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: PHGDH

Gene summary for PHGDH

Gene summary.

Gene information	Species	Human
	Gene symbol	PHGDH
	Gene ID	26227
	Gene name	phosphoglycerate dehydrogenase
	Gene Alias	3-PGDH
	Cytomap	1p12
	Gene Type	protein-coding
	GO ID	GO:0006082
	UniProtAcc	O43175

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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
26227	PHGDH	GSM4909282	Human	Breast	IDC	3.63e-29	7.08e-01	-0.0288
26227	PHGDH	GSM4909285	Human	Breast	IDC	5.60e-59	9.13e-01	0.21
26227	PHGDH	GSM4909287	Human	Breast	IDC	2.74e-05	3.58e-01	0.2057
26227	PHGDH	GSM4909293	Human	Breast	IDC	1.44e-06	-2.18e-01	0.1581
26227	PHGDH	GSM4909297	Human	Breast	IDC	2.37e-06	-2.15e-01	0.1517
26227	PHGDH	GSM4909301	Human	Breast	IDC	9.06e-08	-2.20e-01	0.1577
26227	PHGDH	GSM4909302	Human	Breast	IDC	1.51e-08	-2.48e-01	0.1545
26227	PHGDH	GSM4909311	Human	Breast	IDC	1.09e-06	-1.26e-01	0.1534
26227	PHGDH	GSM4909312	Human	Breast	IDC	9.13e-03	-1.53e-01	0.1552
26227	PHGDH	GSM4909316	Human	Breast	IDC	1.10e-02	4.01e-01	0.21
26227	PHGDH	GSM4909319	Human	Breast	IDC	3.30e-12	-2.38e-01	0.1563
26227	PHGDH	GSM4909321	Human	Breast	IDC	3.79e-06	-1.68e-01	0.1559
26227	PHGDH	M2	Human	Breast	IDC	5.22e-03	4.14e-01	0.21
26227	PHGDH	NCCBC5	Human	Breast	DCIS	3.27e-04	-9.15e-02	0.2046
26227	PHGDH	P1	Human	Breast	IDC	5.70e-03	-1.17e-01	0.1527
26227	PHGDH	P2	Human	Breast	IDC	4.44e-04	3.81e-01	0.21
26227	PHGDH	DCIS2	Human	Breast	DCIS	1.23e-34	1.30e-01	0.0085
26227	PHGDH	LZE7T	Human	Esophagus	ESCC	4.41e-04	5.14e-01	0.0667
26227	PHGDH	LZE24T	Human	Esophagus	ESCC	1.50e-11	7.41e-01	0.0596
26227	PHGDH	LZE21T	Human	Esophagus	ESCC	2.54e-03	4.34e-01	0.0655

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
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
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:000609113	Breast	IDC	generation of precursor metabolites and energy	103/1434	490/18723	1.53e-21	1.74e-18	103
GO:002290013	Breast	IDC	electron transport chain	51/1434	175/18723	2.23e-17	8.43e-15	51
GO:004206311	Breast	IDC	gliogenesis	39/1434	301/18723	8.63e-04	1.00e-02	39
GO:00100011	Breast	IDC	glial cell differentiation	31/1434	225/18723	1.04e-03	1.15e-02	31
GO:001605313	Breast	IDC	organic acid biosynthetic process	39/1434	316/18723	2.13e-03	1.99e-02	39
GO:004639413	Breast	IDC	carboxylic acid biosynthetic process	38/1434	314/18723	3.39e-03	2.83e-02	38
GO:000609123	Breast	DCIS	generation of precursor metabolites and energy	103/1390	490/18723	1.46e-22	1.65e-19	103
GO:002290023	Breast	DCIS	electron transport chain	51/1390	175/18723	6.01e-18	2.62e-15	51
GO:00420632	Breast	DCIS	gliogenesis	39/1390	301/18723	4.76e-04	6.25e-03	39
GO:00100012	Breast	DCIS	glial cell differentiation	31/1390	225/18723	6.24e-04	7.87e-03	31
GO:001605322	Breast	DCIS	organic acid biosynthetic process	38/1390	316/18723	2.22e-03	2.04e-02	38
GO:004639422	Breast	DCIS	carboxylic acid biosynthetic process	37/1390	314/18723	3.56e-03	2.92e-02	37
GO:0006091110	Esophagus	ESCC	generation of precursor metabolites and energy	331/8552	490/18723	3.86e-23	8.45e-21	331
GO:0022900110	Esophagus	ESCC	electron transport chain	133/8552	175/18723	2.18e-16	1.67e-14	133
GO:00219159	Esophagus	ESCC	neural tube development	101/8552	152/18723	1.78e-07	2.79e-06	101
GO:00067906	Esophagus	ESCC	sulfur compound metabolic process	201/8552	339/18723	2.64e-07	3.94e-06	201
GO:00420636	Esophagus	ESCC	gliogenesis	172/8552	301/18723	3.75e-05	3.04e-04	172
GO:00086525	Esophagus	ESCC	cellular amino acid biosynthetic process	51/8552	76/18723	1.30e-04	8.88e-04	51
GO:00463948	Esophagus	ESCC	carboxylic acid biosynthetic process	175/8552	314/18723	1.98e-04	1.26e-03	175
GO:00100016	Esophagus	ESCC	glial cell differentiation	129/8552	225/18723	2.73e-04	1.65e-03	129

