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: ASCC3

Gene summary for ASCC3

Gene summary.

Gene information	Species	Human
	Gene symbol	ASCC3
	Gene ID	10973
	Gene name	activating signal cointegrator 1 complex subunit 3
	Gene Alias	ASC1p200
	Cytomap	6q16.3
	Gene Type	protein-coding
	GO ID	GO:0006139
	UniProtAcc	B4DR60

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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
10973	ASCC3	N_HPV_1	Human	Cervix	N_HPV	2.21e-02	-1.29e-01	0.0079
10973	ASCC3	CCI_2	Human	Cervix	CC	5.37e-04	7.36e-01	0.5249
10973	ASCC3	CCI_3	Human	Cervix	CC	9.55e-14	1.18e+00	0.516
10973	ASCC3	HTA11_3410_2000001011	Human	Colorectum	AD	4.23e-20	-7.10e-01	0.0155
10973	ASCC3	HTA11_2487_2000001011	Human	Colorectum	SER	4.72e-04	-5.25e-01	-0.1808
10973	ASCC3	HTA11_3361_2000001011	Human	Colorectum	AD	4.42e-08	-6.75e-01	-0.1207
10973	ASCC3	HTA11_83_2000001011	Human	Colorectum	SER	1.80e-04	-6.20e-01	-0.1526
10973	ASCC3	HTA11_696_2000001011	Human	Colorectum	AD	8.82e-18	-5.54e-01	-0.1464
10973	ASCC3	HTA11_866_2000001011	Human	Colorectum	AD	1.06e-09	-4.18e-01	-0.1001
10973	ASCC3	HTA11_5212_2000001011	Human	Colorectum	AD	1.05e-03	-7.27e-01	-0.2061
10973	ASCC3	HTA11_7862_2000001011	Human	Colorectum	AD	1.85e-05	-6.90e-01	-0.0179
10973	ASCC3	HTA11_866_3004761011	Human	Colorectum	AD	4.44e-14	-5.72e-01	0.096
10973	ASCC3	HTA11_8622_2000001021	Human	Colorectum	SER	5.26e-05	-6.75e-01	0.0528
10973	ASCC3	HTA11_10711_2000001011	Human	Colorectum	AD	1.13e-04	-5.38e-01	0.0338
10973	ASCC3	HTA11_7696_3000711011	Human	Colorectum	AD	1.84e-14	-4.98e-01	0.0674
10973	ASCC3	HTA11_99999970781_79442	Human	Colorectum	MSS	2.18e-17	-5.57e-01	0.294
10973	ASCC3	HTA11_99999971662_82457	Human	Colorectum	MSS	4.01e-15	-4.79e-01	0.3859
10973	ASCC3	HTA11_99999973899_84307	Human	Colorectum	MSS	1.83e-06	-6.60e-01	0.2585
10973	ASCC3	HTA11_99999974143_84620	Human	Colorectum	MSS	6.67e-10	-4.57e-01	0.3005
10973	ASCC3	A001-C-207	Human	Colorectum	FAP	1.82e-03	-2.66e-01	0.1278

