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: CLTC

Gene summary for CLTC

Gene summary.

Gene information	Species	Human
	Gene symbol	CLTC
	Gene ID	1213
	Gene name	clathrin heavy chain
	Gene Alias	CHC
	Cytomap	17q23.1
	Gene Type	protein-coding
	GO ID	GO:0000041
	UniProtAcc	A0A087WVQ6

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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
1213	CLTC	DCIS2	Human	Breast	DCIS	5.94e-51	2.63e-01	0.0085
1213	CLTC	HTA11_3410_2000001011	Human	Colorectum	AD	4.80e-15	-5.24e-01	0.0155
1213	CLTC	HTA11_347_2000001011	Human	Colorectum	AD	2.64e-13	6.63e-01	-0.1954
1213	CLTC	HTA11_6801_2000001011	Human	Colorectum	SER	5.09e-03	5.86e-01	0.0171
1213	CLTC	HTA11_99999965062_69753	Human	Colorectum	MSI-H	8.81e-08	7.46e-01	0.3487
1213	CLTC	HTA11_99999965104_69814	Human	Colorectum	MSS	3.03e-06	6.54e-01	0.281
1213	CLTC	F007	Human	Colorectum	FAP	4.55e-05	-4.10e-01	0.1176
1213	CLTC	A002-C-010	Human	Colorectum	FAP	4.21e-03	-2.34e-01	0.242
1213	CLTC	A001-C-207	Human	Colorectum	FAP	2.93e-08	-4.25e-01	0.1278
1213	CLTC	A015-C-203	Human	Colorectum	FAP	1.16e-33	-5.33e-01	-0.1294
1213	CLTC	A015-C-204	Human	Colorectum	FAP	1.35e-10	-4.60e-01	-0.0228
1213	CLTC	A014-C-040	Human	Colorectum	FAP	4.12e-07	-5.46e-01	-0.1184
1213	CLTC	A002-C-201	Human	Colorectum	FAP	1.40e-23	-5.91e-01	0.0324
1213	CLTC	A002-C-203	Human	Colorectum	FAP	2.17e-11	-4.03e-01	0.2786
1213	CLTC	A001-C-119	Human	Colorectum	FAP	9.13e-12	-5.37e-01	-0.1557
1213	CLTC	A001-C-108	Human	Colorectum	FAP	1.50e-24	-4.77e-01	-0.0272
1213	CLTC	A002-C-205	Human	Colorectum	FAP	1.58e-30	-5.56e-01	-0.1236
1213	CLTC	A001-C-104	Human	Colorectum	FAP	8.54e-11	-4.24e-01	0.0184
1213	CLTC	A015-C-005	Human	Colorectum	FAP	4.44e-07	-3.75e-01	-0.0336
1213	CLTC	A015-C-006	Human	Colorectum	FAP	6.41e-21	-6.02e-01	-0.0994

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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
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
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:00016496	Breast	Precancer	osteoblast differentiation	27/1080	229/18723	3.35e-04	4.73e-03	27
GO:00068986	Breast	Precancer	receptor-mediated endocytosis	27/1080	244/18723	9.01e-04	1.03e-02	27
GO:00316235	Breast	Precancer	receptor internalization	15/1080	113/18723	2.11e-03	2.00e-02	15
GO:00482685	Breast	Precancer	clathrin coat assembly	5/1080	18/18723	2.88e-03	2.49e-02	5
GO:19043757	Breast	Precancer	regulation of protein localization to cell periphery	15/1080	125/18723	5.58e-03	4.07e-02	15
GO:00068263	Breast	Precancer	iron ion transport	9/1080	58/18723	5.67e-03	4.08e-02	9
GO:19054757	Breast	Precancer	regulation of protein localization to membrane	19/1080	175/18723	5.98e-03	4.22e-02	19
GO:19030767	Breast	Precancer	regulation of protein localization to plasma membrane	13/1080	104/18723	6.79e-03	4.65e-02	13
GO:00000412	Breast	Precancer	transition metal ion transport	13/1080	105/18723	7.35e-03	4.89e-02	13
GO:00015036	Breast	Precancer	ossification	36/1080	408/18723	7.53e-03	4.98e-02	36
GO:000164912	Breast	IDC	osteoblast differentiation	35/1434	229/18723	6.64e-05	1.35e-03	35
GO:190547513	Breast	IDC	regulation of protein localization to membrane	28/1434	175/18723	1.56e-04	2.71e-03	28
GO:000689813	Breast	IDC	receptor-mediated endocytosis	35/1434	244/18723	2.38e-04	3.75e-03	35
GO:000150311	Breast	IDC	ossification	50/1434	408/18723	6.51e-04	8.04e-03	50
GO:003162311	Breast	IDC	receptor internalization	19/1434	113/18723	9.17e-04	1.05e-02	19
GO:190307613	Breast	IDC	regulation of protein localization to plasma membrane	17/1434	104/18723	2.28e-03	2.09e-02	17
GO:190437513	Breast	IDC	regulation of protein localization to cell periphery	19/1434	125/18723	3.06e-03	2.60e-02	19
GO:00431126	Breast	IDC	receptor metabolic process	23/1434	166/18723	4.04e-03	3.25e-02	23
GO:000682611	Breast	IDC	iron ion transport	11/1434	58/18723	4.10e-03	3.25e-02	11
GO:00726599	Breast	IDC	protein localization to plasma membrane	34/1434	284/18723	6.33e-03	4.47e-02	34

