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: IFI16

Gene summary for IFI16

Gene summary.

Gene information	Species	Human
	Gene symbol	IFI16
	Gene ID	3428
	Gene name	interferon gamma inducible protein 16
	Gene Alias	IFNGIP1
	Cytomap	1q23.1
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	Q16666

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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
3428	IFI16	GSM4909285	Human	Breast	IDC	3.85e-08	-1.98e-01	0.21
3428	IFI16	GSM4909286	Human	Breast	IDC	3.85e-08	-2.04e-01	0.1081
3428	IFI16	GSM4909287	Human	Breast	IDC	2.02e-16	6.58e-01	0.2057
3428	IFI16	GSM4909296	Human	Breast	IDC	1.78e-08	-2.05e-01	0.1524
3428	IFI16	GSM4909297	Human	Breast	IDC	3.04e-04	-1.50e-01	0.1517
3428	IFI16	GSM4909301	Human	Breast	IDC	1.53e-03	-1.79e-01	0.1577
3428	IFI16	GSM4909302	Human	Breast	IDC	3.01e-02	-1.71e-01	0.1545
3428	IFI16	GSM4909311	Human	Breast	IDC	3.85e-08	-2.05e-01	0.1534
3428	IFI16	GSM4909312	Human	Breast	IDC	1.78e-08	-2.05e-01	0.1552
3428	IFI16	GSM4909319	Human	Breast	IDC	3.44e-06	-1.97e-01	0.1563
3428	IFI16	GSM4909321	Human	Breast	IDC	3.85e-08	-2.05e-01	0.1559
3428	IFI16	NCCBC3	Human	Breast	DCIS	1.15e-08	3.95e-01	0.1198
3428	IFI16	P2	Human	Breast	IDC	7.44e-09	6.36e-01	0.21
3428	IFI16	DCIS2	Human	Breast	DCIS	2.01e-67	4.97e-01	0.0085
3428	IFI16	CA_HPV_1	Human	Cervix	CC	7.26e-10	2.05e-01	0.0264
3428	IFI16	CA_HPV_2	Human	Cervix	CC	3.04e-06	3.78e-01	0.0391
3428	IFI16	CCI_1	Human	Cervix	CC	4.03e-09	1.13e+00	0.528
3428	IFI16	CCI_2	Human	Cervix	CC	3.01e-11	1.40e+00	0.5249
3428	IFI16	CCI_3	Human	Cervix	CC	2.91e-04	5.67e-01	0.516
3428	IFI16	Tumor	Human	Cervix	CC	1.44e-02	2.57e-01	0.1241

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
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
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
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:00109508	Lung	IAC	positive regulation of endopeptidase activity	35/2061	179/18723	5.15e-04	7.37e-03	35
GO:00096156	Lung	IAC	response to virus	61/2061	367/18723	6.75e-04	9.12e-03	61
GO:00511007	Lung	IAC	negative regulation of binding	32/2061	162/18723	7.30e-04	9.60e-03	32
GO:00458618	Lung	IAC	negative regulation of proteolysis	58/2061	351/18723	1.04e-03	1.24e-02	58
GO:0043392	Lung	IAC	negative regulation of DNA binding	14/2061	52/18723	1.14e-03	1.33e-02	14
GO:00302247	Lung	IAC	monocyte differentiation	11/2061	36/18723	1.23e-03	1.42e-02	11
GO:20010567	Lung	IAC	positive regulation of cysteine-type endopeptidase activity	29/2061	148/18723	1.44e-03	1.55e-02	29
GO:20001178	Lung	IAC	negative regulation of cysteine-type endopeptidase activity	19/2061	86/18723	2.22e-03	2.18e-02	19
GO:19031311	Lung	IAC	mononuclear cell differentiation	66/2061	426/18723	2.63e-03	2.44e-02	66
GO:00092676	Lung	IAC	cellular response to starvation	29/2061	156/18723	3.26e-03	2.80e-02	29
GO:00321033	Lung	IAC	positive regulation of response to external stimulus	65/2061	427/18723	4.28e-03	3.41e-02	65
GO:00425946	Lung	IAC	response to starvation	34/2061	197/18723	5.29e-03	4.00e-02	34
GO:00109518	Lung	IAC	negative regulation of endopeptidase activity	41/2061	252/18723	6.84e-03	4.75e-02	41
GO:00025736	Lung	IAC	myeloid leukocyte differentiation	35/2061	208/18723	7.05e-03	4.83e-02	35
GO:001603213	Lung	AIS	viral process	85/1849	415/18723	4.74e-11	1.95e-08	85
GO:007233113	Lung	AIS	signal transduction by p53 class mediator	44/1849	163/18723	3.66e-10	8.87e-08	44
GO:001905813	Lung	AIS	viral life cycle	68/1849	317/18723	5.39e-10	1.16e-07	68
GO:009719313	Lung	AIS	intrinsic apoptotic signaling pathway	63/1849	288/18723	1.02e-09	2.12e-07	63
GO:004586213	Lung	AIS	positive regulation of proteolysis	73/1849	372/18723	7.68e-09	1.21e-06	73
GO:007233213	Lung	AIS	intrinsic apoptotic signaling pathway by p53 class mediator	22/1849	76/18723	2.53e-06	1.42e-04	22