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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
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:001049810	Cervix	CC	proteasomal protein catabolic process	111/2311	490/18723	8.98e-11	1.58e-08	111
GO:004316110	Cervix	CC	proteasome-mediated ubiquitin-dependent protein catabolic process	91/2311	412/18723	1.65e-08	1.25e-06	91
GO:000641710	Cervix	CC	regulation of translation	89/2311	468/18723	1.86e-05	3.46e-04	89
GO:00323923	Cervix	CC	DNA geometric change	21/2311	90/18723	2.71e-03	1.85e-02	21
GO:001049815	Cervix	N_HPV	proteasomal protein catabolic process	27/534	490/18723	9.06e-04	1.08e-02	27
GO:000641725	Cervix	N_HPV	regulation of translation	26/534	468/18723	9.95e-04	1.18e-02	26
GO:004316115	Cervix	N_HPV	proteasome-mediated ubiquitin-dependent protein catabolic process	21/534	412/18723	7.76e-03	4.97e-02	21
GO:0010498	Colorectum	AD	proteasomal protein catabolic process	174/3918	490/18723	3.18e-14	7.66e-12	174
GO:0043161	Colorectum	AD	proteasome-mediated ubiquitin-dependent protein catabolic process	141/3918	412/18723	1.77e-10	1.68e-08	141
GO:0006417	Colorectum	AD	regulation of translation	141/3918	468/18723	1.32e-06	4.22e-05	141
GO:0032392	Colorectum	AD	DNA geometric change	31/3918	90/18723	2.02e-03	1.63e-02	31
GO:0006414	Colorectum	AD	translational elongation	21/3918	55/18723	2.53e-03	1.93e-02	21
GO:00104981	Colorectum	SER	proteasomal protein catabolic process	132/2897	490/18723	3.08e-11	5.55e-09	132
GO:00431611	Colorectum	SER	proteasome-mediated ubiquitin-dependent protein catabolic process	105/2897	412/18723	7.48e-08	4.70e-06	105
GO:00064171	Colorectum	SER	regulation of translation	100/2897	468/18723	3.76e-04	5.74e-03	100
GO:00064141	Colorectum	SER	translational elongation	17/2897	55/18723	3.00e-03	2.65e-02	17
GO:00104982	Colorectum	MSS	proteasomal protein catabolic process	157/3467	490/18723	2.39e-13	5.25e-11	157
GO:00431612	Colorectum	MSS	proteasome-mediated ubiquitin-dependent protein catabolic process	127/3467	412/18723	7.70e-10	6.32e-08	127
GO:00064172	Colorectum	MSS	regulation of translation	134/3467	468/18723	4.43e-08	2.38e-06	134
GO:00323921	Colorectum	MSS	DNA geometric change	29/3467	90/18723	1.26e-03	1.20e-02	29

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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

ASCC3

SNV

Missense_Mutation

novel

c.4738G>A

p.Ala1580Thr

p.A1580T

Q8N3C0

protein_coding

deleterious(0.01)

possibly_damaging(0.885)

TCGA-AC-A8OQ-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ASCC3

SNV

Missense_Mutation

c.407G>A

p.Arg136Gln

p.R136Q

Q8N3C0

protein_coding

tolerated(0.23)

benign(0.357)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ASCC3

SNV

Missense_Mutation

c.5005N>C

p.Asp1669His

p.D1669H

Q8N3C0

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AN-A0XW-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

ASCC3

SNV

Missense_Mutation

rs757716813

c.4696N>T

p.Arg1566Cys

p.R1566C

Q8N3C0

protein_coding

deleterious(0)

probably_damaging(0.98)

TCGA-AO-A03O-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

doxorubicin

ASCC3

SNV

Missense_Mutation

novel

c.6580N>A

p.Asp2194Asn

p.D2194N

Q8N3C0

protein_coding

deleterious_low_confidence(0.01)

benign(0.022)

TCGA-BH-A0B6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ASCC3

SNV

Missense_Mutation

novel

c.5851N>G

p.Ile1951Val

p.I1951V

Q8N3C0

protein_coding

tolerated(0.48)

benign(0.003)

TCGA-C8-A26Y-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ASCC3

SNV

Missense_Mutation

novel

c.3745N>C

p.Glu1249Gln

p.E1249Q

Q8N3C0

protein_coding

tolerated(0.13)

possibly_damaging(0.566)

TCGA-D8-A1XK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine+cyclophosphamide

ASCC3

SNV

Missense_Mutation

novel

c.5557G>A

p.Glu1853Lys

p.E1853K

Q8N3C0

protein_coding

tolerated(0.49)

benign(0.003)

TCGA-E2-A2P6-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

ASCC3

SNV

Missense_Mutation

c.2686N>C

p.Asp896His

p.D896H

Q8N3C0

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-GM-A2DH-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxol

ASCC3

SNV

Missense_Mutation

novel

c.3011N>T

p.Ala1004Val

p.A1004V

Q8N3C0

protein_coding

tolerated(0.09)

benign(0.281)

TCGA-LD-A66U-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

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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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