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: SCAF8

Gene summary for SCAF8

Gene summary.

Gene information	Species	Human
	Gene symbol	SCAF8
	Gene ID	22828
	Gene name	SR-related CTD associated factor 8
	Gene Alias	RBM16
	Cytomap	6q25.2
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	A0A0A0MT33

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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
22828	SCAF8	CCI_1	Human	Cervix	CC	4.46e-02	4.49e-01	0.528
22828	SCAF8	CCI_2	Human	Cervix	CC	8.61e-09	7.49e-01	0.5249
22828	SCAF8	CCI_3	Human	Cervix	CC	2.93e-11	8.40e-01	0.516
22828	SCAF8	HTA11_3410_2000001011	Human	Colorectum	AD	9.57e-06	-3.54e-01	0.0155
22828	SCAF8	HTA11_347_2000001011	Human	Colorectum	AD	2.48e-02	3.57e-01	-0.1954
22828	SCAF8	HTA11_7696_3000711011	Human	Colorectum	AD	4.17e-03	-3.78e-01	0.0674
22828	SCAF8	HTA11_99999970781_79442	Human	Colorectum	MSS	5.56e-03	4.12e-01	0.294
22828	SCAF8	HTA11_99999974143_84620	Human	Colorectum	MSS	3.99e-13	-5.46e-01	0.3005
22828	SCAF8	A002-C-010	Human	Colorectum	FAP	1.36e-03	-1.73e-01	0.242
22828	SCAF8	A015-C-203	Human	Colorectum	FAP	4.37e-28	-5.43e-01	-0.1294
22828	SCAF8	A015-C-204	Human	Colorectum	FAP	2.70e-07	-4.14e-01	-0.0228
22828	SCAF8	A014-C-040	Human	Colorectum	FAP	1.94e-08	-7.48e-01	-0.1184
22828	SCAF8	A002-C-201	Human	Colorectum	FAP	1.30e-15	-4.27e-01	0.0324
22828	SCAF8	A002-C-203	Human	Colorectum	FAP	3.46e-04	-2.53e-01	0.2786
22828	SCAF8	A001-C-119	Human	Colorectum	FAP	7.07e-12	-5.93e-01	-0.1557
22828	SCAF8	A001-C-108	Human	Colorectum	FAP	1.37e-16	-4.15e-01	-0.0272
22828	SCAF8	A002-C-205	Human	Colorectum	FAP	1.82e-28	-6.35e-01	-0.1236
22828	SCAF8	A001-C-104	Human	Colorectum	FAP	2.73e-05	-3.54e-01	0.0184
22828	SCAF8	A015-C-005	Human	Colorectum	FAP	1.10e-04	-3.22e-01	-0.0336
22828	SCAF8	A015-C-006	Human	Colorectum	FAP	1.64e-18	-5.65e-01	-0.0994

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
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
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
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
Prostate		BPH: Benign Prostatic Hyperplasia

