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: JAK1

Gene summary for JAK1

Gene summary.

Gene information	Species	Human
	Gene symbol	JAK1
	Gene ID	3716
	Gene name	Janus kinase 1
	Gene Alias	AIIDE
	Cytomap	1p31.3
	Gene Type	protein-coding
	GO ID	GO:0001525
	UniProtAcc	P23458

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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
3716	JAK1	LZE2T	Human	Esophagus	ESCC	6.67e-04	2.70e-01	0.082
3716	JAK1	LZE4T	Human	Esophagus	ESCC	1.72e-19	5.92e-01	0.0811
3716	JAK1	LZE5T	Human	Esophagus	ESCC	1.35e-10	4.51e-01	0.0514
3716	JAK1	LZE7T	Human	Esophagus	ESCC	1.18e-05	2.17e-01	0.0667
3716	JAK1	LZE20T	Human	Esophagus	ESCC	9.62e-09	3.98e-01	0.0662
3716	JAK1	LZE22T	Human	Esophagus	ESCC	2.33e-07	3.86e-01	0.068
3716	JAK1	LZE24T	Human	Esophagus	ESCC	2.47e-26	6.24e-01	0.0596
3716	JAK1	LZE21T	Human	Esophagus	ESCC	1.05e-02	1.43e-01	0.0655
3716	JAK1	P1T-E	Human	Esophagus	ESCC	4.12e-11	1.15e+00	0.0875
3716	JAK1	P2T-E	Human	Esophagus	ESCC	9.67e-68	1.04e+00	0.1177
3716	JAK1	P4T-E	Human	Esophagus	ESCC	1.96e-29	6.34e-01	0.1323
3716	JAK1	P5T-E	Human	Esophagus	ESCC	3.59e-25	5.91e-01	0.1327
3716	JAK1	P8T-E	Human	Esophagus	ESCC	1.37e-27	6.24e-01	0.0889
3716	JAK1	P9T-E	Human	Esophagus	ESCC	4.02e-13	4.49e-01	0.1131
3716	JAK1	P10T-E	Human	Esophagus	ESCC	7.87e-37	5.95e-01	0.116
3716	JAK1	P11T-E	Human	Esophagus	ESCC	1.97e-22	7.30e-01	0.1426
3716	JAK1	P12T-E	Human	Esophagus	ESCC	3.09e-24	6.09e-01	0.1122
3716	JAK1	P15T-E	Human	Esophagus	ESCC	2.39e-38	7.84e-01	0.1149
3716	JAK1	P16T-E	Human	Esophagus	ESCC	9.55e-21	2.80e-01	0.1153
3716	JAK1	P17T-E	Human	Esophagus	ESCC	1.44e-16	7.74e-01	0.1278

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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
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:002240915	Prostate	BPH	positive regulation of cell-cell adhesion	67/3107	284/18723	1.41e-03	8.40e-03	67
GO:00341103	Prostate	BPH	regulation of homotypic cell-cell adhesion	13/3107	33/18723	1.50e-03	8.85e-03	13
GO:19024143	Prostate	BPH	protein localization to cell junction	27/3107	94/18723	2.25e-03	1.24e-02	27
GO:00341122	Prostate	BPH	positive regulation of homotypic cell-cell adhesion	7/3107	13/18723	2.33e-03	1.27e-02	7
GO:19013424	Prostate	BPH	regulation of vasculature development	78/3107	348/18723	2.76e-03	1.46e-02	78
GO:00457654	Prostate	BPH	regulation of angiogenesis	76/3107	342/18723	3.90e-03	1.95e-02	76
GO:00343416	Prostate	BPH	response to interferon-gamma	36/3107	141/18723	4.41e-03	2.16e-02	36
GO:004578519	Prostate	Tumor	positive regulation of cell adhesion	125/3246	437/18723	2.56e-09	1.08e-07	125
GO:003410918	Prostate	Tumor	homotypic cell-cell adhesion	33/3246	90/18723	9.06e-06	1.32e-04	33
GO:002240717	Prostate	Tumor	regulation of cell-cell adhesion	112/3246	448/18723	2.20e-05	2.80e-04	112
GO:015010515	Prostate	Tumor	protein localization to cell-cell junction	12/3246	21/18723	4.49e-05	5.04e-04	12
GO:002240916	Prostate	Tumor	positive regulation of cell-cell adhesion	70/3246	284/18723	1.06e-03	6.87e-03	70
GO:190241412	Prostate	Tumor	protein localization to cell junction	28/3246	94/18723	2.03e-03	1.16e-02	28
GO:003411011	Prostate	Tumor	regulation of homotypic cell-cell adhesion	13/3246	33/18723	2.26e-03	1.28e-02	13
GO:00341121	Prostate	Tumor	positive regulation of homotypic cell-cell adhesion	7/3246	13/18723	3.02e-03	1.61e-02	7
GO:003434113	Prostate	Tumor	response to interferon-gamma	37/3246	141/18723	5.07e-03	2.46e-02	37
GO:190134212	Prostate	Tumor	regulation of vasculature development	79/3246	348/18723	5.84e-03	2.71e-02	79
GO:004576512	Prostate	Tumor	regulation of angiogenesis	77/3246	342/18723	7.92e-03	3.52e-02	77
GO:00713464	Prostate	Tumor	cellular response to interferon-gamma	31/3246	118/18723	9.53e-03	4.09e-02	31
GO:00603334	Prostate	Tumor	interferon-gamma-mediated signaling pathway	10/3246	27/18723	1.17e-02	4.79e-02	10

