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: RYBP

Gene summary for RYBP

Gene summary.

Gene information	Species	Human
	Gene symbol	RYBP
	Gene ID	23429
	Gene name	RING1 and YY1 binding protein
	Gene Alias	AAP1
	Cytomap	3p13
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	Q8N488

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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
23429	RYBP	HTA11_3410_2000001011	Human	Colorectum	AD	4.85e-12	-4.61e-01	0.0155
23429	RYBP	HTA11_3361_2000001011	Human	Colorectum	AD	9.71e-05	-4.91e-01	-0.1207
23429	RYBP	HTA11_866_3004761011	Human	Colorectum	AD	1.54e-07	-4.30e-01	0.096
23429	RYBP	HTA11_7696_3000711011	Human	Colorectum	AD	6.69e-06	-3.43e-01	0.0674
23429	RYBP	HTA11_99999974143_84620	Human	Colorectum	MSS	7.74e-07	-4.11e-01	0.3005
23429	RYBP	A001-C-207	Human	Colorectum	FAP	6.57e-03	-2.65e-01	0.1278
23429	RYBP	A015-C-203	Human	Colorectum	FAP	2.75e-19	-3.97e-01	-0.1294
23429	RYBP	A015-C-204	Human	Colorectum	FAP	9.88e-06	-2.69e-01	-0.0228
23429	RYBP	A014-C-040	Human	Colorectum	FAP	6.75e-05	-4.78e-01	-0.1184
23429	RYBP	A002-C-201	Human	Colorectum	FAP	1.03e-11	-3.50e-01	0.0324
23429	RYBP	A001-C-119	Human	Colorectum	FAP	1.36e-13	-5.53e-01	-0.1557
23429	RYBP	A001-C-108	Human	Colorectum	FAP	3.32e-13	-4.76e-01	-0.0272
23429	RYBP	A002-C-205	Human	Colorectum	FAP	2.69e-23	-5.36e-01	-0.1236
23429	RYBP	A001-C-104	Human	Colorectum	FAP	1.16e-04	-3.47e-01	0.0184
23429	RYBP	A015-C-005	Human	Colorectum	FAP	9.67e-10	-4.17e-01	-0.0336
23429	RYBP	A015-C-006	Human	Colorectum	FAP	5.18e-16	-5.22e-01	-0.0994
23429	RYBP	A015-C-106	Human	Colorectum	FAP	2.85e-09	-3.65e-01	-0.0511
23429	RYBP	A002-C-114	Human	Colorectum	FAP	8.03e-17	-4.51e-01	-0.1561
23429	RYBP	A015-C-104	Human	Colorectum	FAP	1.68e-24	-5.51e-01	-0.1899
23429	RYBP	A001-C-014	Human	Colorectum	FAP	4.70e-10	-3.80e-01	0.0135