∗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:002241110	Cervix	CC	cellular component disassembly	83/2311	443/18723	6.04e-05	8.68e-04	83
GO:00329847	Cervix	CC	protein-containing complex disassembly	41/2311	224/18723	6.13e-03	3.48e-02	41
GO:00063545	Cervix	CC	DNA-templated transcription, elongation	20/2311	91/18723	6.88e-03	3.74e-02	20
GO:0022411	Colorectum	AD	cellular component disassembly	147/3918	443/18723	8.53e-10	6.76e-08	147
GO:0032984	Colorectum	AD	protein-containing complex disassembly	81/3918	224/18723	9.41e-08	4.65e-06	81
GO:0043244	Colorectum	AD	regulation of protein-containing complex disassembly	41/3918	121/18723	6.22e-04	6.48e-03	41
GO:0032786	Colorectum	AD	positive regulation of DNA-templated transcription, elongation	13/3918	27/18723	1.47e-03	1.25e-02	13
GO:0043242	Colorectum	AD	negative regulation of protein-containing complex disassembly	29/3918	82/18723	1.76e-03	1.45e-02	29
GO:0006354	Colorectum	AD	DNA-templated transcription, elongation	31/3918	91/18723	2.46e-03	1.90e-02	31
GO:00224112	Colorectum	MSS	cellular component disassembly	130/3467	443/18723	1.44e-08	8.46e-07	130
GO:00329842	Colorectum	MSS	protein-containing complex disassembly	69/3467	224/18723	5.61e-06	1.50e-04	69
GO:00063541	Colorectum	MSS	DNA-templated transcription, elongation	29/3467	91/18723	1.52e-03	1.39e-02	29
GO:00327861	Colorectum	MSS	positive regulation of DNA-templated transcription, elongation	12/3467	27/18723	1.74e-03	1.55e-02	12
GO:00224114	Colorectum	FAP	cellular component disassembly	97/2622	443/18723	3.44e-06	1.23e-04	97
GO:00329844	Colorectum	FAP	protein-containing complex disassembly	54/2622	224/18723	3.37e-05	7.48e-04	54
GO:00327862	Colorectum	FAP	positive regulation of DNA-templated transcription, elongation	11/2622	27/18723	5.93e-04	6.58e-03	11
GO:00063542	Colorectum	FAP	DNA-templated transcription, elongation	24/2622	91/18723	1.32e-03	1.22e-02	24
GO:00432442	Colorectum	FAP	regulation of protein-containing complex disassembly	28/2622	121/18723	4.50e-03	3.06e-02	28
GO:00432421	Colorectum	FAP	negative regulation of protein-containing complex disassembly	20/2622	82/18723	8.23e-03	4.82e-02	20
GO:00329845	Colorectum	CRC	protein-containing complex disassembly	46/2078	224/18723	2.61e-05	7.18e-04	46

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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

SCAF8

SNV

Missense_Mutation

c.1592G>A

p.Arg531Lys

p.R531K

protein_coding

tolerated(0.06)

probably_damaging(0.913)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SCAF8

SNV

Missense_Mutation

rs754810889

c.3604N>T

p.Arg1202Trp

p.R1202W

protein_coding

deleterious_low_confidence(0.02)

probably_damaging(0.999)

TCGA-AC-A6IW-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SCAF8

SNV

Missense_Mutation

rs200535713

c.1448G>A

p.Arg483Gln

p.R483Q

protein_coding

tolerated_low_confidence(0.06)

benign(0.007)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SCAF8

SNV

Missense_Mutation

rs769802562

c.3815G>A

p.Arg1272Gln

p.R1272Q

protein_coding

tolerated_low_confidence(0.25)

probably_damaging(0.997)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SCAF8

SNV

Missense_Mutation

c.3932N>T

p.Asp1311Val

p.D1311V

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.969)

TCGA-AN-A0AM-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SCAF8

SNV

Missense_Mutation

c.2075C>G

p.Thr692Arg

p.T692R

protein_coding

tolerated(0.05)

probably_damaging(0.962)

TCGA-D8-A1JJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine

SCAF8

SNV

Missense_Mutation

c.1091N>T

p.Ser364Leu

p.S364L

protein_coding

deleterious(0)

benign(0.196)

TCGA-GM-A2DH-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxol

SCAF8

SNV

Missense_Mutation

novel

c.3047N>A

p.Arg1016Lys

p.R1016K

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.839)

TCGA-OL-A66K-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SCAF8

insertion

Nonsense_Mutation

novel

c.1690_1691insCCATGCCCGGCCAGTATTTTAGACTAATATTATTACTGGTCATCATTT

p.Lys564delinsThrMetProGlyGlnTyrPheArgLeuIleLeuLeuLeuValIleIleTer

p.K564delinsTMPGQYFRLILLLVII*

protein_coding

TCGA-B6-A0X1-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SCAF8

deletion

Frame_Shift_Del

novel

c.2832_2845delNNNNNNNNNNNNNN

p.Gly945AlafsTer7

p.G945Afs*7

protein_coding

TCGA-B6-A400-01

Breast

breast invasive carcinoma

Female

<65

III/IV

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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