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: ANKIB1

Gene summary for ANKIB1

Gene summary.

Gene information	Species	Human
	Gene symbol	ANKIB1
	Gene ID	54467
	Gene name	ankyrin repeat and IBR domain containing 1
	Gene Alias	ANKIB1
	Cytomap	7q21.2
	Gene Type	protein-coding
	GO ID	GO:0000209
	UniProtAcc	Q9P2G1

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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
54467	ANKIB1	CCI_1	Human	Cervix	CC	5.83e-04	6.78e-01	0.528
54467	ANKIB1	CCI_2	Human	Cervix	CC	1.11e-08	9.81e-01	0.5249
54467	ANKIB1	CCI_3	Human	Cervix	CC	9.73e-13	9.70e-01	0.516
54467	ANKIB1	HTA11_3410_2000001011	Human	Colorectum	AD	1.33e-09	-4.24e-01	0.0155
54467	ANKIB1	HTA11_3361_2000001011	Human	Colorectum	AD	3.17e-06	-6.09e-01	-0.1207
54467	ANKIB1	HTA11_866_2000001011	Human	Colorectum	AD	3.63e-02	-2.22e-01	-0.1001
54467	ANKIB1	HTA11_5212_2000001011	Human	Colorectum	AD	1.46e-04	-6.06e-01	-0.2061
54467	ANKIB1	HTA11_5216_2000001011	Human	Colorectum	SER	7.39e-04	-7.97e-01	-0.1462
54467	ANKIB1	HTA11_99999970781_79442	Human	Colorectum	MSS	9.71e-05	-1.70e-01	0.294
54467	ANKIB1	HTA11_99999965104_69814	Human	Colorectum	MSS	5.54e-04	6.00e-01	0.281
54467	ANKIB1	HTA11_99999974143_84620	Human	Colorectum	MSS	1.16e-08	-4.14e-01	0.3005
54467	ANKIB1	F007	Human	Colorectum	FAP	4.17e-02	-2.33e-01	0.1176
54467	ANKIB1	A001-C-207	Human	Colorectum	FAP	4.18e-06	-2.85e-01	0.1278
54467	ANKIB1	A015-C-203	Human	Colorectum	FAP	1.37e-25	-4.02e-01	-0.1294
54467	ANKIB1	A015-C-204	Human	Colorectum	FAP	6.81e-10	-4.28e-01	-0.0228
54467	ANKIB1	A014-C-040	Human	Colorectum	FAP	2.59e-07	-5.67e-01	-0.1184
54467	ANKIB1	A002-C-201	Human	Colorectum	FAP	3.91e-17	-3.73e-01	0.0324
54467	ANKIB1	A001-C-119	Human	Colorectum	FAP	2.24e-06	-3.58e-01	-0.1557
54467	ANKIB1	A001-C-108	Human	Colorectum	FAP	1.97e-13	-2.88e-01	-0.0272
54467	ANKIB1	A002-C-205	Human	Colorectum	FAP	1.43e-25	-4.73e-01	-0.1236

