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: BAD

Gene summary for BAD

Gene summary.

Gene information	Species	Human
	Gene symbol	BAD
	Gene ID	572
	Gene name	BCL2 associated agonist of cell death
	Gene Alias	BBC2
	Cytomap	11q13.1
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	A0A024R562

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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
572	BAD	AEH-subject1	Human	Endometrium	AEH	1.11e-12	-2.60e-01	-0.3059
572	BAD	AEH-subject2	Human	Endometrium	AEH	1.95e-06	-2.58e-01	-0.2525
572	BAD	AEH-subject3	Human	Endometrium	AEH	4.47e-07	-1.68e-01	-0.2576
572	BAD	AEH-subject4	Human	Endometrium	AEH	1.47e-06	-2.53e-01	-0.2657
572	BAD	AEH-subject5	Human	Endometrium	AEH	7.79e-14	-3.91e-01	-0.2953
572	BAD	EEC-subject1	Human	Endometrium	EEC	9.41e-18	-3.33e-01	-0.2682
572	BAD	EEC-subject2	Human	Endometrium	EEC	2.85e-06	-2.21e-01	-0.2607
572	BAD	EEC-subject3	Human	Endometrium	EEC	3.83e-39	-4.12e-01	-0.2525
572	BAD	EEC-subject4	Human	Endometrium	EEC	1.48e-06	-2.43e-01	-0.2571
572	BAD	EEC-subject5	Human	Endometrium	EEC	1.26e-03	-2.44e-01	-0.249
572	BAD	GSM5276934	Human	Endometrium	EEC	1.54e-17	-3.89e-01	-0.0913
572	BAD	GSM5276937	Human	Endometrium	EEC	1.66e-10	-3.71e-01	-0.0897
572	BAD	GSM6177620_NYU_UCEC1_lib1_lib1	Human	Endometrium	EEC	1.48e-25	-4.68e-01	-0.1869
572	BAD	GSM6177620_NYU_UCEC1_lib2_lib2	Human	Endometrium	EEC	1.12e-26	-4.48e-01	-0.1875
572	BAD	GSM6177620_NYU_UCEC1_lib3_lib3	Human	Endometrium	EEC	3.24e-30	-4.48e-01	-0.1883
572	BAD	GSM6177621_NYU_UCEC2_lib1_lib1	Human	Endometrium	EEC	3.56e-32	-4.31e-01	-0.1934
572	BAD	GSM6177622_NYU_UCEC3_lib1_lib1	Human	Endometrium	EEC	8.26e-43	-4.73e-01	-0.1917
572	BAD	GSM6177622_NYU_UCEC3_lib2_lib2	Human	Endometrium	EEC	3.92e-31	-4.54e-01	-0.1916
572	BAD	GSM6177623_NYU_UCEC3_Vis	Human	Endometrium	EEC	5.00e-08	-1.52e-01	-0.1269
572	BAD	LZE4T	Human	Esophagus	ESCC	1.76e-21	6.87e-01	0.0811

