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: RNF149

Gene summary for RNF149

Gene summary.

Gene information	Species	Human
	Gene symbol	RNF149
	Gene ID	284996
	Gene name	ring finger protein 149
	Gene Alias	DNAPTP2
	Cytomap	2q11.2
	Gene Type	protein-coding
	GO ID	GO:0000165
	UniProtAcc	Q8NC42

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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
284996	RNF149	HTA11_347_2000001011	Human	Colorectum	AD	1.61e-06	4.46e-01	-0.1954
284996	RNF149	HTA11_411_2000001011	Human	Colorectum	SER	7.39e-04	8.45e-01	-0.2602
284996	RNF149	HTA11_1391_2000001011	Human	Colorectum	AD	1.89e-03	4.57e-01	-0.059
284996	RNF149	HTA11_99999970781_79442	Human	Colorectum	MSS	1.45e-04	4.55e-01	0.294
284996	RNF149	HTA11_99999971662_82457	Human	Colorectum	MSS	1.56e-03	4.92e-01	0.3859
284996	RNF149	A015-C-203	Human	Colorectum	FAP	8.98e-21	-3.48e-01	-0.1294
284996	RNF149	A015-C-204	Human	Colorectum	FAP	2.66e-04	-3.00e-01	-0.0228
284996	RNF149	A002-C-201	Human	Colorectum	FAP	1.83e-08	-2.23e-01	0.0324
284996	RNF149	A001-C-108	Human	Colorectum	FAP	8.02e-13	-2.52e-01	-0.0272
284996	RNF149	A002-C-205	Human	Colorectum	FAP	1.04e-13	-3.06e-01	-0.1236
284996	RNF149	A001-C-104	Human	Colorectum	FAP	3.02e-02	-1.62e-01	0.0184
284996	RNF149	A015-C-006	Human	Colorectum	FAP	2.00e-11	-3.19e-02	-0.0994
284996	RNF149	A015-C-106	Human	Colorectum	FAP	2.51e-06	-2.09e-01	-0.0511
284996	RNF149	A002-C-114	Human	Colorectum	FAP	2.16e-10	-2.75e-01	-0.1561
284996	RNF149	A015-C-104	Human	Colorectum	FAP	8.31e-25	-1.47e-01	-0.1899
284996	RNF149	A001-C-014	Human	Colorectum	FAP	2.23e-10	-1.74e-01	0.0135
284996	RNF149	A002-C-016	Human	Colorectum	FAP	1.67e-15	-2.98e-01	0.0521
284996	RNF149	A015-C-002	Human	Colorectum	FAP	5.40e-07	-2.87e-01	-0.0763
284996	RNF149	A001-C-203	Human	Colorectum	FAP	5.87e-09	-2.24e-01	-0.0481
284996	RNF149	A002-C-116	Human	Colorectum	FAP	3.84e-26	-2.71e-01	-0.0452

