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: TBC1D5

Gene summary for TBC1D5

Gene summary.

Gene information	Species	Human
	Gene symbol	TBC1D5
	Gene ID	9779
	Gene name	TBC1 domain family member 5
	Gene Alias	TBC1D5
	Cytomap	3p24.3
	Gene Type	protein-coding
	GO ID	GO:0002090
	UniProtAcc	Q92609

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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
9779	TBC1D5	CCI_1	Human	Cervix	CC	7.31e-04	8.11e-01	0.528
9779	TBC1D5	CCI_3	Human	Cervix	CC	1.29e-11	1.49e+00	0.516
9779	TBC1D5	sample3	Human	Cervix	CC	2.20e-02	-1.99e-01	0.1387
9779	TBC1D5	T3	Human	Cervix	CC	3.48e-04	-1.94e-01	0.1389
9779	TBC1D5	HTA11_2487_2000001011	Human	Colorectum	SER	1.07e-02	-4.68e-01	-0.1808
9779	TBC1D5	HTA11_347_2000001011	Human	Colorectum	AD	4.77e-07	5.33e-01	-0.1954
9779	TBC1D5	HTA11_2112_2000001011	Human	Colorectum	SER	4.21e-02	-5.84e-01	-0.2196
9779	TBC1D5	HTA11_5212_2000001011	Human	Colorectum	AD	4.81e-03	-6.42e-01	-0.2061
9779	TBC1D5	HTA11_5216_2000001011	Human	Colorectum	SER	1.95e-08	-6.21e-01	-0.1462
9779	TBC1D5	HTA11_866_3004761011	Human	Colorectum	AD	5.53e-03	-3.74e-01	0.096
9779	TBC1D5	HTA11_99999965062_69753	Human	Colorectum	MSI-H	9.04e-13	1.10e+00	0.3487
9779	TBC1D5	HTA11_99999965104_69814	Human	Colorectum	MSS	1.53e-06	6.19e-01	0.281
9779	TBC1D5	HTA11_99999973899_84307	Human	Colorectum	MSS	2.02e-06	-5.32e-01	0.2585
9779	TBC1D5	HTA11_99999974143_84620	Human	Colorectum	MSS	4.41e-15	-5.15e-01	0.3005
9779	TBC1D5	A015-C-203	Human	Colorectum	FAP	5.06e-38	-5.20e-01	-0.1294
9779	TBC1D5	A015-C-204	Human	Colorectum	FAP	3.78e-05	-1.79e-01	-0.0228
9779	TBC1D5	A014-C-040	Human	Colorectum	FAP	1.58e-03	-3.11e-01	-0.1184
9779	TBC1D5	A002-C-201	Human	Colorectum	FAP	1.54e-14	-4.16e-01	0.0324
9779	TBC1D5	A001-C-119	Human	Colorectum	FAP	5.59e-11	-5.49e-01	-0.1557
9779	TBC1D5	A001-C-108	Human	Colorectum	FAP	2.33e-15	-2.56e-01	-0.0272