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0501616	Breast	Precancer	Huntington disease	98/684	306/8465	2.85e-35	2.25e-33	1.72e-33	98
hsa0510018	Breast	Precancer	Bacterial invasion of epithelial cells	16/684	77/8465	3.55e-04	2.80e-03	2.15e-03	16
hsa0496110	Breast	Precancer	Endocrine and other factor-regulated calcium reabsorption	11/684	53/8465	2.92e-03	1.81e-02	1.39e-02	11
hsa0501617	Breast	Precancer	Huntington disease	98/684	306/8465	2.85e-35	2.25e-33	1.72e-33	98
hsa0510019	Breast	Precancer	Bacterial invasion of epithelial cells	16/684	77/8465	3.55e-04	2.80e-03	2.15e-03	16
hsa0496111	Breast	Precancer	Endocrine and other factor-regulated calcium reabsorption	11/684	53/8465	2.92e-03	1.81e-02	1.39e-02	11
hsa0501623	Breast	IDC	Huntington disease	103/867	306/8465	5.14e-30	4.17e-28	3.12e-28	103
hsa0510024	Breast	IDC	Bacterial invasion of epithelial cells	17/867	77/8465	1.69e-03	1.19e-02	8.93e-03	17
hsa0496121	Breast	IDC	Endocrine and other factor-regulated calcium reabsorption	12/867	53/8465	6.29e-03	3.30e-02	2.47e-02	12
hsa0501633	Breast	IDC	Huntington disease	103/867	306/8465	5.14e-30	4.17e-28	3.12e-28	103
hsa0510034	Breast	IDC	Bacterial invasion of epithelial cells	17/867	77/8465	1.69e-03	1.19e-02	8.93e-03	17
hsa0496131	Breast	IDC	Endocrine and other factor-regulated calcium reabsorption	12/867	53/8465	6.29e-03	3.30e-02	2.47e-02	12
hsa0501643	Breast	DCIS	Huntington disease	101/846	306/8465	1.54e-29	1.24e-27	9.13e-28	101
hsa0510042	Breast	DCIS	Bacterial invasion of epithelial cells	16/846	77/8465	3.41e-03	1.98e-02	1.46e-02	16
hsa0496141	Breast	DCIS	Endocrine and other factor-regulated calcium reabsorption	12/846	53/8465	5.17e-03	2.69e-02	1.98e-02	12
hsa0414416	Breast	DCIS	Endocytosis	37/846	251/8465	9.92e-03	4.40e-02	3.24e-02	37
hsa0501653	Breast	DCIS	Huntington disease	101/846	306/8465	1.54e-29	1.24e-27	9.13e-28	101
hsa0510052	Breast	DCIS	Bacterial invasion of epithelial cells	16/846	77/8465	3.41e-03	1.98e-02	1.46e-02	16
hsa0496151	Breast	DCIS	Endocrine and other factor-regulated calcium reabsorption	12/846	53/8465	5.17e-03	2.69e-02	1.98e-02	12
hsa0414417	Breast	DCIS	Endocytosis	37/846	251/8465	9.92e-03	4.40e-02	3.24e-02	37

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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

CLTC

SNV

Missense_Mutation

novel

c.4405N>A

p.Glu1469Lys

p.E1469K

protein_coding

deleterious(0.02)

possibly_damaging(0.72)

TCGA-3C-AALI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Poly E

Complete Response

CLTC

SNV

Missense_Mutation

novel

c.1978N>T

p.Gly660Cys

p.G660C

protein_coding

deleterious(0)

benign(0.307)

TCGA-A2-A25A-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Cytoxan

CLTC

SNV

Missense_Mutation

c.4126N>C

p.Asp1376His

p.D1376H

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CLTC

SNV

Missense_Mutation

c.3052N>C

p.Asp1018His

p.D1018H

protein_coding

tolerated(0.3)

possibly_damaging(0.771)

TCGA-AN-A0XW-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

CLTC

SNV

Missense_Mutation

c.3622N>A

p.Arg1208Ser

p.R1208S

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AR-A1AO-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

CLTC

SNV

Missense_Mutation

novel

c.1195N>A

p.Pro399Thr

p.P399T

protein_coding

tolerated(0.06)

benign(0.023)

TCGA-BH-A0BZ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

CLTC

SNV

Missense_Mutation

c.22C>T

p.Arg8Cys

p.R8C

protein_coding

deleterious(0.01)

probably_damaging(0.944)

TCGA-C8-A274-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

CLTC

SNV

Missense_Mutation

novel

c.4462N>G

p.Ile1488Val

p.I1488V

protein_coding

tolerated(0.49)

benign(0.045)

TCGA-E9-A5UP-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

CLTC

SNV

Missense_Mutation

c.658N>C

p.Phe220Leu

p.F220L

protein_coding

tolerated(0.13)

probably_damaging(0.995)

TCGA-GM-A2DN-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxol

CLTC

insertion

In_Frame_Ins

novel

c.2282_2283insTGCTCAACTGTGTGAAAAGGCTGGCCTACT

p.Glu761delinsAspAlaGlnLeuCysGluLysAlaGlyLeuLeu

p.E761delinsDAQLCEKAGLL

protein_coding

TCGA-AO-A0J9-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

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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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