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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
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
Prostate		BPH: Benign Prostatic Hyperplasia
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:000691913	Prostate	Tumor	activation of cysteine-type endopeptidase activity involved in apoptotic process	25/3246	78/18723	1.11e-03	7.12e-03	25
GO:009055915	Prostate	Tumor	regulation of membrane permeability	25/3246	78/18723	1.11e-03	7.12e-03	25
GO:000110114	Prostate	Tumor	response to acid chemical	38/3246	135/18723	1.19e-03	7.56e-03	38
GO:001605214	Prostate	Tumor	carbohydrate catabolic process	42/3246	154/18723	1.35e-03	8.44e-03	42
GO:005070814	Prostate	Tumor	regulation of protein secretion	66/3246	268/18723	1.49e-03	9.19e-03	66
GO:000697013	Prostate	Tumor	response to osmotic stress	26/3246	84/18723	1.58e-03	9.63e-03	26
GO:005071413	Prostate	Tumor	positive regulation of protein secretion	38/3246	137/18723	1.60e-03	9.71e-03	38
GO:000974916	Prostate	Tumor	response to glucose	54/3246	212/18723	1.74e-03	1.03e-02	54
GO:005086314	Prostate	Tumor	regulation of T cell activation	78/3246	329/18723	1.86e-03	1.09e-02	78
GO:003009811	Prostate	Tumor	lymphocyte differentiation	87/3246	374/18723	1.93e-03	1.12e-02	87
GO:00193187	Prostate	Tumor	hexose metabolic process	59/3246	237/18723	1.96e-03	1.14e-02	59
GO:003803411	Prostate	Tumor	signal transduction in absence of ligand	21/3246	65/18723	2.40e-03	1.35e-02	21
GO:009719211	Prostate	Tumor	extrinsic apoptotic signaling pathway in absence of ligand	21/3246	65/18723	2.40e-03	1.35e-02	21
GO:003235515	Prostate	Tumor	response to estradiol	38/3246	141/18723	2.78e-03	1.52e-02	38
GO:004561911	Prostate	Tumor	regulation of lymphocyte differentiation	45/3246	174/18723	2.93e-03	1.58e-02	45
GO:001067511	Prostate	Tumor	regulation of cellular carbohydrate metabolic process	39/3246	146/18723	2.93e-03	1.58e-02	39
GO:001090611	Prostate	Tumor	regulation of glucose metabolic process	33/3246	119/18723	3.13e-03	1.65e-02	33
GO:00059967	Prostate	Tumor	monosaccharide metabolic process	62/3246	257/18723	3.38e-03	1.75e-02	62
GO:190353211	Prostate	Tumor	positive regulation of secretion by cell	67/3246	282/18723	3.53e-03	1.82e-02	67
GO:190210712	Prostate	Tumor	positive regulation of leukocyte differentiation	41/3246	157/18723	3.63e-03	1.86e-02	41

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0502020	Endometrium	AEH	Prion disease	110/1197	273/8465	2.39e-27	2.44e-25	1.78e-25	110
hsa0520826	Endometrium	AEH	Chemical carcinogenesis - reactive oxygen species	91/1197	223/8465	3.28e-23	1.33e-21	9.76e-22	91
hsa0501420	Endometrium	AEH	Amyotrophic lateral sclerosis	123/1197	364/8465	2.17e-22	7.82e-21	5.72e-21	123
hsa0501020	Endometrium	AEH	Alzheimer disease	124/1197	384/8465	1.20e-20	3.91e-19	2.86e-19	124
hsa0502220	Endometrium	AEH	Pathways of neurodegeneration - multiple diseases	137/1197	476/8465	9.27e-18	2.32e-16	1.70e-16	137
hsa0451015	Endometrium	AEH	Focal adhesion	58/1197	203/8465	4.99e-08	7.37e-07	5.39e-07	58
hsa0472216	Endometrium	AEH	Neurotrophin signaling pathway	31/1197	119/8465	4.07e-04	3.07e-03	2.25e-03	31
hsa0491920	Endometrium	AEH	Thyroid hormone signaling pathway	30/1197	121/8465	1.20e-03	7.52e-03	5.50e-03	30
hsa0541726	Endometrium	AEH	Lipid and atherosclerosis	47/1197	215/8465	1.24e-03	7.62e-03	5.58e-03	47
hsa052158	Endometrium	AEH	Prostate cancer	25/1197	97/8465	1.68e-03	1.01e-02	7.39e-03	25
hsa0421010	Endometrium	AEH	Apoptosis	30/1197	136/8465	7.72e-03	4.05e-02	2.96e-02	30
hsa0517018	Endometrium	AEH	Human immunodeficiency virus 1 infection	43/1197	212/8465	8.19e-03	4.22e-02	3.09e-02	43
hsa05020110	Endometrium	AEH	Prion disease	110/1197	273/8465	2.39e-27	2.44e-25	1.78e-25	110
hsa05208112	Endometrium	AEH	Chemical carcinogenesis - reactive oxygen species	91/1197	223/8465	3.28e-23	1.33e-21	9.76e-22	91
hsa05014110	Endometrium	AEH	Amyotrophic lateral sclerosis	123/1197	364/8465	2.17e-22	7.82e-21	5.72e-21	123
hsa05010110	Endometrium	AEH	Alzheimer disease	124/1197	384/8465	1.20e-20	3.91e-19	2.86e-19	124
hsa05022110	Endometrium	AEH	Pathways of neurodegeneration - multiple diseases	137/1197	476/8465	9.27e-18	2.32e-16	1.70e-16	137
hsa0451016	Endometrium	AEH	Focal adhesion	58/1197	203/8465	4.99e-08	7.37e-07	5.39e-07	58
hsa0472217	Endometrium	AEH	Neurotrophin signaling pathway	31/1197	119/8465	4.07e-04	3.07e-03	2.25e-03	31
hsa04919110	Endometrium	AEH	Thyroid hormone signaling pathway	30/1197	121/8465	1.20e-03	7.52e-03	5.50e-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

