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: SHMT2

Gene summary for SHMT2

Gene summary.

Gene information	Species	Human
	Gene symbol	SHMT2
	Gene ID	6472
	Gene name	serine hydroxymethyltransferase 2
	Gene Alias	GLYA
	Cytomap	12q13.3
	Gene Type	protein-coding
	GO ID	GO:0002082
	UniProtAcc	P34897

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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
6472	SHMT2	HTA11_3410_2000001011	Human	Colorectum	AD	9.84e-06	1.53e-01	0.0155
6472	SHMT2	HTA11_2487_2000001011	Human	Colorectum	SER	2.44e-05	2.69e-01	-0.1808
6472	SHMT2	HTA11_2951_2000001011	Human	Colorectum	AD	3.40e-02	1.87e-01	0.0216
6472	SHMT2	HTA11_1938_2000001011	Human	Colorectum	AD	4.00e-12	3.35e-01	-0.0811
6472	SHMT2	HTA11_78_2000001011	Human	Colorectum	AD	8.38e-10	2.29e-01	-0.1088
6472	SHMT2	HTA11_347_2000001011	Human	Colorectum	AD	6.35e-08	2.04e-01	-0.1954
6472	SHMT2	HTA11_3361_2000001011	Human	Colorectum	AD	4.57e-06	2.62e-01	-0.1207
6472	SHMT2	HTA11_696_2000001011	Human	Colorectum	AD	8.44e-12	2.63e-01	-0.1464
6472	SHMT2	HTA11_866_2000001011	Human	Colorectum	AD	9.63e-08	2.11e-01	-0.1001
6472	SHMT2	HTA11_1391_2000001011	Human	Colorectum	AD	1.17e-15	3.77e-01	-0.059
6472	SHMT2	HTA11_546_2000001011	Human	Colorectum	AD	1.56e-06	2.54e-01	-0.0842
6472	SHMT2	HTA11_9341_2000001011	Human	Colorectum	SER	1.86e-06	3.98e-01	-0.00410000000000005
6472	SHMT2	HTA11_7862_2000001011	Human	Colorectum	AD	1.96e-03	1.92e-01	-0.0179
6472	SHMT2	HTA11_866_3004761011	Human	Colorectum	AD	3.09e-24	4.90e-01	0.096
6472	SHMT2	HTA11_4255_2000001011	Human	Colorectum	SER	2.17e-09	4.60e-01	0.0446
6472	SHMT2	HTA11_9408_2000001011	Human	Colorectum	AD	9.81e-03	2.64e-01	0.0451
6472	SHMT2	HTA11_8622_2000001021	Human	Colorectum	SER	8.41e-15	5.55e-01	0.0528
6472	SHMT2	HTA11_7663_2000001011	Human	Colorectum	SER	7.26e-05	2.78e-01	0.0131
6472	SHMT2	HTA11_10623_2000001011	Human	Colorectum	AD	1.29e-08	3.12e-01	-0.0177
6472	SHMT2	HTA11_6801_2000001011	Human	Colorectum	SER	1.64e-05	4.64e-01	0.0171

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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
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:0046034	Colorectum	AD	ATP metabolic process	142/3918	277/18723	2.64e-29	8.26e-26	142
GO:0006091	Colorectum	AD	generation of precursor metabolites and energy	209/3918	490/18723	3.17e-28	6.61e-25	209
GO:0009060	Colorectum	AD	aerobic respiration	108/3918	189/18723	9.14e-28	1.43e-24	108
GO:0045333	Colorectum	AD	cellular respiration	119/3918	230/18723	3.21e-25	4.02e-22	119
GO:0006119	Colorectum	AD	oxidative phosphorylation	83/3918	141/18723	7.95e-23	8.30e-20	83
GO:0015980	Colorectum	AD	energy derivation by oxidation of organic compounds	143/3918	318/18723	2.78e-22	2.49e-19	143
GO:0072521	Colorectum	AD	purine-containing compound metabolic process	153/3918	416/18723	4.34e-14	1.01e-11	153
GO:0044282	Colorectum	AD	small molecule catabolic process	118/3918	376/18723	1.05e-06	3.55e-05	118
GO:0006417	Colorectum	AD	regulation of translation	141/3918	468/18723	1.32e-06	4.22e-05	141
GO:0043467	Colorectum	AD	regulation of generation of precursor metabolites and energy	49/3918	130/18723	8.33e-06	1.99e-04	49
GO:0072522	Colorectum	AD	purine-containing compound biosynthetic process	68/3918	200/18723	1.12e-05	2.55e-04	68
GO:1903578	Colorectum	AD	regulation of ATP metabolic process	34/3918	87/18723	8.30e-05	1.30e-03	34
GO:0016054	Colorectum	AD	organic acid catabolic process	73/3918	240/18723	3.20e-04	3.81e-03	73
GO:0006575	Colorectum	AD	cellular modified amino acid metabolic process	59/3918	188/18723	4.80e-04	5.27e-03	59
GO:0006730	Colorectum	AD	one-carbon metabolic process	18/3918	40/18723	5.36e-04	5.74e-03	18
GO:0043648	Colorectum	AD	dicarboxylic acid metabolic process	34/3918	96/18723	7.22e-04	7.28e-03	34
GO:0046395	Colorectum	AD	carboxylic acid catabolic process	70/3918	236/18723	9.06e-04	8.71e-03	70
GO:0043457	Colorectum	AD	regulation of cellular respiration	20/3918	49/18723	1.23e-03	1.09e-02	20
GO:1903715	Colorectum	AD	regulation of aerobic respiration	15/3918	33/18723	1.36e-03	1.18e-02	15
GO:0006520	Colorectum	AD	cellular amino acid metabolic process	81/3918	284/18723	1.37e-03	1.19e-02	81

