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: BCAT1

Gene summary for BCAT1

Gene summary.

Gene information	Species	Human
	Gene symbol	BCAT1
	Gene ID	586
	Gene name	branched chain amino acid transaminase 1
	Gene Alias	BCATC
	Cytomap	12p12.1
	Gene Type	protein-coding
	GO ID	GO:0000082
	UniProtAcc	P54687

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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
586	BCAT1	EEC-subject2	Human	Endometrium	EEC	4.09e-09	4.32e-01	-0.2607
586	BCAT1	EEC-subject3	Human	Endometrium	EEC	5.60e-04	-1.24e-01	-0.2525
586	BCAT1	GSM5276935	Human	Endometrium	EEC	4.85e-22	6.15e-01	-0.123
586	BCAT1	GSM6177620_NYU_UCEC1_lib1_lib1	Human	Endometrium	EEC	3.08e-34	9.65e-01	-0.1869
586	BCAT1	GSM6177620_NYU_UCEC1_lib2_lib2	Human	Endometrium	EEC	3.87e-26	8.46e-01	-0.1875
586	BCAT1	GSM6177620_NYU_UCEC1_lib3_lib3	Human	Endometrium	EEC	7.82e-33	8.57e-01	-0.1883
586	BCAT1	GSM6177621_NYU_UCEC2_lib1_lib1	Human	Endometrium	EEC	5.82e-11	4.04e-01	-0.1934
586	BCAT1	GSM6177622_NYU_UCEC3_lib1_lib1	Human	Endometrium	EEC	2.23e-48	9.99e-01	-0.1917
586	BCAT1	GSM6177622_NYU_UCEC3_lib2_lib2	Human	Endometrium	EEC	9.91e-33	8.38e-01	-0.1916
586	BCAT1	GSM6177623_NYU_UCEC3_Vis	Human	Endometrium	EEC	5.36e-30	7.87e-01	-0.1269
586	BCAT1	LZE7T	Human	Esophagus	ESCC	1.48e-05	8.04e-01	0.0667
586	BCAT1	P2T-E	Human	Esophagus	ESCC	3.48e-33	6.32e-01	0.1177
586	BCAT1	P4T-E	Human	Esophagus	ESCC	4.07e-18	5.40e-01	0.1323
586	BCAT1	P5T-E	Human	Esophagus	ESCC	1.98e-18	4.66e-01	0.1327
586	BCAT1	P12T-E	Human	Esophagus	ESCC	8.01e-03	2.32e-01	0.1122
586	BCAT1	P15T-E	Human	Esophagus	ESCC	2.02e-03	2.49e-01	0.1149
586	BCAT1	P16T-E	Human	Esophagus	ESCC	4.39e-17	3.29e-01	0.1153
586	BCAT1	P23T-E	Human	Esophagus	ESCC	2.64e-07	2.20e-01	0.108
586	BCAT1	P24T-E	Human	Esophagus	ESCC	3.29e-07	1.78e-01	0.1287
586	BCAT1	P26T-E	Human	Esophagus	ESCC	3.69e-22	5.39e-01	0.1276

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
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:004477213	Endometrium	EEC	mitotic cell cycle phase transition	71/2168	424/18723	8.68e-04	7.97e-03	71
GO:004477216	Esophagus	ESCC	mitotic cell cycle phase transition	281/8552	424/18723	4.63e-18	4.45e-16	281
GO:000008214	Esophagus	ESCC	G1/S transition of mitotic cell cycle	134/8552	214/18723	4.04e-07	5.55e-06	134
GO:004484314	Esophagus	ESCC	cell cycle G1/S phase transition	148/8552	241/18723	5.68e-07	7.48e-06	148
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:00160538	Esophagus	ESCC	organic acid biosynthetic process	175/8552	316/18723	3.04e-04	1.82e-03	175
GO:00090815	Esophagus	ESCC	branched-chain amino acid metabolic process	14/8552	19/18723	1.27e-02	4.21e-02	14
GO:00447723	Lung	IAC	mitotic cell cycle phase transition	85/2061	424/18723	2.69e-08	3.20e-06	85
GO:00000823	Lung	IAC	G1/S transition of mitotic cell cycle	46/2061	214/18723	6.13e-06	2.29e-04	46
GO:00448433	Lung	IAC	cell cycle G1/S phase transition	49/2061	241/18723	1.54e-05	4.49e-04	49
GO:004477211	Lung	AIS	mitotic cell cycle phase transition	69/1849	424/18723	2.23e-05	7.42e-04	69
GO:000008211	Lung	AIS	G1/S transition of mitotic cell cycle	37/1849	214/18723	5.26e-04	8.42e-03	37
GO:004484311	Lung	AIS	cell cycle G1/S phase transition	40/1849	241/18723	7.43e-04	1.07e-02	40
GO:004477221	Lung	MIAC	mitotic cell cycle phase transition	41/967	424/18723	8.79e-05	3.92e-03	41
GO:00447728	Oral cavity	OSCC	mitotic cell cycle phase transition	255/7305	424/18723	5.29e-19	6.98e-17	255
GO:00000826	Oral cavity	OSCC	G1/S transition of mitotic cell cycle	120/7305	214/18723	2.86e-07	4.40e-06	120
GO:00448436	Oral cavity	OSCC	cell cycle G1/S phase transition	131/7305	241/18723	8.77e-07	1.20e-05	131
GO:00160537	Oral cavity	OSCC	organic acid biosynthetic process	155/7305	316/18723	1.64e-04	1.13e-03	155
GO:00463947	Oral cavity	OSCC	carboxylic acid biosynthetic process	154/7305	314/18723	1.73e-04	1.19e-03	154

