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: BID

Gene summary for BID

Gene summary.

Gene information	Species	Human
	Gene symbol	BID
	Gene ID	637
	Gene name	BH3 interacting domain death agonist
	Gene Alias	FP497
	Cytomap	22q11.21
	Gene Type	protein-coding
	GO ID	GO:0000082
	UniProtAcc	A8ASI8

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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
637	BID	LZE2T	Human	Esophagus	ESCC	4.91e-04	6.56e-01	0.082
637	BID	LZE4T	Human	Esophagus	ESCC	5.17e-10	3.11e-01	0.0811
637	BID	LZE5T	Human	Esophagus	ESCC	3.09e-02	6.36e-01	0.0514
637	BID	LZE7T	Human	Esophagus	ESCC	3.90e-11	8.68e-01	0.0667
637	BID	LZE8T	Human	Esophagus	ESCC	3.16e-07	4.80e-01	0.067
637	BID	LZE20T	Human	Esophagus	ESCC	1.17e-11	4.39e-01	0.0662
637	BID	LZE22D1	Human	Esophagus	HGIN	1.12e-02	9.80e-02	0.0595
637	BID	LZE22T	Human	Esophagus	ESCC	2.26e-02	6.16e-01	0.068
637	BID	LZE24T	Human	Esophagus	ESCC	4.13e-17	6.67e-01	0.0596
637	BID	LZE21T	Human	Esophagus	ESCC	3.07e-05	4.64e-01	0.0655
637	BID	P2T-E	Human	Esophagus	ESCC	6.70e-32	7.10e-01	0.1177
637	BID	P4T-E	Human	Esophagus	ESCC	5.72e-45	1.38e+00	0.1323
637	BID	P5T-E	Human	Esophagus	ESCC	1.50e-63	1.42e+00	0.1327
637	BID	P8T-E	Human	Esophagus	ESCC	1.06e-35	9.84e-01	0.0889
637	BID	P9T-E	Human	Esophagus	ESCC	2.02e-27	8.67e-01	0.1131
637	BID	P10T-E	Human	Esophagus	ESCC	9.82e-44	8.30e-01	0.116
637	BID	P11T-E	Human	Esophagus	ESCC	1.92e-09	4.86e-01	0.1426
637	BID	P12T-E	Human	Esophagus	ESCC	2.40e-27	6.43e-01	0.1122
637	BID	P15T-E	Human	Esophagus	ESCC	1.66e-28	8.13e-01	0.1149
637	BID	P16T-E	Human	Esophagus	ESCC	3.80e-29	7.91e-01	0.1153

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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:000008221	Oral cavity	EOLP	G1/S transition of mitotic cell cycle	46/2218	214/18723	4.02e-05	5.51e-04	46
GO:002240918	Oral cavity	EOLP	positive regulation of cell-cell adhesion	57/2218	284/18723	4.23e-05	5.77e-04	57
GO:007058523	Oral cavity	EOLP	protein localization to mitochondrion	31/2218	125/18723	4.36e-05	5.88e-04	31
GO:00022633	Oral cavity	EOLP	cell activation involved in immune response	56/2218	279/18723	4.91e-05	6.47e-04	56
GO:001082123	Oral cavity	EOLP	regulation of mitochondrion organization	34/2218	144/18723	5.63e-05	7.18e-04	34
GO:00023662	Oral cavity	EOLP	leukocyte activation involved in immune response	55/2218	275/18723	6.32e-05	7.90e-04	55
GO:00022852	Oral cavity	EOLP	lymphocyte activation involved in immune response	42/2218	194/18723	7.17e-05	8.82e-04	42
GO:000734621	Oral cavity	EOLP	regulation of mitotic cell cycle	82/2218	457/18723	7.50e-05	9.14e-04	82
GO:0046637	Oral cavity	EOLP	regulation of alpha-beta T cell differentiation	20/2218	68/18723	7.88e-05	9.51e-04	20
GO:000611925	Oral cavity	EOLP	oxidative phosphorylation	33/2218	141/18723	8.63e-05	1.02e-03	33
GO:002290425	Oral cavity	EOLP	respiratory electron transport chain	28/2218	114/18723	1.20e-04	1.33e-03	28
GO:007265523	Oral cavity	EOLP	establishment of protein localization to mitochondrion	29/2218	120/18723	1.24e-04	1.37e-03	29
GO:000863023	Oral cavity	EOLP	intrinsic apoptotic signaling pathway in response to DNA damage	25/2218	99/18723	1.70e-04	1.78e-03	25
GO:000698422	Oral cavity	EOLP	ER-nucleus signaling pathway	15/2218	46/18723	1.71e-04	1.78e-03	15
GO:0043370	Oral cavity	EOLP	regulation of CD4-positive, alpha-beta T cell differentiation	16/2218	51/18723	1.75e-04	1.80e-03	16
GO:00455803	Oral cavity	EOLP	regulation of T cell differentiation	33/2218	146/18723	1.75e-04	1.81e-03	33
GO:000906025	Oral cavity	EOLP	aerobic respiration	40/2218	189/18723	1.76e-04	1.81e-03	40
GO:00508514	Oral cavity	EOLP	antigen receptor-mediated signaling pathway	48/2218	240/18723	1.79e-04	1.84e-03	48
GO:190210713	Oral cavity	EOLP	positive regulation of leukocyte differentiation	34/2218	157/18723	3.32e-04	3.08e-03	34
GO:190370813	Oral cavity	EOLP	positive regulation of hemopoiesis	34/2218	157/18723	3.32e-04	3.08e-03	34