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa05166211	Esophagus	ESCC	Human T-cell leukemia virus 1 infection	164/4205	222/8465	8.13e-14	2.09e-12	1.07e-12	164
hsa05169210	Esophagus	ESCC	Epstein-Barr virus infection	151/4205	202/8465	1.55e-13	3.45e-12	1.77e-12	151
hsa05167211	Esophagus	ESCC	Kaposi sarcoma-associated herpesvirus infection	136/4205	194/8465	4.28e-09	4.22e-08	2.16e-08	136
hsa0516425	Esophagus	ESCC	Influenza A	122/4205	171/8465	5.01e-09	4.79e-08	2.45e-08	122
hsa0521216	Esophagus	ESCC	Pancreatic cancer	62/4205	76/8465	7.37e-09	6.85e-08	3.51e-08	62
hsa0516510	Esophagus	ESCC	Human papillomavirus infection	215/4205	331/8465	7.86e-09	7.12e-08	3.65e-08	215
hsa05171211	Esophagus	ESCC	Coronavirus disease - COVID-19	156/4205	232/8465	3.18e-08	2.68e-07	1.37e-07	156
hsa0520325	Esophagus	ESCC	Viral carcinogenesis	137/4205	204/8465	2.47e-07	1.88e-06	9.62e-07	137
hsa05163210	Esophagus	ESCC	Human cytomegalovirus infection	148/4205	225/8465	5.73e-07	4.00e-06	2.05e-06	148
hsa051609	Esophagus	ESCC	Hepatitis C	107/4205	157/8465	1.75e-06	1.08e-05	5.55e-06	107
hsa051619	Esophagus	ESCC	Hepatitis B	108/4205	162/8465	7.68e-06	4.15e-05	2.12e-05	108
hsa0514525	Esophagus	ESCC	Toxoplasmosis	76/4205	112/8465	6.83e-05	2.90e-04	1.48e-04	76
hsa051629	Esophagus	ESCC	Measles	90/4205	139/8465	2.16e-04	7.87e-04	4.03e-04	90
hsa0152110	Esophagus	ESCC	EGFR tyrosine kinase inhibitor resistance	55/4205	79/8465	2.44e-04	8.78e-04	4.50e-04	55
hsa0462122	Esophagus	ESCC	NOD-like receptor signaling pathway	116/4205	186/8465	2.90e-04	1.03e-03	5.30e-04	116
hsa051527	Esophagus	ESCC	Tuberculosis	111/4205	180/8465	7.14e-04	2.32e-03	1.19e-03	111
hsa052356	Esophagus	ESCC	PD-L1 expression and PD-1 checkpoint pathway in cancer	58/4205	89/8465	2.19e-03	6.16e-03	3.16e-03	58
hsa046599	Esophagus	ESCC	Th17 cell differentiation	68/4205	108/8465	3.53e-03	9.30e-03	4.76e-03	68
hsa046585	Esophagus	ESCC	Th1 and Th2 cell differentiation	58/4205	92/8465	6.49e-03	1.60e-02	8.19e-03	58
hsa041517	Esophagus	ESCC	PI3K-Akt signaling pathway	197/4205	354/8465	1.24e-02	2.83e-02	1.45e-02	197

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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

