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: DENND1B

Gene summary for DENND1B

Gene summary.

Gene information	Species	Human
	Gene symbol	DENND1B
	Gene ID	163486
	Gene name	DENN domain containing 1B
	Gene Alias	C1ORF18
	Cytomap	1q31.3
	Gene Type	protein-coding
	GO ID	GO:0001816
	UniProtAcc	Q6P3S1

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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
163486	DENND1B	GSM4909307	Human	Breast	IDC	3.61e-16	4.33e-01	0.1569
163486	DENND1B	GSM4909308	Human	Breast	IDC	7.21e-43	7.41e-01	0.158
163486	DENND1B	M5	Human	Breast	IDC	1.46e-15	1.03e+00	0.1598
163486	DENND1B	P3	Human	Breast	IDC	4.18e-02	4.13e-01	0.1542
163486	DENND1B	DCIS2	Human	Breast	DCIS	8.38e-40	1.97e-01	0.0085
163486	DENND1B	CCI_1	Human	Cervix	CC	4.23e-12	2.05e+00	0.528
163486	DENND1B	CCI_3	Human	Cervix	CC	2.94e-16	1.15e+00	0.516
163486	DENND1B	HTA11_3410_2000001011	Human	Colorectum	AD	1.93e-37	-9.53e-01	0.0155
163486	DENND1B	HTA11_2487_2000001011	Human	Colorectum	SER	1.58e-06	-5.54e-01	-0.1808
163486	DENND1B	HTA11_2951_2000001011	Human	Colorectum	AD	1.43e-02	-8.48e-01	0.0216
163486	DENND1B	HTA11_3361_2000001011	Human	Colorectum	AD	4.22e-10	-7.86e-01	-0.1207
163486	DENND1B	HTA11_696_2000001011	Human	Colorectum	AD	4.65e-16	-5.21e-01	-0.1464
163486	DENND1B	HTA11_866_2000001011	Human	Colorectum	AD	5.91e-08	-4.55e-01	-0.1001
163486	DENND1B	HTA11_1391_2000001011	Human	Colorectum	AD	3.66e-02	-4.72e-01	-0.059
163486	DENND1B	HTA11_5212_2000001011	Human	Colorectum	AD	2.16e-04	-7.94e-01	-0.2061
163486	DENND1B	HTA11_5216_2000001011	Human	Colorectum	SER	1.86e-02	-7.41e-01	-0.1462
163486	DENND1B	HTA11_7862_2000001011	Human	Colorectum	AD	2.93e-02	-4.36e-01	-0.0179
163486	DENND1B	HTA11_866_3004761011	Human	Colorectum	AD	1.69e-26	-8.32e-01	0.096
163486	DENND1B	HTA11_8622_2000001021	Human	Colorectum	SER	5.25e-08	-9.09e-01	0.0528
163486	DENND1B	HTA11_10711_2000001011	Human	Colorectum	AD	1.94e-10	-7.77e-01	0.0338

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
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