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0120023	Esophagus	ESCC	Carbon metabolism	79/4205	115/8465	2.50e-05	1.21e-04	6.22e-05	79
hsa0123023	Esophagus	ESCC	Biosynthesis of amino acids	49/4205	75/8465	4.35e-03	1.12e-02	5.74e-03	49
hsa0120033	Esophagus	ESCC	Carbon metabolism	79/4205	115/8465	2.50e-05	1.21e-04	6.22e-05	79
hsa0123033	Esophagus	ESCC	Biosynthesis of amino acids	49/4205	75/8465	4.35e-03	1.12e-02	5.74e-03	49
hsa0120021	Liver	Cirrhotic	Carbon metabolism	64/2530	115/8465	6.37e-09	1.18e-07	7.26e-08	64
hsa00270	Liver	Cirrhotic	Cysteine and methionine metabolism	27/2530	52/8465	6.98e-04	4.15e-03	2.56e-03	27
hsa00260	Liver	Cirrhotic	Glycine, serine and threonine metabolism	22/2530	40/8465	7.85e-04	4.51e-03	2.78e-03	22
hsa012304	Liver	Cirrhotic	Biosynthesis of amino acids	35/2530	75/8465	1.54e-03	7.83e-03	4.83e-03	35
hsa0120031	Liver	Cirrhotic	Carbon metabolism	64/2530	115/8465	6.37e-09	1.18e-07	7.26e-08	64
hsa002701	Liver	Cirrhotic	Cysteine and methionine metabolism	27/2530	52/8465	6.98e-04	4.15e-03	2.56e-03	27
hsa002601	Liver	Cirrhotic	Glycine, serine and threonine metabolism	22/2530	40/8465	7.85e-04	4.51e-03	2.78e-03	22
hsa0123011	Liver	Cirrhotic	Biosynthesis of amino acids	35/2530	75/8465	1.54e-03	7.83e-03	4.83e-03	35
hsa0120041	Liver	HCC	Carbon metabolism	89/4020	115/8465	3.92e-11	6.56e-10	3.65e-10	89
hsa0123021	Liver	HCC	Biosynthesis of amino acids	53/4020	75/8465	3.79e-05	2.11e-04	1.18e-04	53
hsa002702	Liver	HCC	Cysteine and methionine metabolism	35/4020	52/8465	3.03e-03	9.94e-03	5.53e-03	35
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
hsa0123031	Liver	HCC	Biosynthesis of amino acids	53/4020	75/8465	3.79e-05	2.11e-04	1.18e-04	53
hsa002703	Liver	HCC	Cysteine and methionine metabolism	35/4020	52/8465	3.03e-03	9.94e-03	5.53e-03	35
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

PHGDH

insertion

In_Frame_Ins

novel

c.51_52insCGTAACTTTCCAAGTCTG

p.Pro17_Cys18insArgAsnPheProSerLeu

p.P17_C18insRNFPSL

O43175

protein_coding

TCGA-A8-A06P-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unspecific

PHGDH

insertion

Nonsense_Mutation

novel

c.882_883insATAATCCCCACAGTAATGTTATGAGGGAGATAGGATCAACCCA

p.Cys295IlefsTer8

p.C295Ifs*8

O43175

protein_coding

TCGA-A8-A07J-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

PHGDH

insertion

Nonsense_Mutation

novel

c.80_81insATTTTCTTTTTGATAGTCGAATTCCCTTCAACGTCTA

p.Leu28PhefsTer4

p.L28Ffs*4

O43175

protein_coding

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PHGDH

SNV

Missense_Mutation

novel

c.686N>C

p.Val229Ala

p.V229A

O43175

protein_coding

deleterious(0)

probably_damaging(0.98)

TCGA-AA-3811-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Unknown

PHGDH

SNV

Missense_Mutation

c.1162G>A

p.Val388Met

p.V388M

O43175

protein_coding

tolerated(0.11)

benign(0.071)

TCGA-AA-A022-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

PHGDH

deletion

Frame_Shift_Del

novel

c.654delN

p.Asn218LysfsTer15

p.N218Kfs*15

O43175

protein_coding

TCGA-AY-4070-01

Colorectum

colon adenocarcinoma

Female

<65

III/IV

Chemotherapy

5-fu

PHGDH

SNV

Missense_Mutation

novel

c.625N>A

p.Leu209Ile

p.L209I

O43175

protein_coding

deleterious(0)

probably_damaging(0.992)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

PHGDH

SNV

Missense_Mutation

novel

c.764N>T

p.Ala255Val

p.A255V

O43175

protein_coding

deleterious(0.01)

possibly_damaging(0.611)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

PHGDH

SNV

Missense_Mutation

rs200693896

c.1450N>T

p.Leu484Phe

p.L484F

O43175

protein_coding

tolerated(0.06)

possibly_damaging(0.799)

TCGA-A5-A0GP-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

PHGDH

SNV

Missense_Mutation

rs142988234

c.262N>A

p.Ala88Thr

p.A88T

O43175

protein_coding

deleterious(0.02)

probably_damaging(0.997)

TCGA-A5-A1OK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

taxol

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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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