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: ZYG11B

Gene summary for ZYG11B

Gene summary.

Gene information	Species	Human
	Gene symbol	ZYG11B
	Gene ID	79699
	Gene name	zyg-11 family member B, cell cycle regulator
	Gene Alias	ZYG11
	Cytomap	1p32.3
	Gene Type	protein-coding
	GO ID	GO:0006508
	UniProtAcc	B4DK95

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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
79699	ZYG11B	HTA11_347_2000001011	Human	Colorectum	AD	1.98e-09	4.69e-01	-0.1954
79699	ZYG11B	HTA11_1391_2000001011	Human	Colorectum	AD	4.91e-03	4.13e-01	-0.059
79699	ZYG11B	HTA11_7663_2000001011	Human	Colorectum	SER	1.40e-09	9.40e-01	0.0131
79699	ZYG11B	HTA11_6818_2000001011	Human	Colorectum	AD	2.34e-03	5.88e-01	0.0112
79699	ZYG11B	HTA11_99999965062_69753	Human	Colorectum	MSI-H	1.69e-06	1.12e+00	0.3487
79699	ZYG11B	HTA11_99999965104_69814	Human	Colorectum	MSS	1.77e-08	6.79e-01	0.281
79699	ZYG11B	HTA11_99999971662_82457	Human	Colorectum	MSS	9.71e-24	1.34e+00	0.3859
79699	ZYG11B	HTA11_99999973899_84307	Human	Colorectum	MSS	4.31e-04	5.48e-01	0.2585
79699	ZYG11B	A015-C-203	Human	Colorectum	FAP	3.83e-12	-2.44e-01	-0.1294
79699	ZYG11B	A015-C-204	Human	Colorectum	FAP	1.35e-02	-2.57e-01	-0.0228
79699	ZYG11B	A002-C-201	Human	Colorectum	FAP	5.82e-05	-1.93e-01	0.0324
79699	ZYG11B	A002-C-203	Human	Colorectum	FAP	2.31e-02	-1.44e-01	0.2786
79699	ZYG11B	A001-C-119	Human	Colorectum	FAP	1.80e-02	-2.55e-01	-0.1557
79699	ZYG11B	A001-C-108	Human	Colorectum	FAP	6.07e-11	-2.73e-01	-0.0272
79699	ZYG11B	A002-C-205	Human	Colorectum	FAP	1.67e-07	-1.88e-01	-0.1236
79699	ZYG11B	A001-C-104	Human	Colorectum	FAP	1.01e-02	-2.11e-01	0.0184
79699	ZYG11B	A015-C-006	Human	Colorectum	FAP	1.45e-07	-3.35e-01	-0.0994
79699	ZYG11B	A015-C-106	Human	Colorectum	FAP	6.44e-05	-2.12e-01	-0.0511
79699	ZYG11B	A002-C-114	Human	Colorectum	FAP	2.24e-08	-3.32e-01	-0.1561
79699	ZYG11B	A015-C-104	Human	Colorectum	FAP	1.53e-11	-2.75e-01	-0.1899