∗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:000181911	Breast	IDC	positive regulation of cytokine production	61/1434	467/18723	2.81e-05	6.58e-04	61
GO:000271111	Breast	IDC	positive regulation of T cell mediated immunity	13/1434	56/18723	2.48e-04	3.87e-03	13
GO:00508521	Breast	IDC	T cell receptor signaling pathway	20/1434	123/18723	1.05e-03	1.16e-02	20
GO:000270911	Breast	IDC	regulation of T cell mediated immunity	14/1434	85/18723	4.98e-03	3.77e-02	14
GO:00022532	Breast	IDC	activation of immune response	43/1434	375/18723	5.16e-03	3.84e-02	43
GO:000181921	Breast	DCIS	positive regulation of cytokine production	63/1390	467/18723	2.76e-06	9.42e-05	63
GO:000271121	Breast	DCIS	positive regulation of T cell mediated immunity	13/1390	56/18723	1.82e-04	2.98e-03	13
GO:00508522	Breast	DCIS	T cell receptor signaling pathway	20/1390	123/18723	7.14e-04	8.56e-03	20
GO:000225311	Breast	DCIS	activation of immune response	43/1390	375/18723	2.96e-03	2.54e-02	43
GO:000270921	Breast	DCIS	regulation of T cell mediated immunity	14/1390	85/18723	3.78e-03	3.03e-02	14
GO:000245612	Breast	DCIS	T cell mediated immunity	16/1390	109/18723	6.56e-03	4.60e-02	16
GO:00430877	Cervix	CC	regulation of GTPase activity	79/2311	348/18723	4.21e-08	2.60e-06	79
GO:00027644	Cervix	CC	immune response-regulating signaling pathway	97/2311	468/18723	1.49e-07	7.07e-06	97
GO:00018197	Cervix	CC	positive regulation of cytokine production	95/2311	467/18723	4.88e-07	1.85e-05	95
GO:00988767	Cervix	CC	vesicle-mediated transport to the plasma membrane	34/2311	136/18723	3.75e-05	5.91e-04	34
GO:00022533	Cervix	CC	activation of immune response	72/2311	375/18723	8.26e-05	1.11e-03	72
GO:00435476	Cervix	CC	positive regulation of GTPase activity	53/2311	255/18723	8.72e-05	1.16e-03	53
GO:00161977	Cervix	CC	endosomal transport	48/2311	230/18723	1.65e-04	1.97e-03	48
GO:00024564	Cervix	CC	T cell mediated immunity	26/2311	109/18723	6.39e-04	5.97e-03	26
GO:0002768	Cervix	CC	immune response-regulating cell surface receptor signaling pathway	59/2311	315/18723	6.64e-04	6.11e-03	59

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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

DENND1B

SNV

Missense_Mutation

rs756637931

c.263N>T

p.Thr88Met

p.T88M

Q6P3S1

protein_coding

deleterious(0)

possibly_damaging(0.635)

TCGA-A1-A0SO-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

DENND1B

SNV

Missense_Mutation

c.650N>G

p.Ile217Ser

p.I217S

Q6P3S1

protein_coding

deleterious(0)

possibly_damaging(0.802)

TCGA-A8-A06U-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

DENND1B

SNV

Missense_Mutation

c.976N>A

p.Val326Ile

p.V326I

Q6P3S1

protein_coding

deleterious(0.01)

possibly_damaging(0.646)

TCGA-A8-A07L-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

DENND1B

SNV

Missense_Mutation

novel

c.2139N>A

p.Asp713Glu

p.D713E

Q6P3S1

protein_coding

tolerated_low_confidence(0.13)

possibly_damaging(0.647)

TCGA-A8-A09W-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

DENND1B

SNV

Missense_Mutation

novel

c.1623A>C

p.Glu541Asp

p.E541D

Q6P3S1

protein_coding

tolerated(0.15)

benign(0.088)

TCGA-AO-A0JB-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

DENND1B

SNV

Missense_Mutation

novel

c.1958N>G

p.Ser653Cys

p.S653C

Q6P3S1

protein_coding

tolerated(0.06)

probably_damaging(0.965)

TCGA-BH-A0DZ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

docetaxel

DENND1B

SNV

Missense_Mutation

rs757972002

c.1903N>A

p.Asp635Asn

p.D635N

Q6P3S1

protein_coding

deleterious(0)

probably_damaging(0.974)

TCGA-BH-A0HA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

DENND1B

SNV

Missense_Mutation

rs371428108

c.2272G>A

p.Asp758Asn

p.D758N

Q6P3S1

protein_coding

tolerated_low_confidence(0.09)

benign(0.062)

TCGA-E2-A1B1-01

Breast

breast invasive carcinoma

Female

<65

I/II

Other, specify in notesbiphosphonate

zoledronic

DENND1B

SNV

Missense_Mutation

novel

c.988N>A

p.Phe330Ile

p.F330I

Q6P3S1

protein_coding

deleterious(0)

probably_damaging(0.967)

TCGA-UU-A93S-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

DENND1B

insertion

Frame_Shift_Ins

novel

c.1842_1843insCTGA

p.Asn615LeufsTer12

p.N615Lfs*12

Q6P3S1

protein_coding

TCGA-AO-A128-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

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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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