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0501430	Esophagus	HGIN	Amyotrophic lateral sclerosis	140/1383	364/8465	2.13e-25	1.16e-23	9.19e-24	140
hsa0502230	Esophagus	HGIN	Pathways of neurodegeneration - multiple diseases	153/1383	476/8465	1.22e-18	4.41e-17	3.50e-17	153
hsa0501030	Esophagus	HGIN	Alzheimer disease	130/1383	384/8465	5.26e-18	1.71e-16	1.36e-16	130
hsa0493230	Esophagus	HGIN	Non-alcoholic fatty liver disease	66/1383	155/8465	5.21e-15	1.21e-13	9.64e-14	66
hsa0516930	Esophagus	HGIN	Epstein-Barr virus infection	55/1383	202/8465	5.13e-05	6.19e-04	4.92e-04	55
hsa0516730	Esophagus	HGIN	Kaposi sarcoma-associated herpesvirus infection	51/1383	194/8465	2.46e-04	2.69e-03	2.14e-03	51
hsa0421020	Esophagus	HGIN	Apoptosis	36/1383	136/8465	1.67e-03	1.52e-02	1.20e-02	36
hsa0517029	Esophagus	HGIN	Human immunodeficiency virus 1 infection	51/1383	212/8465	2.16e-03	1.90e-02	1.51e-02	51
hsa0541739	Esophagus	HGIN	Lipid and atherosclerosis	51/1383	215/8465	2.95e-03	2.41e-02	1.91e-02	51
hsa0516420	Esophagus	HGIN	Influenza A	42/1383	171/8465	3.41e-03	2.54e-02	2.02e-02	42
hsa0411510	Esophagus	HGIN	p53 signaling pathway	21/1383	74/8465	6.25e-03	4.25e-02	3.37e-02	21
hsa0516330	Esophagus	HGIN	Human cytomegalovirus infection	51/1383	225/8465	7.67e-03	4.63e-02	3.68e-02	51
hsa05014113	Esophagus	HGIN	Amyotrophic lateral sclerosis	140/1383	364/8465	2.13e-25	1.16e-23	9.19e-24	140
hsa05022113	Esophagus	HGIN	Pathways of neurodegeneration - multiple diseases	153/1383	476/8465	1.22e-18	4.41e-17	3.50e-17	153
hsa05010113	Esophagus	HGIN	Alzheimer disease	130/1383	384/8465	5.26e-18	1.71e-16	1.36e-16	130
hsa04932113	Esophagus	HGIN	Non-alcoholic fatty liver disease	66/1383	155/8465	5.21e-15	1.21e-13	9.64e-14	66
hsa05169114	Esophagus	HGIN	Epstein-Barr virus infection	55/1383	202/8465	5.13e-05	6.19e-04	4.92e-04	55
hsa05167114	Esophagus	HGIN	Kaposi sarcoma-associated herpesvirus infection	51/1383	194/8465	2.46e-04	2.69e-03	2.14e-03	51
hsa04210110	Esophagus	HGIN	Apoptosis	36/1383	136/8465	1.67e-03	1.52e-02	1.20e-02	36
hsa05170112	Esophagus	HGIN	Human immunodeficiency virus 1 infection	51/1383	212/8465	2.16e-03	1.90e-02	1.51e-02	51

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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

BID

SNV

Missense_Mutation

c.710N>A

p.Arg237Lys

p.R237K

P55957

protein_coding

deleterious(0.01)

benign(0.368)

TCGA-A2-A0CX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

BID

SNV

Missense_Mutation

c.641N>A

p.Arg214His

p.R214H

P55957

protein_coding

tolerated(0.26)

benign(0.141)

TCGA-AO-A124-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

BID

SNV

Missense_Mutation

c.178N>A

p.Glu60Lys

p.E60K

P55957

protein_coding

deleterious(0)

probably_damaging(0.931)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

BID

insertion

Frame_Shift_Ins

novel

c.385_386insGAATCGGATTAAGGACATCA

p.Ile129ArgfsTer31

p.I129Rfs*31

P55957

protein_coding

TCGA-AR-A1AQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

BID

deletion

In_Frame_Del

rs759487323

c.608_619delAGAAGGTGGCCA

p.Lys203_Ala206del

p.K203_A206del

P55957

protein_coding

TCGA-B6-A0X1-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

BID

SNV

Missense_Mutation

c.146N>A

p.Cys49Tyr

p.C49Y

P55957

protein_coding

deleterious(0.03)

benign(0.001)

TCGA-AA-3492-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

BID

SNV

Missense_Mutation

rs747016844

c.265G>A

p.Glu89Lys

p.E89K

P55957

protein_coding

tolerated(0.09)

benign(0.134)

TCGA-EI-6917-01

Colorectum

rectum adenocarcinoma

Male

<65

III/IV

Chemotherapy

5fluorouracil+oxaciplatina+l-folinian

BID

SNV

Missense_Mutation

rs547322681

c.626C>T

p.Thr209Met

p.T209M

P55957

protein_coding

tolerated(0.35)

benign(0.23)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

BID

SNV

Missense_Mutation

novel

c.350G>T

p.Arg117Ile

p.R117I

P55957

protein_coding

tolerated(0.12)

benign(0.26)

TCGA-AP-A059-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

BID

SNV

Missense_Mutation

rs575351241

c.446N>T

p.Pro149Leu

p.P149L

P55957

protein_coding

tolerated(0.17)

benign(0.068)

TCGA-AP-A1DK-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

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