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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
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
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:0042176	Colorectum	AD	regulation of protein catabolic process	160/3918	391/18723	1.06e-19	7.34e-17	160
GO:0009896	Colorectum	AD	positive regulation of catabolic process	180/3918	492/18723	4.33e-16	1.94e-13	180
GO:1903362	Colorectum	AD	regulation of cellular protein catabolic process	109/3918	255/18723	2.14e-15	6.08e-13	109
GO:0010498	Colorectum	AD	proteasomal protein catabolic process	174/3918	490/18723	3.18e-14	7.66e-12	174
GO:0031331	Colorectum	AD	positive regulation of cellular catabolic process	156/3918	427/18723	4.68e-14	1.05e-11	156
GO:1903050	Colorectum	AD	regulation of proteolysis involved in cellular protein catabolic process	92/3918	221/18723	2.04e-12	3.19e-10	92
GO:0045732	Colorectum	AD	positive regulation of protein catabolic process	92/3918	231/18723	3.85e-11	4.47e-09	92
GO:0043161	Colorectum	AD	proteasome-mediated ubiquitin-dependent protein catabolic process	141/3918	412/18723	1.77e-10	1.68e-08	141
GO:0045862	Colorectum	AD	positive regulation of proteolysis	129/3918	372/18723	4.04e-10	3.46e-08	129
GO:0061136	Colorectum	AD	regulation of proteasomal protein catabolic process	75/3918	187/18723	1.65e-09	1.20e-07	75
GO:2000058	Colorectum	AD	regulation of ubiquitin-dependent protein catabolic process	68/3918	164/18723	1.82e-09	1.31e-07	68
GO:1903364	Colorectum	AD	positive regulation of cellular protein catabolic process	62/3918	155/18723	4.66e-08	2.51e-06	62
GO:0032434	Colorectum	AD	regulation of proteasomal ubiquitin-dependent protein catabolic process	54/3918	134/18723	2.51e-07	1.02e-05	54
GO:1903052	Colorectum	AD	positive regulation of proteolysis involved in cellular protein catabolic process	53/3918	133/18723	4.93e-07	1.85e-05	53
GO:2000060	Colorectum	AD	positive regulation of ubiquitin-dependent protein catabolic process	44/3918	107/18723	1.65e-06	5.03e-05	44
GO:1901800	Colorectum	AD	positive regulation of proteasomal protein catabolic process	44/3918	114/18723	1.18e-05	2.62e-04	44
GO:0032436	Colorectum	AD	positive regulation of proteasomal ubiquitin-dependent protein catabolic process	36/3918	90/18723	2.89e-05	5.37e-04	36
GO:0006515	Colorectum	AD	protein quality control for misfolded or incompletely synthesized proteins	14/3918	28/18723	6.01e-04	6.33e-03	14
GO:00421761	Colorectum	SER	regulation of protein catabolic process	126/2897	391/18723	5.33e-17	2.52e-14	126
GO:19033621	Colorectum	SER	regulation of cellular protein catabolic process	91/2897	255/18723	1.22e-15	5.36e-13	91

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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

ZYG11B

SNV

Missense_Mutation

novel

c.1542G>T

p.Leu514Phe

p.L514F

Q9C0D3

protein_coding

tolerated(0.19)

benign(0.125)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ZYG11B

SNV

Missense_Mutation

novel

c.1555N>G

p.Ser519Gly

p.S519G

Q9C0D3

protein_coding

deleterious(0.01)

possibly_damaging(0.571)

TCGA-AO-A128-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

ZYG11B

SNV

Missense_Mutation

novel

c.143G>C

p.Gly48Ala

p.G48A

Q9C0D3

protein_coding

tolerated(0.96)

benign(0.001)

TCGA-GI-A2C9-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

ZYG11B

insertion

Frame_Shift_Ins

novel

c.2018_2019insGT

p.Met674SerfsTer17

p.M674Sfs*17

Q9C0D3

protein_coding

TCGA-A8-A08F-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

5-fluorouracil

ZYG11B

insertion

Nonsense_Mutation

novel

c.2019_2020insTCAAATAAATAAATAAATGTAAAA

p.Ala673_Met674insSerAsnLysTerIleAsnValLys

p.A673_M674insSNK*INVK

Q9C0D3

protein_coding

TCGA-A8-A08F-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

5-fluorouracil

ZYG11B

insertion

Frame_Shift_Ins

novel

c.1166_1167insGTGTGTATATACATCTATACATATATGTGTATATACAT

p.Asn389LysfsTer15

p.N389Kfs*15

Q9C0D3

protein_coding

TCGA-BH-A0B4-01

Breast

breast invasive carcinoma

Male

>=65

III/IV

Hormone Therapy

tamoxiphen

ZYG11B

SNV

Missense_Mutation

novel

c.572T>C

p.Leu191Ser

p.L191S

Q9C0D3

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

ZYG11B

SNV

Missense_Mutation

novel

c.934G>A

p.Gly312Ser

p.G312S

Q9C0D3

protein_coding

tolerated(0.55)

benign(0.041)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

ZYG11B

SNV

Missense_Mutation

c.2107G>T

p.Asp703Tyr

p.D703Y

Q9C0D3

protein_coding

deleterious(0.01)

benign(0.179)

TCGA-FU-A3HZ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

ZYG11B

SNV

Missense_Mutation

c.91N>C

p.Glu31Gln

p.E31Q

Q9C0D3

protein_coding

deleterious(0.03)

probably_damaging(0.943)

TCGA-JX-A3Q0-01

Cervix

cervical & endocervical cancer

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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