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: TTC17

Gene summary for TTC17

Gene summary.

Gene information	Species	Human
	Gene symbol	TTC17
	Gene ID	55761
	Gene name	tetratricopeptide repeat domain 17
	Gene Alias	TTC17
	Cytomap	11p12-p11.2
	Gene Type	protein-coding
	GO ID	GO:0006996
	UniProtAcc	Q6MZP1

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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
55761	TTC17	C09	Human	Oral cavity	OSCC	2.08e-10	4.65e-01	0.1431
55761	TTC17	LN46	Human	Oral cavity	OSCC	1.86e-08	4.80e-01	0.1666
55761	TTC17	LP15	Human	Oral cavity	LP	1.42e-03	1.01e+00	0.2174
55761	TTC17	EOLP-1	Human	Oral cavity	EOLP	4.15e-09	3.80e-01	-0.0202
55761	TTC17	NEOLP-1	Human	Oral cavity	NEOLP	4.03e-03	3.23e-01	-0.0194
55761	TTC17	NEOLP-2	Human	Oral cavity	NEOLP	6.05e-04	3.00e-01	-0.0196
55761	TTC17	NEOLP-3	Human	Oral cavity	NEOLP	1.17e-05	3.17e-01	-0.0191
55761	TTC17	SYSMH1	Human	Oral cavity	OSCC	1.98e-10	3.18e-01	0.1127
55761	TTC17	SYSMH2	Human	Oral cavity	OSCC	6.94e-08	1.96e-01	0.2326
55761	TTC17	SYSMH3	Human	Oral cavity	OSCC	3.39e-10	3.52e-01	0.2442
55761	TTC17	SYSMH4	Human	Oral cavity	OSCC	3.81e-02	-5.10e-02	0.1226
55761	TTC17	SYSMH5	Human	Oral cavity	OSCC	3.96e-05	2.23e-02	0.0647
55761	TTC17	SYSMH6	Human	Oral cavity	OSCC	2.48e-05	1.50e-01	0.1275
55761	TTC17	HTA12-23-1	Human	Pancreas	PDAC	3.27e-06	8.85e-01	0.3405
55761	TTC17	HTA12-25-1	Human	Pancreas	PDAC	9.78e-06	8.73e-01	0.313
55761	TTC17	HTA12-26-1	Human	Pancreas	PDAC	1.09e-25	1.24e+00	0.3728
55761	TTC17	HTA12-29-1	Human	Pancreas	PDAC	1.33e-64	1.26e+00	0.3722
55761	TTC17	047563_1562-all-cells	Human	Prostate	BPH	4.70e-07	2.33e-01	0.0791
55761	TTC17	048752_1579-all-cells	Human	Prostate	BPH	2.99e-14	5.32e-01	0.1008
55761	TTC17	052095_1628-all-cells	Human	Prostate	BPH	3.91e-22	5.92e-01	0.1032

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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:000701510	Cervix	CC	actin filament organization	109/2311	442/18723	4.92e-13	2.45e-10	109
GO:005125810	Cervix	CC	protein polymerization	70/2311	297/18723	5.20e-08	3.11e-06	70
GO:00081549	Cervix	CC	actin polymerization or depolymerization	51/2311	218/18723	4.05e-06	1.05e-04	51
GO:00300419	Cervix	CC	actin filament polymerization	45/2311	191/18723	1.20e-05	2.54e-04	45
GO:0007015	Colorectum	AD	actin filament organization	167/3918	442/18723	1.65e-16	7.94e-14	167
GO:0008154	Colorectum	AD	actin polymerization or depolymerization	90/3918	218/18723	6.14e-12	8.23e-10	90
GO:0030041	Colorectum	AD	actin filament polymerization	81/3918	191/18723	1.35e-11	1.69e-09	81
GO:0051258	Colorectum	AD	protein polymerization	112/3918	297/18723	1.85e-11	2.27e-09	112
GO:00070151	Colorectum	SER	actin filament organization	134/2897	442/18723	1.39e-15	5.70e-13	134
GO:00081541	Colorectum	SER	actin polymerization or depolymerization	77/2897	218/18723	3.50e-13	1.19e-10	77
GO:00300411	Colorectum	SER	actin filament polymerization	70/2897	191/18723	5.39e-13	1.65e-10	70
GO:00512581	Colorectum	SER	protein polymerization	91/2897	297/18723	2.72e-11	5.06e-09	91
GO:00070152	Colorectum	MSS	actin filament organization	146/3467	442/18723	1.16e-13	2.67e-11	146
GO:00081542	Colorectum	MSS	actin polymerization or depolymerization	79/3467	218/18723	4.14e-10	3.49e-08	79
GO:00300412	Colorectum	MSS	actin filament polymerization	71/3467	191/18723	8.77e-10	6.92e-08	71
GO:00512582	Colorectum	MSS	protein polymerization	97/3467	297/18723	2.98e-09	2.07e-07	97
GO:00070154	Colorectum	FAP	actin filament organization	125/2622	442/18723	1.97e-15	3.03e-12	125
GO:00081544	Colorectum	FAP	actin polymerization or depolymerization	60/2622	218/18723	1.15e-07	7.43e-06	60
GO:00300414	Colorectum	FAP	actin filament polymerization	53/2622	191/18723	4.65e-07	2.46e-05	53
GO:00512584	Colorectum	FAP	protein polymerization	73/2622	297/18723	7.11e-07	3.32e-05	73

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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

TTC17

SNV

Missense_Mutation

novel

c.2908G>T

p.Ala970Ser

p.A970S

Q96AE7

protein_coding

tolerated(0.38)

possibly_damaging(0.551)

TCGA-A2-A25A-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Cytoxan

TTC17

SNV

Missense_Mutation

novel

c.3082A>G

p.Lys1028Glu

p.K1028E

Q96AE7

protein_coding

tolerated(0.18)

probably_damaging(0.98)

TCGA-A2-A3XY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

TTC17

SNV

Missense_Mutation

c.2881G>T

p.Asp961Tyr

p.D961Y

Q96AE7

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TTC17

SNV

Missense_Mutation

c.412N>T

p.Asp138Tyr

p.D138Y

Q96AE7

protein_coding

deleterious(0.02)

possibly_damaging(0.736)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TTC17

SNV

Missense_Mutation

novel

c.3080N>G

p.Val1027Gly

p.V1027G

Q96AE7

protein_coding

deleterious(0)

probably_damaging(0.991)

TCGA-AO-A1KP-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

fluorouracil

TTC17

SNV

Missense_Mutation

c.1552G>A

p.Glu518Lys

p.E518K

Q96AE7

protein_coding

tolerated(0.58)

benign(0.106)

TCGA-AR-A251-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

TTC17

SNV

Missense_Mutation

c.334N>T

p.Pro112Ser

p.P112S

Q96AE7

protein_coding

tolerated(0.28)

benign(0.34)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TTC17

SNV

Missense_Mutation

c.751N>G

p.Arg251Gly

p.R251G

Q96AE7

protein_coding

deleterious(0)

probably_damaging(0.953)

TCGA-C8-A134-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

TTC17

SNV

Missense_Mutation

rs765970018

c.1429N>A

p.Val477Ile

p.V477I

Q96AE7

protein_coding

tolerated(0.39)

benign(0.06)

TCGA-EW-A1IZ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

taxotere

TTC17

insertion

Frame_Shift_Ins

novel

c.2137_2138insTATTATATATTAGTCTTTT

p.Arg713IlefsTer20

p.R713Ifs*20

Q96AE7

protein_coding

TCGA-A8-A07L-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

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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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