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: PDGFRA

Gene summary for PDGFRA

Gene summary.

Gene information	Species	Human
	Gene symbol	PDGFRA
	Gene ID	5156
	Gene name	platelet derived growth factor receptor alpha
	Gene Alias	CD140A
	Cytomap	4q12
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	P16234

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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
5156	PDGFRA	male-WTA	Human	Thyroid	PTC	2.99e-03	4.90e-02	0.1037
5156	PDGFRA	ATC12	Human	Thyroid	ATC	1.59e-67	1.44e+00	0.34
5156	PDGFRA	ATC13	Human	Thyroid	ATC	1.03e-63	1.45e+00	0.34
5156	PDGFRA	ATC3	Human	Thyroid	ATC	6.43e-04	3.19e-01	0.338
5156	PDGFRA	ATC4	Human	Thyroid	ATC	1.30e-83	1.61e+00	0.34
5156	PDGFRA	ATC5	Human	Thyroid	ATC	2.03e-80	1.53e+00	0.34

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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:0070527111	Thyroid	PTC	platelet aggregation	33/5968	67/18723	2.24e-03	1.18e-02	33
GO:00101713	Thyroid	PTC	body morphogenesis	23/5968	43/18723	2.66e-03	1.35e-02	23
GO:004886318	Thyroid	PTC	stem cell differentiation	85/5968	206/18723	2.71e-03	1.36e-02	85
GO:00720067	Thyroid	PTC	nephron development	61/5968	142/18723	3.49e-03	1.69e-02	61
GO:00603234	Thyroid	PTC	head morphogenesis	18/5968	32/18723	3.72e-03	1.79e-02	18
GO:004654612	Thyroid	PTC	development of primary male sexual characteristics	60/5968	142/18723	5.79e-03	2.61e-02	60
GO:00333271	Thyroid	PTC	Leydig cell differentiation	8/5968	11/18723	6.50e-03	2.83e-02	8
GO:004814612	Thyroid	PTC	positive regulation of fibroblast proliferation	24/5968	48/18723	6.73e-03	2.90e-02	24
GO:000858412	Thyroid	PTC	male gonad development	59/5968	141/18723	7.88e-03	3.33e-02	59
GO:00328356	Thyroid	PTC	glomerulus development	29/5968	62/18723	9.96e-03	4.07e-02	29
GO:00182126	Thyroid	PTC	peptidyl-tyrosine modification	142/5968	378/18723	1.02e-02	4.14e-02	142
GO:001470617	Thyroid	PTC	striated muscle tissue development	144/5968	384/18723	1.05e-02	4.22e-02	144
GO:000697934	Thyroid	ATC	response to oxidative stress	246/6293	446/18723	2.98e-21	6.09e-19	246
GO:006219734	Thyroid	ATC	cellular response to chemical stress	188/6293	337/18723	3.16e-17	3.07e-15	188
GO:0032970210	Thyroid	ATC	regulation of actin filament-based process	208/6293	397/18723	5.82e-15	3.80e-13	208
GO:0032956210	Thyroid	ATC	regulation of actin cytoskeleton organization	190/6293	358/18723	1.73e-14	1.01e-12	190
GO:003459934	Thyroid	ATC	cellular response to oxidative stress	158/6293	288/18723	7.35e-14	3.94e-12	158
GO:000030234	Thyroid	ATC	response to reactive oxygen species	128/6293	222/18723	1.38e-13	7.00e-12	128
GO:004206034	Thyroid	ATC	wound healing	210/6293	422/18723	3.33e-12	1.37e-10	210
GO:000170126	Thyroid	ATC	in utero embryonic development	183/6293	367/18723	6.62e-11	2.11e-09	183

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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
PDGFA	PDGFRA	PDGFA_PDGFRA	PDGF	Breast	ADJ
PDGFB	PDGFRA	PDGFB_PDGFRA	PDGF	Breast	ADJ
PDGFA	PDGFRA	PDGFA_PDGFRA	PDGF	Breast	DCIS
PDGFB	PDGFRA	PDGFB_PDGFRA	PDGF	Breast	DCIS
PDGFA	PDGFRA	PDGFA_PDGFRA	PDGF	Breast	Healthy
PDGFA	PDGFRA	PDGFA_PDGFRA	PDGF	Breast	IDC
PDGFC	PDGFRA	PDGFC_PDGFRA	PDGF	Breast	IDC
PDGFA	PDGFRA	PDGFA_PDGFRA	PDGF	Cervix	ADJ
PDGFA	PDGFRA	PDGFA_PDGFRA	PDGF	Cervix	CC
PDGFC	PDGFRA	PDGFC_PDGFRA	PDGF	Cervix	CC
PDGFA	PDGFRA	PDGFA_PDGFRA	PDGF	Cervix	Precancer
PDGFC	PDGFRA	PDGFC_PDGFRA	PDGF	Cervix	Precancer
PDGFB	PDGFRA	PDGFB_PDGFRA	PDGF	CRC	AD
PDGFC	PDGFRA	PDGFC_PDGFRA	PDGF	CRC	AD
PDGFC	PDGFRA	PDGFC_PDGFRA	PDGF	CRC	ADJ
PDGFA	PDGFRA	PDGFA_PDGFRA	PDGF	CRC	CRC
PDGFC	PDGFRA	PDGFC_PDGFRA	PDGF	CRC	CRC
PDGFA	PDGFRA	PDGFA_PDGFRA	PDGF	CRC	MSS
PDGFB	PDGFRA	PDGFB_PDGFRA	PDGF	CRC	MSS
PDGFA	PDGFRA	PDGFA_PDGFRA	PDGF	Endometrium	ADJ