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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:004217610	Cervix	CC	regulation of protein catabolic process	104/2311	391/18723	9.39e-15	9.36e-12	104
GO:004586210	Cervix	CC	positive regulation of proteolysis	95/2311	372/18723	1.84e-12	6.86e-10	95
GO:190336210	Cervix	CC	regulation of cellular protein catabolic process	72/2311	255/18723	5.98e-12	2.10e-09	72
GO:004573210	Cervix	CC	positive regulation of protein catabolic process	65/2311	231/18723	7.44e-11	1.39e-08	65
GO:001049810	Cervix	CC	proteasomal protein catabolic process	111/2311	490/18723	8.98e-11	1.58e-08	111
GO:000989610	Cervix	CC	positive regulation of catabolic process	109/2311	492/18723	5.26e-10	6.99e-08	109
GO:190305010	Cervix	CC	regulation of proteolysis involved in cellular protein catabolic process	60/2311	221/18723	1.82e-09	1.98e-07	60
GO:200005810	Cervix	CC	regulation of ubiquitin-dependent protein catabolic process	47/2311	164/18723	1.63e-08	1.25e-06	47
GO:004316110	Cervix	CC	proteasome-mediated ubiquitin-dependent protein catabolic process	91/2311	412/18723	1.65e-08	1.25e-06	91
GO:003133110	Cervix	CC	positive regulation of cellular catabolic process	91/2311	427/18723	9.64e-08	5.25e-06	91
GO:00002097	Cervix	CC	protein polyubiquitination	58/2311	236/18723	1.57e-07	7.41e-06	58
GO:190336410	Cervix	CC	positive regulation of cellular protein catabolic process	43/2311	155/18723	1.80e-07	8.28e-06	43
GO:006113610	Cervix	CC	regulation of proteasomal protein catabolic process	48/2311	187/18723	4.63e-07	1.77e-05	48
GO:003243410	Cervix	CC	regulation of proteasomal ubiquitin-dependent protein catabolic process	38/2311	134/18723	4.99e-07	1.88e-05	38
GO:19030528	Cervix	CC	positive regulation of proteolysis involved in cellular protein catabolic process	34/2311	133/18723	2.28e-05	4.01e-04	34
GO:200006010	Cervix	CC	positive regulation of ubiquitin-dependent protein catabolic process	29/2311	107/18723	2.77e-05	4.62e-04	29
GO:00324369	Cervix	CC	positive regulation of proteasomal ubiquitin-dependent protein catabolic process	25/2311	90/18723	6.22e-05	8.90e-04	25
GO:19018008	Cervix	CC	positive regulation of proteasomal protein catabolic process	29/2311	114/18723	9.71e-05	1.27e-03	29
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

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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

ANKIB1

SNV

Missense_Mutation

novel

c.898N>T

p.Asp300Tyr

p.D300Y

Q9P2G1

protein_coding

deleterious(0)

probably_damaging(0.921)

TCGA-A2-A25A-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Cytoxan

ANKIB1

SNV

Missense_Mutation

novel

c.2602N>T

p.Gly868Trp

p.G868W

Q9P2G1

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.936)

TCGA-A7-A0DB-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

ANKIB1

SNV

Missense_Mutation

novel

c.733N>T

p.Ala245Ser

p.A245S

Q9P2G1

protein_coding

tolerated(0.35)

possibly_damaging(0.473)

TCGA-A7-A3J1-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

anastrazole

ANKIB1

SNV

Missense_Mutation

c.1879N>C

p.Glu627Gln

p.E627Q

Q9P2G1

protein_coding

tolerated(0.23)

benign(0.387)

TCGA-D8-A1JA-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

ANKIB1

SNV

Missense_Mutation

rs191723687

c.613N>T

p.Arg205Trp

p.R205W

Q9P2G1

protein_coding

deleterious(0.02)

possibly_damaging(0.862)

TCGA-D8-A1Y1-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

tamoxiphen

ANKIB1

SNV

Missense_Mutation

novel

c.798N>T

p.Arg266Ser

p.R266S

Q9P2G1

protein_coding

tolerated(0.08)

probably_damaging(0.917)

TCGA-EW-A1P7-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

ANKIB1

SNV

Missense_Mutation

rs748508968

c.460N>T

p.Ala154Ser

p.A154S

Q9P2G1

protein_coding

tolerated(0.06)

possibly_damaging(0.578)

TCGA-EW-A1PD-01

Breast

breast invasive carcinoma

Male

<65

I/II

Chemotherapy

docetaxel

ANKIB1

SNV

Missense_Mutation

novel

c.2888N>G

p.Pro963Arg

p.P963R

Q9P2G1

protein_coding

deleterious_low_confidence(0.02)

benign(0.1)

TCGA-LL-A5YP-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

ANKIB1

insertion

Frame_Shift_Ins

novel

c.2972_2973insGCTTTCCTATTTCTTCCTTCCATTCT

p.Thr992LeufsTer9

p.T992Lfs*9

Q9P2G1

protein_coding

TCGA-A8-A09E-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

anastrozole

ANKIB1

insertion

Frame_Shift_Ins

rs201434379

c.429_430insA

p.Asn146LysfsTer29

p.N146Kfs*29

Q9P2G1

protein_coding

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

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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