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa046213	Cervix	CC	NOD-like receptor signaling pathway	41/1267	186/8465	5.90e-03	1.95e-02	1.15e-02	41
hsa0462112	Cervix	CC	NOD-like receptor signaling pathway	41/1267	186/8465	5.90e-03	1.95e-02	1.15e-02	41
hsa046219	Esophagus	HGIN	NOD-like receptor signaling pathway	45/1383	186/8465	3.40e-03	2.54e-02	2.02e-02	45
hsa0462114	Esophagus	HGIN	NOD-like receptor signaling pathway	45/1383	186/8465	3.40e-03	2.54e-02	2.02e-02	45
hsa0462122	Esophagus	ESCC	NOD-like receptor signaling pathway	116/4205	186/8465	2.90e-04	1.03e-03	5.30e-04	116
hsa0462132	Esophagus	ESCC	NOD-like receptor signaling pathway	116/4205	186/8465	2.90e-04	1.03e-03	5.30e-04	116
hsa046212	Lung	IAC	NOD-like receptor signaling pathway	38/1053	186/8465	1.23e-03	8.24e-03	5.47e-03	38
hsa0462111	Lung	IAC	NOD-like receptor signaling pathway	38/1053	186/8465	1.23e-03	8.24e-03	5.47e-03	38
hsa046218	Oral cavity	OSCC	NOD-like receptor signaling pathway	108/3704	186/8465	5.13e-05	2.07e-04	1.05e-04	108
hsa0462113	Oral cavity	OSCC	NOD-like receptor signaling pathway	108/3704	186/8465	5.13e-05	2.07e-04	1.05e-04	108
hsa0462121	Oral cavity	LP	NOD-like receptor signaling pathway	73/2418	186/8465	9.80e-04	4.53e-03	2.92e-03	73
hsa0462131	Oral cavity	LP	NOD-like receptor signaling pathway	73/2418	186/8465	9.80e-04	4.53e-03	2.92e-03	73
hsa046214	Oral cavity	EOLP	NOD-like receptor signaling pathway	48/1218	186/8465	2.51e-05	1.31e-04	7.70e-05	48
hsa046215	Oral cavity	EOLP	NOD-like receptor signaling pathway	48/1218	186/8465	2.51e-05	1.31e-04	7.70e-05	48
hsa046216	Oral cavity	NEOLP	NOD-like receptor signaling pathway	39/1112	186/8465	1.79e-03	7.91e-03	4.98e-03	39
hsa046217	Oral cavity	NEOLP	NOD-like receptor signaling pathway	39/1112	186/8465	1.79e-03	7.91e-03	4.98e-03	39

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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

IFI16

SNV

Missense_Mutation

c.1297N>A

p.Pro433Thr

p.P433T

Q16666

protein_coding

deleterious(0.02)

possibly_damaging(0.88)

TCGA-A2-A0CT-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cytoxan

IFI16

SNV

Missense_Mutation

c.649G>A

p.Glu217Lys

p.E217K

Q16666

protein_coding

tolerated(0.75)

possibly_damaging(0.469)

TCGA-A2-A0CX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

IFI16

SNV

Missense_Mutation

c.5N>A

p.Gly2Glu

p.G2E

Q16666

protein_coding

tolerated(1)

benign(0)

TCGA-BH-A0DS-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

cyclophosphamide

IFI16

SNV

Missense_Mutation

novel

c.1190A>G

p.Asn397Ser

p.N397S

Q16666

protein_coding

tolerated(0.52)

benign(0.192)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

IFI16

SNV

Missense_Mutation

c.1673A>T

p.Lys558Met

p.K558M

Q16666

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-E2-A10C-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

IFI16

SNV

Missense_Mutation

c.291G>C

p.Lys97Asn

p.K97N

Q16666

protein_coding

tolerated(0.08)

benign(0.019)

TCGA-E2-A1LB-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

IFI16

SNV

Missense_Mutation

c.2082N>C

p.Leu694Phe

p.L694F

Q16666

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-BI-A0VR-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unknown

IFI16

SNV

Missense_Mutation

c.717N>A

p.Phe239Leu

p.F239L

Q16666

protein_coding

deleterious(0.04)

benign(0.013)

TCGA-EA-A556-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

IFI16

SNV

Missense_Mutation

c.2082N>C

p.Leu694Phe

p.L694F

Q16666

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-HM-A4S6-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Chemotherapy

cisplatin

IFI16

SNV

Missense_Mutation

c.1267N>A

p.Glu423Lys

p.E423K

Q16666

protein_coding

tolerated(0.5)

benign(0.443)

TCGA-IR-A3LH-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

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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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