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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

PDGFRA

SNV

Missense_Mutation

c.2942G>C

p.Arg981Pro

p.R981P

P16234

protein_coding

deleterious(0.03)

possibly_damaging(0.862)

TCGA-A2-A0T0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

PDGFRA

SNV

Missense_Mutation

c.2953N>A

p.Asp985Asn

p.D985N

P16234

protein_coding

tolerated(0.27)

benign(0.318)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PDGFRA

SNV

Missense_Mutation

c.1711N>A

p.Glu571Lys

p.E571K

P16234

protein_coding

deleterious(0)

probably_damaging(0.989)

TCGA-AO-A12D-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

PDGFRA

SNV

Missense_Mutation

rs763325080

c.2465N>A

p.Arg822His

p.R822H

P16234

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-AR-A1AV-01

Breast

breast invasive carcinoma

Male

>=65

I/II

Chemotherapy

cytoxan

PDGFRA

SNV

Missense_Mutation

rs767697835

c.3223N>A

p.Asp1075Asn

p.D1075N

P16234

protein_coding

deleterious_low_confidence(0.01)

possibly_damaging(0.631)

TCGA-D8-A1XQ-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PDGFRA

SNV

Missense_Mutation

c.1666G>A

p.Glu556Lys

p.E556K

P16234

protein_coding

deleterious(0)

probably_damaging(0.993)

TCGA-D8-A27G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PDGFRA

insertion

Frame_Shift_Ins

novel

c.905_906insATCTCCATCTCTTAGAATCTTTCTCCACCATCTCTCCTTTCTAG

p.Met302IlefsTer51

p.M302Ifs*51

P16234

protein_coding

TCGA-A2-A0CX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

PDGFRA

insertion

Nonsense_Mutation

novel

c.2875_2876insCCATGTTCAGCTAATTTTTGTATTTTT

p.Lys959delinsThrMetPheSerTerPheLeuTyrPheTer

p.K959delinsTMFS*FLYF*

P16234

protein_coding

TCGA-A7-A0CJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

PDGFRA

insertion

Frame_Shift_Ins

novel

c.2035_2036insTG

p.Tyr679LeufsTer17

p.Y679Lfs*17

P16234

protein_coding

TCGA-A8-A06O-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

letrozole

PDGFRA

insertion

Nonsense_Mutation

novel

c.2036_2037insGAACAGGAAGT

p.Tyr679Ter

p.Y679*

P16234

protein_coding

TCGA-A8-A06O-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

letrozole

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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
5156	PDGFRA	TYROSINE KINASE, KINASE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME, EXTERNAL SIDE OF PLASMA MEMBRANE, DRUG RESISTANCE		IMATINIB	IMATINIB	15928335,15685537,22718859,16638875,15146165,12949711,26130666,25157968,24132921,14645423,16954519,18794084,22745105
5156	PDGFRA	TYROSINE KINASE, KINASE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME, EXTERNAL SIDE OF PLASMA MEMBRANE, DRUG RESISTANCE		DASATINIB	DASATINIB	15928335,15685537,22718859,16638875,15146165,12949711,26130666,25157968,14645423,16954519,18794084,22745105
5156	PDGFRA	TYROSINE KINASE, KINASE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME, EXTERNAL SIDE OF PLASMA MEMBRANE, DRUG RESISTANCE		VANDETANIB	VANDETANIB
5156	PDGFRA	TYROSINE KINASE, KINASE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME, EXTERNAL SIDE OF PLASMA MEMBRANE, DRUG RESISTANCE	inhibitor	363894199
5156	PDGFRA	TYROSINE KINASE, KINASE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME, EXTERNAL SIDE OF PLASMA MEMBRANE, DRUG RESISTANCE		CP-868596	CRENOLANIB
5156	PDGFRA	TYROSINE KINASE, KINASE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME, EXTERNAL SIDE OF PLASMA MEMBRANE, DRUG RESISTANCE	inhibitor	249565576	ENMD-2076
5156	PDGFRA	TYROSINE KINASE, KINASE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME, EXTERNAL SIDE OF PLASMA MEMBRANE, DRUG RESISTANCE		LINIFANIB	LINIFANIB
5156	PDGFRA	TYROSINE KINASE, KINASE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME, EXTERNAL SIDE OF PLASMA MEMBRANE, DRUG RESISTANCE	antibody	OLARATUMAB	OLARATUMAB
5156	PDGFRA	TYROSINE KINASE, KINASE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME, EXTERNAL SIDE OF PLASMA MEMBRANE, DRUG RESISTANCE	inhibitor	178102559	NINTEDANIB
5156	PDGFRA	TYROSINE KINASE, KINASE, CLINICALLY ACTIONABLE, DRUGGABLE GENOME, EXTERNAL SIDE OF PLASMA MEMBRANE, DRUG RESISTANCE		CYC-116	CYC-116

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