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: CTH

Gene summary for CTH

Gene summary.

Gene information	Species	Human
	Gene symbol	CTH
	Gene ID	1491
	Gene name	cystathionine gamma-lyase
	Gene Alias	CSE
	Cytomap	1p31.1
	Gene Type	protein-coding
	GO ID	GO:0000096
	UniProtAcc	P32929

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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
1491	CTH	S41	Human	Liver	Cirrhotic	1.61e-07	8.94e-01	-0.0343
1491	CTH	S44	Human	Liver	HCC	8.29e-03	7.79e-01	-0.0083
1491	CTH	HCC1_Meng	Human	Liver	HCC	1.36e-58	7.04e-02	0.0246
1491	CTH	S029	Human	Liver	HCC	2.22e-02	5.68e-01	0.2581

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Liver		HCC: Hepatocellular carcinoma
Liver		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:004339327	Thyroid	ATC	regulation of protein binding	110/6293	196/18723	6.99e-11	2.22e-09	110
GO:006082825	Thyroid	ATC	regulation of canonical Wnt signaling pathway	134/6293	253/18723	1.49e-10	4.56e-09	134
GO:006007025	Thyroid	ATC	canonical Wnt signaling pathway	154/6293	303/18723	3.68e-10	1.02e-08	154
GO:000164932	Thyroid	ATC	osteoblast differentiation	122/6293	229/18723	6.04e-10	1.60e-08	122
GO:006056222	Thyroid	ATC	epithelial tube morphogenesis	156/6293	325/18723	4.48e-08	8.14e-07	156
GO:003209224	Thyroid	ATC	positive regulation of protein binding	53/6293	85/18723	5.37e-08	9.67e-07	53
GO:000184119	Thyroid	ATC	neural tube formation	59/6293	102/18723	4.28e-07	6.25e-06	59
GO:002191515	Thyroid	ATC	neural tube development	80/6293	152/18723	9.87e-07	1.29e-05	80
GO:000183823	Thyroid	ATC	embryonic epithelial tube formation	65/6293	121/18723	4.02e-06	4.43e-05	65
GO:001402017	Thyroid	ATC	primary neural tube formation	53/6293	94/18723	4.69e-06	5.11e-05	53
GO:000184316	Thyroid	ATC	neural tube closure	50/6293	88/18723	6.43e-06	6.68e-05	50
GO:003017815	Thyroid	ATC	negative regulation of Wnt signaling pathway	85/6293	170/18723	6.94e-06	7.16e-05	85
GO:006060616	Thyroid	ATC	tube closure	50/6293	89/18723	9.90e-06	9.87e-05	50
GO:007217522	Thyroid	ATC	epithelial tube formation	68/6293	132/18723	1.59e-05	1.48e-04	68
GO:001633114	Thyroid	ATC	morphogenesis of embryonic epithelium	74/6293	147/18723	1.96e-05	1.77e-04	74
GO:003514823	Thyroid	ATC	tube formation	74/6293	148/18723	2.65e-05	2.27e-04	74
GO:004566721	Thyroid	ATC	regulation of osteoblast differentiation	66/6293	132/18723	7.03e-05	5.36e-04	66
GO:004566912	Thyroid	ATC	positive regulation of osteoblast differentiation	38/6293	69/18723	1.97e-04	1.31e-03	38
GO:009009014	Thyroid	ATC	negative regulation of canonical Wnt signaling pathway	66/6293	137/18723	2.82e-04	1.80e-03	66
GO:00487715	Thyroid	ATC	tissue remodeling	78/6293	175/18723	1.60e-03	8.04e-03	78

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
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
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
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
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

CTH

SNV

Missense_Mutation

c.592N>A

p.Pro198Thr

p.P198T

P32929

protein_coding

deleterious(0.01)

probably_damaging(0.993)

TCGA-D8-A1JD-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

CTH

SNV

Missense_Mutation

novel

c.598N>T

p.Ala200Ser

p.A200S

P32929

protein_coding

tolerated(0.67)

benign(0)

TCGA-E9-A295-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

CTH

insertion

Frame_Shift_Ins

novel

c.1119_1120insCTAGTTTTTTCAAAGC

p.Ile374LeufsTer15

p.I374Lfs*15

P32929

protein_coding

TCGA-A8-A09D-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

CTH

insertion

Frame_Shift_Ins

novel

c.1121_1122insCAGAGGATATTGGTACAAGAAGCAG

p.Leu376GlyfsTer16

p.L376Gfs*16

P32929

protein_coding

TCGA-A8-A09D-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

CTH

SNV

Missense_Mutation

rs866702899

c.469G>A

p.Glu157Lys

p.E157K

P32929

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-FU-A3HZ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

CTH

SNV

Missense_Mutation

novel

c.979N>C

p.Ile327Leu

p.I327L

P32929

protein_coding

tolerated(0.23)

benign(0)

TCGA-CA-6717-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Chemotherapy

oxaliplatin

CTH

SNV

Missense_Mutation

c.241N>A

p.Ala81Thr

p.A81T

P32929

protein_coding

deleterious(0)

probably_damaging(0.982)

TCGA-D5-6930-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

CTH

SNV

Missense_Mutation

novel

c.1124N>A

p.Arg375Gln

p.R375Q

P32929

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-EI-6917-01

Colorectum

rectum adenocarcinoma

Male

<65

III/IV

Chemotherapy

5fluorouracil+oxaciplatina+l-folinian

CTH

SNV

Missense_Mutation

novel

c.626N>A

p.Ser209Tyr

p.S209Y

P32929

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-A5-A2K5-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

CTH

SNV

Missense_Mutation

novel

c.1177N>A

p.Ala393Thr

p.A393T

P32929

protein_coding

deleterious(0.01)

probably_damaging(0.997)

TCGA-AP-A1DV-01

Endometrium

uterine corpus endometrioid carcinoma

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
1491	CTH	ENZYME		busulfan	BUSULFAN	27779248
1491	CTH	ENZYME		Hydrazinoacetic acid
1491	CTH	ENZYME		cyclophosphamide	CYCLOPHOSPHAMIDE	27779248
1491	CTH	ENZYME	inhibitor	178101828
1491	CTH	ENZYME		AKOS003197197
1491	CTH	ENZYME	inhibitor	252827517	AMINOETHOXYVINYLGLYCINE
1491	CTH	ENZYME	inhibitor	252827516
1491	CTH	ENZYME	inhibitor	178101931
1491	CTH	ENZYME		5-Hydrazino-1H-tetrazole

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