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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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
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
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:20000598	Lung	AIS	negative regulation of ubiquitin-dependent protein catabolic process	11/1849	48/18723	6.14e-03	4.98e-02	11
GO:001049820	Oral cavity	OSCC	proteasomal protein catabolic process	336/7305	490/18723	5.45e-41	8.63e-38	336
GO:004316120	Oral cavity	OSCC	proteasome-mediated ubiquitin-dependent protein catabolic process	285/7305	412/18723	5.68e-36	5.99e-33	285
GO:004217620	Oral cavity	OSCC	regulation of protein catabolic process	254/7305	391/18723	1.07e-25	3.22e-23	254
GO:190336220	Oral cavity	OSCC	regulation of cellular protein catabolic process	174/7305	255/18723	2.04e-21	3.70e-19	174
GO:190305020	Oral cavity	OSCC	regulation of proteolysis involved in cellular protein catabolic process	152/7305	221/18723	2.16e-19	3.15e-17	152
GO:006113620	Oral cavity	OSCC	regulation of proteasomal protein catabolic process	132/7305	187/18723	1.57e-18	1.81e-16	132
GO:200005820	Oral cavity	OSCC	regulation of ubiquitin-dependent protein catabolic process	118/7305	164/18723	9.37e-18	9.27e-16	118
GO:00165707	Oral cavity	OSCC	histone modification	270/7305	463/18723	1.59e-17	1.50e-15	270
GO:003243420	Oral cavity	OSCC	regulation of proteasomal ubiquitin-dependent protein catabolic process	100/7305	134/18723	4.72e-17	4.04e-15	100
GO:000989519	Oral cavity	OSCC	negative regulation of catabolic process	180/7305	320/18723	2.44e-10	6.86e-09	180
GO:003133020	Oral cavity	OSCC	negative regulation of cellular catabolic process	152/7305	262/18723	3.04e-10	8.28e-09	152
GO:00165746	Oral cavity	OSCC	histone ubiquitination	38/7305	47/18723	5.22e-09	1.14e-07	38
GO:004217719	Oral cavity	OSCC	negative regulation of protein catabolic process	77/7305	121/18723	3.49e-08	6.64e-07	77
GO:00065135	Oral cavity	OSCC	protein monoubiquitination	47/7305	67/18723	2.32e-07	3.68e-06	47
GO:004586120	Oral cavity	OSCC	negative regulation of proteolysis	181/7305	351/18723	1.01e-06	1.37e-05	181
GO:00103903	Oral cavity	OSCC	histone monoubiquitination	24/7305	29/18723	1.74e-06	2.26e-05	24
GO:200005919	Oral cavity	OSCC	negative regulation of ubiquitin-dependent protein catabolic process	35/7305	48/18723	1.93e-06	2.47e-05	35
GO:190336317	Oral cavity	OSCC	negative regulation of cellular protein catabolic process	49/7305	75/18723	3.49e-06	4.15e-05	49
GO:00335224	Oral cavity	OSCC	histone H2A ubiquitination	21/7305	26/18723	1.66e-05	1.64e-04	21

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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

RYBP

SNV

Missense_Mutation

novel

c.470G>A

p.Val158Ile

p.V158I

Q8N488

protein_coding

deleterious(0)

probably_damaging(0.991)

TCGA-A8-A08R-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

RYBP

SNV

Missense_Mutation

novel

c.247G>C

p.Glu83Asp

p.E83D

Q8N488

protein_coding

tolerated(0.57)

benign(0)

TCGA-AR-A2LH-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

RYBP

insertion

Frame_Shift_Ins

novel

c.459_460insTTCTATTTCATTCTCTTCA

p.Asn155SerfsTer16

p.N155Sfs*16

Q8N488

protein_coding

TCGA-AO-A0J9-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

RYBP

insertion

Nonsense_Mutation

novel

c.458_459insACATAAAGATAGCTTGAGTAAACT

p.Gly154delinsAspIleLysIleAlaTerValAsnCys

p.G154delinsDIKIA*VNC

Q8N488

protein_coding

TCGA-AO-A0J9-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

RYBP

SNV

Missense_Mutation

novel

c.515T>C

p.Ser173Pro

p.S173P

Q8N488

protein_coding

deleterious(0.05)

benign(0.127)

TCGA-AA-A010-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Chemotherapy

folinic

RYBP

SNV

Missense_Mutation

c.407C>T

p.Arg137Trp

p.R137W

Q8N488

protein_coding

deleterious(0.01)

probably_damaging(0.916)

TCGA-AZ-4313-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

RYBP

SNV

Missense_Mutation

novel

c.570N>T

p.Ser191Leu

p.S191L

Q8N488

protein_coding

deleterious(0)

probably_damaging(0.99)

TCGA-AZ-4315-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

RYBP

SNV

Missense_Mutation

novel

c.282N>C

p.Lys95Thr

p.K95T

Q8N488

protein_coding

deleterious(0)

probably_damaging(0.937)

TCGA-CA-6717-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Chemotherapy

oxaliplatin

RYBP

SNV

Missense_Mutation

novel

c.132N>A

p.Pro45His

p.P45H

Q8N488

protein_coding

deleterious(0)

probably_damaging(0.991)

TCGA-A5-A1OF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

RYBP

SNV

Missense_Mutation

novel

c.144N>T

p.Ser49Phe

p.S49F

Q8N488

protein_coding

deleterious(0)

probably_damaging(0.989)

TCGA-AX-A05Z-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

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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