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa01200	Colorectum	AD	Carbon metabolism	55/2092	115/8465	5.53e-08	8.42e-07	5.37e-07	55
hsa00630	Colorectum	AD	Glyoxylate and dicarboxylate metabolism	14/2092	30/8465	7.25e-03	2.97e-02	1.89e-02	14
hsa01230	Colorectum	AD	Biosynthesis of amino acids	28/2092	75/8465	9.99e-03	3.89e-02	2.48e-02	28
hsa012001	Colorectum	AD	Carbon metabolism	55/2092	115/8465	5.53e-08	8.42e-07	5.37e-07	55
hsa006301	Colorectum	AD	Glyoxylate and dicarboxylate metabolism	14/2092	30/8465	7.25e-03	2.97e-02	1.89e-02	14
hsa012301	Colorectum	AD	Biosynthesis of amino acids	28/2092	75/8465	9.99e-03	3.89e-02	2.48e-02	28
hsa012002	Colorectum	SER	Carbon metabolism	40/1580	115/8465	2.77e-05	3.41e-04	2.47e-04	40
hsa012302	Colorectum	SER	Biosynthesis of amino acids	23/1580	75/8465	8.11e-03	4.14e-02	3.01e-02	23
hsa012003	Colorectum	SER	Carbon metabolism	40/1580	115/8465	2.77e-05	3.41e-04	2.47e-04	40
hsa012303	Colorectum	SER	Biosynthesis of amino acids	23/1580	75/8465	8.11e-03	4.14e-02	3.01e-02	23
hsa012004	Colorectum	MSS	Carbon metabolism	43/1875	115/8465	1.37e-04	1.17e-03	7.19e-04	43
hsa012005	Colorectum	MSS	Carbon metabolism	43/1875	115/8465	1.37e-04	1.17e-03	7.19e-04	43
hsa00670	Colorectum	MSI-H	One carbon pool by folate	7/797	20/8465	1.65e-03	1.73e-02	1.45e-02	7
hsa006701	Colorectum	MSI-H	One carbon pool by folate	7/797	20/8465	1.65e-03	1.73e-02	1.45e-02	7
hsa0120023	Esophagus	ESCC	Carbon metabolism	79/4205	115/8465	2.50e-05	1.21e-04	6.22e-05	79
hsa012405	Esophagus	ESCC	Biosynthesis of cofactors	97/4205	153/8465	3.88e-04	1.35e-03	6.94e-04	97
hsa0123023	Esophagus	ESCC	Biosynthesis of amino acids	49/4205	75/8465	4.35e-03	1.12e-02	5.74e-03	49
hsa015232	Esophagus	ESCC	Antifolate resistance	22/4205	30/8465	7.23e-03	1.76e-02	8.99e-03	22
hsa006306	Esophagus	ESCC	Glyoxylate and dicarboxylate metabolism	21/4205	30/8465	1.95e-02	4.35e-02	2.23e-02	21
hsa0120033	Esophagus	ESCC	Carbon metabolism	79/4205	115/8465	2.50e-05	1.21e-04	6.22e-05	79

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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

SHMT2

SNV

Missense_Mutation

c.1442G>T

p.Arg481Leu

p.R481L

P34897

protein_coding

deleterious(0.05)

benign(0.035)

TCGA-AQ-A54N-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SHMT2

SNV

Missense_Mutation

c.814G>A

p.Asp272Asn

p.D272N

P34897

protein_coding

deleterious(0)

probably_damaging(0.975)

TCGA-BH-A0B9-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

SHMT2

SNV

Missense_Mutation

c.799N>G

p.Pro267Ala

p.P267A

P34897

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-D8-A1J9-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SHMT2

SNV

Missense_Mutation

c.711N>A

p.Met237Ile

p.M237I

P34897

protein_coding

tolerated(0.24)

benign(0.005)

TCGA-D8-A1JN-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

anastrozolum

SHMT2

insertion

Nonsense_Mutation

novel

c.771_772insGTCCATCTTCTTCGAGTCTATGCCCTATAAG

p.Leu258ValfsTer10

p.L258Vfs*10

P34897

protein_coding

TCGA-A8-A09W-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

SHMT2

deletion

Frame_Shift_Del

c.601delA

p.Thr201LeufsTer11

p.T201Lfs*11

P34897

protein_coding

TCGA-BH-A0HA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SHMT2

SNV

Missense_Mutation

novel

c.266G>T

p.Gly89Val

p.G89V

P34897

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-EK-A2PL-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unknown

SHMT2

SNV

Missense_Mutation

c.328N>C

p.Glu110Gln

p.E110Q

P34897

protein_coding

tolerated(0.14)

benign(0.21)

TCGA-Q1-A73O-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SHMT2

SNV

Missense_Mutation

novel

c.523N>A

p.Gly175Ser

p.G175S

P34897

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AA-3877-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

SHMT2

SNV

Missense_Mutation

c.1075C>T

p.Arg359Trp

p.R359W

P34897

protein_coding

deleterious(0)

possibly_damaging(0.609)

TCGA-CK-4951-01

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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