K186N

P23109

protein_coding

tolerated(0.2)

benign(0.14)

TCGA-E2-A14Z-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

AMPD1

SNV

Missense_Mutation

c.1879C>G

p.His627Asp

p.H627D

P23109

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-EW-A1PH-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

AMPD1

insertion

Frame_Shift_Ins

novel

c.1287_1288insCAAGCATGTAAGCATGACCCTTCAGGCCTTCATAC

p.Tyr430GlnfsTer26

p.Y430Qfs*26

P23109

protein_coding

TCGA-AO-A0J9-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

AMPD1

SNV

Missense_Mutation

novel

c.1502N>T

p.Ser501Phe

p.S501F

P23109

protein_coding

deleterious(0)

possibly_damaging(0.595)

TCGA-C5-A1BL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

AMPD1

SNV

Missense_Mutation

novel

c.256N>A

p.Glu86Lys

p.E86K

P23109

protein_coding

deleterious(0)

possibly_damaging(0.847)

TCGA-C5-A905-01

Cervix

cervical & endocervical cancer

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
270	AMPD1	DRUGGABLE GENOME, ENZYME		methotrexate	METHOTREXATE	20386493,27217051,29520081,16947783,27992285
270	AMPD1	DRUGGABLE GENOME, ENZYME		regadenoson	REGADENOSON	26554440

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