TF	Cell Type	Tissue	Disease Stage	Target Gene	RSS	Regulon Activity
BAD	MYOFIB	Esophagus	ADJ	FIBCD1,SLC22A23,S100A3, etc.	0.00e+00
BAD	INCAF	Esophagus	ADJ	FIBCD1,SLC22A23,S100A3, etc.	0.00e+00
BAD	SMC	Esophagus	ESCC	FIBCD1,SLC22A23,S100A3, etc.	5.49e-03
BAD	FIB	Esophagus	ESCC	FIBCD1,SLC22A23,S100A3, etc.	0.00e+00

∗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

BAD

SNV

Missense_Mutation

c.351G>A

p.Met117Ile

p.M117I

Q92934

protein_coding

deleterious(0)

probably_damaging(0.966)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

BAD

SNV

Missense_Mutation

c.293N>A

p.Arg98His

p.R98H

Q92934

protein_coding

deleterious(0.03)

possibly_damaging(0.688)

TCGA-EK-A2RK-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

BAD

SNV

Missense_Mutation

c.57G>C

p.Glu19Asp

p.E19D

Q92934

protein_coding

tolerated_low_confidence(1)

benign(0.001)

TCGA-4N-A93T-01

Colorectum

colon adenocarcinoma

Male

>=65

III/IV

Chemotherapy

xeloda

BAD

SNV

Missense_Mutation

rs775688969

c.74N>A

p.Ser25Asn

p.S25N

Q92934

protein_coding

tolerated(0.13)

benign(0.409)

TCGA-AA-A010-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Chemotherapy

folinic

BAD

SNV

Missense_Mutation

novel

c.212G>T

p.Ser71Ile

p.S71I

Q92934

protein_coding

deleterious(0.01)

possibly_damaging(0.857)

TCGA-AJ-A5DW-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

BAD

SNV

Missense_Mutation

novel

c.401N>T

p.Ser134Ile

p.S134I

Q92934

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-AX-A1CE-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

BAD

SNV

Missense_Mutation

novel

c.485N>A

p.Gly162Glu

p.G162E

Q92934

protein_coding

deleterious_low_confidence(0)

probably_damaging(1)

TCGA-AX-A2HC-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

BAD

SNV

Missense_Mutation

c.298N>A

p.Ala100Thr

p.A100T

Q92934

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-D1-A17R-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

BAD

SNV

Missense_Mutation

c.128G>A

p.Gly43Asp

p.G43D

Q92934

protein_coding

tolerated(0.08)

probably_damaging(1)

TCGA-FI-A2D5-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

carboplatinum

BAD

SNV

Missense_Mutation

c.483N>T

p.Arg161Ser

p.R161S

Q92934

protein_coding

deleterious_low_confidence(0)

benign(0.272)

TCGA-CH-5739-01

Prostate

prostate adenocarcinoma

Male

>=65

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
572	BAD	KINASE, DRUGGABLE GENOME		RUBOXISTAURIN	RUBOXISTAURIN	18077363
572	BAD	KINASE, DRUGGABLE GENOME		AT-101	ISOSORBIDE

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