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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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
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:004825915	Oral cavity	EOLP	regulation of receptor-mediated endocytosis	28/2218	110/18723	6.12e-05	7.68e-04	28
GO:004308714	Oral cavity	EOLP	regulation of GTPase activity	66/2218	348/18723	6.92e-05	8.55e-04	66
GO:004311223	Oral cavity	EOLP	receptor metabolic process	37/2218	166/18723	1.00e-04	1.14e-03	37
GO:004259422	Oral cavity	EOLP	response to starvation	42/2218	197/18723	1.03e-04	1.17e-03	42
GO:003166725	Oral cavity	EOLP	response to nutrient levels	82/2218	474/18723	2.59e-04	2.52e-03	82
GO:001619722	Oral cavity	EOLP	endosomal transport	45/2218	230/18723	4.63e-04	4.07e-03	45
GO:00435479	Oral cavity	EOLP	positive regulation of GTPase activity	47/2218	255/18723	1.34e-03	9.33e-03	47
GO:004214722	Oral cavity	EOLP	retrograde transport, endosome to Golgi	21/2218	91/18723	1.89e-03	1.21e-02	21
GO:00482609	Oral cavity	EOLP	positive regulation of receptor-mediated endocytosis	14/2218	52/18723	2.31e-03	1.42e-02	14
GO:003162314	Oral cavity	EOLP	receptor internalization	23/2218	113/18723	6.37e-03	3.15e-02	23
GO:004311231	Oral cavity	NEOLP	receptor metabolic process	40/2005	166/18723	6.24e-07	1.82e-05	40
GO:003010031	Oral cavity	NEOLP	regulation of endocytosis	47/2005	211/18723	7.96e-07	2.20e-05	47
GO:000689831	Oral cavity	NEOLP	receptor-mediated endocytosis	51/2005	244/18723	2.08e-06	4.87e-05	51
GO:004580731	Oral cavity	NEOLP	positive regulation of endocytosis	27/2005	100/18723	4.19e-06	9.05e-05	27
GO:001623631	Oral cavity	NEOLP	macroautophagy	54/2005	291/18723	3.95e-05	5.62e-04	54
GO:003162322	Oral cavity	NEOLP	receptor internalization	26/2005	113/18723	1.24e-04	1.47e-03	26
GO:003166732	Oral cavity	NEOLP	response to nutrient levels	77/2005	474/18723	1.27e-04	1.49e-03	77
GO:004825923	Oral cavity	NEOLP	regulation of receptor-mediated endocytosis	25/2005	110/18723	2.04e-04	2.19e-03	25
GO:001619731	Oral cavity	NEOLP	endosomal transport	41/2005	230/18723	7.41e-04	6.05e-03	41
GO:004826015	Oral cavity	NEOLP	positive regulation of receptor-mediated endocytosis	14/2005	52/18723	8.66e-04	6.83e-03	14

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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

TBC1D5

SNV

Missense_Mutation

c.2287C>A

p.Leu763Ile

p.L763I

Q92609

protein_coding

tolerated_low_confidence(0.41)

benign(0)

TCGA-A8-A07W-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

exemestane

TBC1D5

SNV

Missense_Mutation

c.2047G>C

p.Glu683Gln

p.E683Q

Q92609

protein_coding

deleterious(0)

probably_damaging(0.981)

TCGA-C8-A12T-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

TBC1D5

SNV

Missense_Mutation

c.819N>C

p.Gln273His

p.Q273H

Q92609

protein_coding

tolerated(0.1)

possibly_damaging(0.747)

TCGA-D8-A1JA-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

TBC1D5

SNV

Missense_Mutation

c.2021C>T

p.Ser674Phe

p.S674F

Q92609

protein_coding

deleterious(0)

possibly_damaging(0.656)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

TBC1D5

SNV

Missense_Mutation

novel

c.1423C>T

p.Pro475Ser

p.P475S

Q92609

protein_coding

tolerated(0.99)

benign(0.001)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

TBC1D5

SNV

Missense_Mutation

c.100N>C

p.Asp34His

p.D34H

Q92609

protein_coding

deleterious_low_confidence(0.05)

benign(0.215)

TCGA-4J-AA1J-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

TBC1D5

SNV

Missense_Mutation

c.1376N>G

p.Asn459Ser

p.N459S

Q92609

protein_coding

tolerated(1)

benign(0.003)

TCGA-C5-A1BN-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

TBC1D5

SNV

Missense_Mutation

c.2291N>A

p.Arg764Lys

p.R764K

Q92609

protein_coding

tolerated_low_confidence(0.36)

benign(0)

TCGA-C5-A1BQ-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

cisplatin

TBC1D5

SNV

Missense_Mutation

c.34N>G

p.Leu12Val

p.L12V

Q92609

protein_coding

deleterious_low_confidence(0.01)

probably_damaging(0.994)

TCGA-C5-A1BQ-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

cisplatin

TBC1D5

SNV

Missense_Mutation

c.2291N>A

p.Arg764Lys

p.R764K

Q92609

protein_coding

tolerated_low_confidence(0.36)

benign(0)

TCGA-C5-A3HL-01

Cervix

cervical & endocervical cancer

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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