JAK1

SNV

Missense_Mutation

novel

c.3299N>A

p.Thr1100Lys

p.T1100K

P23458

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-A7-A13E-01

Breast

breast invasive carcinoma

Female

<65

I/II

Targeted Molecular therapy

bevacizumab

JAK1

SNV

Missense_Mutation

c.3268N>C

p.Lys1090Gln

p.K1090Q

P23458

protein_coding

deleterious(0.03)

benign(0.115)

TCGA-A8-A08T-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

JAK1

SNV

Missense_Mutation

c.1798G>T

p.Gly600Trp

p.G600W

P23458

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-A8-A095-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

JAK1

SNV

Missense_Mutation

c.3392N>A

p.Cys1131Tyr

p.C1131Y

P23458

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

JAK1

SNV

Missense_Mutation

c.1406N>A

p.Cys469Tyr

p.C469Y

P23458

protein_coding

deleterious(0.01)

probably_damaging(0.996)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

JAK1

SNV

Missense_Mutation

c.566N>A

p.Cys189Tyr

p.C189Y

P23458

protein_coding

tolerated(0.09)

probably_damaging(0.996)

TCGA-E9-A1R7-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

fareston

JAK1

insertion

In_Frame_Ins

novel

c.1997_1998insTCCTTCATT

p.Val666_Glu667insProSerLeu

p.V666_E667insPSL

P23458

protein_coding

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

JAK1

insertion

Nonsense_Mutation

novel

c.1995_1996insTTTGGGCACACTGCTTGAAGTA

p.Val666PhefsTer6

p.V666Ffs*6

P23458

protein_coding

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

JAK1

insertion

Nonsense_Mutation

novel

c.2052_2053insAGTATTATTTATCTGAGATTTTAA

p.Asp684_Val685insSerIleIleTyrLeuArgPheTer

p.D684_V685insSIIYLRF*

P23458

protein_coding

TCGA-AN-A04A-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

JAK1

insertion

Frame_Shift_Ins

novel

c.1035_1036insA

p.Leu346ThrfsTer4

p.L346Tfs*4

P23458

protein_coding

TCGA-D8-A145-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

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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
3716	JAK1	CLINICALLY ACTIONABLE, DRUG RESISTANCE, DRUGGABLE GENOME, KINASE, TYROSINE KINASE, ENZYME		PEMBROLIZUMAB	PEMBROLIZUMAB	27903500,27433843
3716	JAK1	CLINICALLY ACTIONABLE, DRUG RESISTANCE, DRUGGABLE GENOME, KINASE, TYROSINE KINASE, ENZYME		PMID27774824-Compound-Figure9Example2up
3716	JAK1	CLINICALLY ACTIONABLE, DRUG RESISTANCE, DRUGGABLE GENOME, KINASE, TYROSINE KINASE, ENZYME		Aminotriazolopyridine derivative 1
3716	JAK1	CLINICALLY ACTIONABLE, DRUG RESISTANCE, DRUGGABLE GENOME, KINASE, TYROSINE KINASE, ENZYME		Pyrazolo[4,3-c]pyridine derivative 2
3716	JAK1	CLINICALLY ACTIONABLE, DRUG RESISTANCE, DRUGGABLE GENOME, KINASE, TYROSINE KINASE, ENZYME	inhibitor	381118867
3716	JAK1	CLINICALLY ACTIONABLE, DRUG RESISTANCE, DRUGGABLE GENOME, KINASE, TYROSINE KINASE, ENZYME		Tricyclic heterocycle derivative 1
3716	JAK1	CLINICALLY ACTIONABLE, DRUG RESISTANCE, DRUGGABLE GENOME, KINASE, TYROSINE KINASE, ENZYME	inhibitor	348353655	OCLACITINIB
3716	JAK1	CLINICALLY ACTIONABLE, DRUG RESISTANCE, DRUGGABLE GENOME, KINASE, TYROSINE KINASE, ENZYME		Five-and-six-membered heterocyclic compound 1
3716	JAK1	CLINICALLY ACTIONABLE, DRUG RESISTANCE, DRUGGABLE GENOME, KINASE, TYROSINE KINASE, ENZYME		Bipyrazole derivative 1
3716	JAK1	CLINICALLY ACTIONABLE, DRUG RESISTANCE, DRUGGABLE GENOME, KINASE, TYROSINE KINASE, ENZYME	inhibitor	385612219	BREPOCITINIB

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