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa002704	Endometrium	EEC	Cysteine and methionine metabolism	15/1237	52/8465	6.02e-03	3.12e-02	2.33e-02	15
hsa0027011	Endometrium	EEC	Cysteine and methionine metabolism	15/1237	52/8465	6.02e-03	3.12e-02	2.33e-02	15
hsa012405	Esophagus	ESCC	Biosynthesis of cofactors	97/4205	153/8465	3.88e-04	1.35e-03	6.94e-04	97
hsa002809	Esophagus	ESCC	Valine, leucine and isoleucine degradation	34/4205	48/8465	2.34e-03	6.54e-03	3.35e-03	34
hsa0123023	Esophagus	ESCC	Biosynthesis of amino acids	49/4205	75/8465	4.35e-03	1.12e-02	5.74e-03	49
hsa0124012	Esophagus	ESCC	Biosynthesis of cofactors	97/4205	153/8465	3.88e-04	1.35e-03	6.94e-04	97
hsa0028014	Esophagus	ESCC	Valine, leucine and isoleucine degradation	34/4205	48/8465	2.34e-03	6.54e-03	3.35e-03	34
hsa0123033	Esophagus	ESCC	Biosynthesis of amino acids	49/4205	75/8465	4.35e-03	1.12e-02	5.74e-03	49
hsa012404	Oral cavity	OSCC	Biosynthesis of cofactors	88/3704	153/8465	3.84e-04	1.20e-03	6.12e-04	88
hsa012305	Oral cavity	OSCC	Biosynthesis of amino acids	45/3704	75/8465	3.27e-03	8.23e-03	4.19e-03	45
hsa002808	Oral cavity	OSCC	Valine, leucine and isoleucine degradation	30/3704	48/8465	6.75e-03	1.57e-02	7.99e-03	30
hsa0124011	Oral cavity	OSCC	Biosynthesis of cofactors	88/3704	153/8465	3.84e-04	1.20e-03	6.12e-04	88
hsa0123012	Oral cavity	OSCC	Biosynthesis of amino acids	45/3704	75/8465	3.27e-03	8.23e-03	4.19e-03	45
hsa0028013	Oral cavity	OSCC	Valine, leucine and isoleucine degradation	30/3704	48/8465	6.75e-03	1.57e-02	7.99e-03	30

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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

BCAT1

SNV

Missense_Mutation

c.89N>T

p.Ser30Leu

p.S30L

P54687

protein_coding

tolerated(0.06)

benign(0.001)

TCGA-A8-A0A7-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

BCAT1

SNV

Missense_Mutation

c.875C>T

p.Pro292Leu

p.P292L

P54687

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-B6-A1KN-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

BCAT1

SNV

Missense_Mutation

rs766214085

c.524G>A

p.Arg175His

p.R175H

P54687

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-D8-A1XQ-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

BCAT1

SNV

Missense_Mutation

c.1187N>C

p.Val396Ala

p.V396A

P54687

protein_coding

deleterious(0.03)

benign(0.099)

TCGA-E2-A150-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

BCAT1

SNV

Missense_Mutation

rs377651136

c.1127G>A

p.Arg376His

p.R376H

P54687

protein_coding

deleterious(0)

possibly_damaging(0.88)

TCGA-E2-A15K-06

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

BCAT1

insertion

Frame_Shift_Ins

novel

c.784_785insATAGGAGGTATAAACAGAGTTCTTTCGGTAATAGCCTGCCGTCT

p.Gly262AspfsTer27

p.G262Dfs*27

P54687

protein_coding

TCGA-A8-A09B-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

5-fluorouracil

BCAT1

insertion

Nonsense_Mutation

novel

c.731_732insAATGTATCCAAGGAATACATAA

p.Phe244LeufsTer8

p.F244Lfs*8

P54687

protein_coding

TCGA-AO-A0J5-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Other, specify in notesBisphosphonate

zoledronic

BCAT1

SNV

Missense_Mutation

novel

c.79G>C

p.Glu27Gln

p.E27Q

P54687

protein_coding

tolerated(0.36)

benign(0.154)

TCGA-C5-A8XJ-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

cisplatin

BCAT1

SNV

Missense_Mutation

c.576A>C

p.Lys192Asn

p.K192N

P54687

protein_coding

tolerated(0.08)

benign(0.03)

TCGA-AA-3492-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

BCAT1

SNV

Missense_Mutation

c.125N>C

p.Leu42Pro

p.L42P

P54687

protein_coding

deleterious(0)

probably_damaging(0.992)

TCGA-AA-3502-01

Colorectum

colon adenocarcinoma

Male

>=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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