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Colorectum (GSE201348)		FAP: Familial adenomatous polyposis
		CRC: Colorectal cancer
Colorectum (HTA11)		AD: Adenomas
		SER: Sessile serrated lesions
		MSI-H: Microsatellite-high colorectal cancer
		MSS: Microsatellite stable colorectal 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
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
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:0031647	Colorectum	AD	regulation of protein stability	108/3918	298/18723	6.33e-10	5.08e-08	108
GO:0009410	Colorectum	AD	response to xenobiotic stimulus	128/3918	462/18723	2.69e-04	3.31e-03	128
GO:0043409	Colorectum	AD	negative regulation of MAPK cascade	57/3918	180/18723	4.61e-04	5.14e-03	57
GO:00316471	Colorectum	SER	regulation of protein stability	86/2897	298/18723	2.56e-09	2.42e-07	86
GO:00434091	Colorectum	SER	negative regulation of MAPK cascade	45/2897	180/18723	5.81e-04	7.98e-03	45
GO:00316472	Colorectum	MSS	regulation of protein stability	103/3467	298/18723	2.52e-11	3.49e-09	103
GO:00434092	Colorectum	MSS	negative regulation of MAPK cascade	50/3467	180/18723	1.45e-03	1.35e-02	50
GO:00094101	Colorectum	MSS	response to xenobiotic stimulus	110/3467	462/18723	2.36e-03	1.92e-02	110
GO:00316474	Colorectum	FAP	regulation of protein stability	70/2622	298/18723	6.60e-06	2.04e-04	70
GO:00434094	Colorectum	FAP	negative regulation of MAPK cascade	42/2622	180/18723	4.97e-04	5.72e-03	42
GO:00094102	Colorectum	FAP	response to xenobiotic stimulus	87/2622	462/18723	2.15e-03	1.77e-02	87
GO:00316475	Colorectum	CRC	regulation of protein stability	58/2078	298/18723	1.38e-05	4.37e-04	58
GO:00434095	Colorectum	CRC	negative regulation of MAPK cascade	37/2078	180/18723	1.51e-04	2.74e-03	37
GO:00094103	Colorectum	CRC	response to xenobiotic stimulus	69/2078	462/18723	6.34e-03	4.61e-02	69
GO:003164727	Esophagus	HGIN	regulation of protein stability	96/2587	298/18723	2.21e-16	5.76e-14	96
GO:004340919	Esophagus	HGIN	negative regulation of MAPK cascade	38/2587	180/18723	4.58e-03	3.96e-02	38
GO:0031647111	Esophagus	ESCC	regulation of protein stability	223/8552	298/18723	5.76e-25	1.52e-22	223
GO:000941020	Esophagus	ESCC	response to xenobiotic stimulus	253/8552	462/18723	4.55e-05	3.58e-04	253
GO:0043409110	Esophagus	ESCC	negative regulation of MAPK cascade	105/8552	180/18723	4.13e-04	2.35e-03	105
GO:00094107	Liver	NAFLD	response to xenobiotic stimulus	88/1882	462/18723	2.53e-09	4.11e-07	88

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Enriched KEGG pathways.

Pathway ID

Tissue

Disease Stage

Description

Gene Ratio

Bg Ratio

pvalue

p.adjust

qvalue

Count

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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

RNF149

SNV

Missense_Mutation

c.508N>C

p.Glu170Gln

p.E170Q

Q8NC42

protein_coding

deleterious(0)

probably_damaging(0.966)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

RNF149

SNV

Missense_Mutation

c.710N>G

p.Gln237Arg

p.Q237R

Q8NC42

protein_coding

deleterious(0.02)

probably_damaging(0.994)

TCGA-D8-A1XK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine+cyclophosphamide

RNF149

SNV

Missense_Mutation

novel

c.418G>A

p.Glu140Lys

p.E140K

Q8NC42

protein_coding

tolerated(0.7)

benign(0.018)

TCGA-VS-A9UP-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

RNF149

SNV

Missense_Mutation

novel

c.311G>A

p.Arg104Gln

p.R104Q

Q8NC42

protein_coding

tolerated(0.74)

benign(0.003)

TCGA-VS-A9UP-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

RNF149

SNV

Missense_Mutation

novel

c.28N>A

p.Val10Ile

p.V10I

Q8NC42

protein_coding

tolerated_low_confidence(0.28)

benign(0)

TCGA-5M-AAT6-01

Colorectum

colon adenocarcinoma

Female

<65

III/IV

Unknown

RNF149

SNV

Missense_Mutation

novel

c.713N>A

p.Ser238Asn

p.S238N

Q8NC42

protein_coding

tolerated(0.18)

benign(0.006)

TCGA-F5-6814-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

RNF149

SNV

Missense_Mutation

rs772808658

c.775G>A

p.Glu259Lys

p.E259K

Q8NC42

protein_coding

deleterious(0)

benign(0.411)

TCGA-AX-A2HC-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

RNF149

SNV

Missense_Mutation

c.878N>T

p.Arg293Ile

p.R293I

Q8NC42

protein_coding

deleterious(0)

probably_damaging(0.977)

TCGA-B5-A0JY-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

RNF149

SNV

Missense_Mutation

c.566C>A

p.Thr189Asn

p.T189N

Q8NC42

protein_coding

deleterious(0.02)

possibly_damaging(0.879)

TCGA-D1-A163-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

taxol

RNF149

SNV

Missense_Mutation

rs574716905

c.644N>T

p.Ser215Leu

p.S215L

Q8NC42

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-E6-A1M0-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

carboplatin

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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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