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: TG

Gene summary for TG

Gene summary.

Gene information	Species	Human
	Gene symbol	TG
	Gene ID	7038
	Gene name	thyroglobulin
	Gene Alias	AITD3
	Cytomap	8q24.22
	Gene Type	protein-coding
	GO ID	GO:0006575
	UniProtAcc	P01266

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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
7038	TG	Adj_PTCwithHT_6	Human	Thyroid	HT	7.30e-105	-2.11e+00	0.02
7038	TG	Adj_PTCwithHT_8	Human	Thyroid	HT	6.03e-06	-2.18e-01	0.0267
7038	TG	PTCwithHT_1	Human	Thyroid	HT	1.56e-31	-1.52e+00	0.0238
7038	TG	PTCwithHT_6	Human	Thyroid	HT	1.38e-104	-2.12e+00	0.02
7038	TG	PTCwithHT_8	Human	Thyroid	HT	2.54e-58	-1.07e+00	0.0351
7038	TG	PTCwithoutHT_2	Human	Thyroid	PTC	3.80e-11	-3.56e-01	0.0419
7038	TG	PTCwithoutHT_7	Human	Thyroid	PTC	4.95e-19	-8.43e-01	0.0381
7038	TG	male-WTA	Human	Thyroid	PTC	1.56e-05	1.85e-01	0.1037
7038	TG	nodule-WTA	Human	Thyroid	goiters	1.11e-15	2.90e-01	0.0534
7038	TG	PTC01	Human	Thyroid	PTC	1.01e-25	2.49e+00	0.1899
7038	TG	PTC03	Human	Thyroid	PTC	2.57e-11	1.84e+00	0.1784
7038	TG	PTC04	Human	Thyroid	PTC	7.44e-08	1.70e+00	0.1927
7038	TG	PTC05	Human	Thyroid	PTC	7.32e-32	2.88e+00	0.2065
7038	TG	PTC06	Human	Thyroid	PTC	8.06e-54	4.16e+00	0.2057
7038	TG	PTC07	Human	Thyroid	PTC	5.54e-48	2.79e+00	0.2044
7038	TG	ATC08	Human	Thyroid	ATC	1.04e-55	-1.49e+00	0.0541
7038	TG	ATC09	Human	Thyroid	ATC	2.30e-54	-2.31e+00	0.2871
7038	TG	ATC11	Human	Thyroid	ATC	5.27e-20	-2.31e+00	0.3386
7038	TG	ATC12	Human	Thyroid	ATC	2.29e-129	-2.31e+00	0.34
7038	TG	ATC13	Human	Thyroid	ATC	7.68e-130	-2.30e+00	0.34

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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:00060918	Breast	Precancer	generation of precursor metabolites and energy	94/1080	490/18723	1.54e-25	1.64e-22	94
GO:00159808	Breast	Precancer	energy derivation by oxidation of organic compounds	70/1080	318/18723	8.33e-23	6.37e-20	70
GO:00226139	Breast	Precancer	ribonucleoprotein complex biogenesis	79/1080	463/18723	2.11e-18	1.03e-15	79
GO:00718269	Breast	Precancer	ribonucleoprotein complex subunit organization	48/1080	227/18723	2.68e-15	8.45e-13	48
GO:00226189	Breast	Precancer	ribonucleoprotein complex assembly	47/1080	220/18723	3.47e-15	1.03e-12	47
GO:00069799	Breast	Precancer	response to oxidative stress	70/1080	446/18723	1.59e-14	4.26e-12	70
GO:00064578	Breast	Precancer	protein folding	43/1080	212/18723	3.48e-13	7.45e-11	43
GO:00064179	Breast	Precancer	regulation of translation	67/1080	468/18723	4.71e-12	7.64e-10	67
GO:00485459	Breast	Precancer	response to steroid hormone	53/1080	339/18723	3.07e-11	3.66e-09	53
GO:00160329	Breast	Precancer	viral process	58/1080	415/18723	3.42e-10	3.16e-08	58
GO:00064588	Breast	Precancer	'de novo' protein folding	16/1080	43/18723	8.14e-10	6.92e-08	16
GO:00190589	Breast	Precancer	viral life cycle	47/1080	317/18723	2.42e-09	1.99e-07	47
GO:00610778	Breast	Precancer	chaperone-mediated protein folding	19/1080	67/18723	4.22e-09	3.28e-07	19
GO:00709979	Breast	Precancer	neuron death	50/1080	361/18723	7.75e-09	5.70e-07	50
GO:00510848	Breast	Precancer	'de novo' posttranslational protein folding	14/1080	39/18723	1.61e-08	1.12e-06	14
GO:00510858	Breast	Precancer	chaperone cofactor-dependent protein refolding	13/1080	34/18723	2.17e-08	1.47e-06	13
GO:00514029	Breast	Precancer	neuron apoptotic process	38/1080	246/18723	2.68e-08	1.75e-06	38
GO:00444039	Breast	Precancer	biological process involved in symbiotic interaction	42/1080	290/18723	3.40e-08	2.11e-06	42
GO:00521269	Breast	Precancer	movement in host environment	29/1080	175/18723	2.59e-07	1.28e-05	29
GO:00509006	Breast	Precancer	leukocyte migration	47/1080	369/18723	2.82e-07	1.39e-05	47

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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
COL1A1	ITGA1_ITGB1	COL1A1_ITGA1_ITGB1	COLLAGEN	Breast	ADJ
COL1A2	ITGA1_ITGB1	COL1A2_ITGA1_ITGB1	COLLAGEN	Breast	ADJ
COL4A1	ITGA1_ITGB1	COL4A1_ITGA1_ITGB1	COLLAGEN	Breast	ADJ
COL4A2	ITGA1_ITGB1	COL4A2_ITGA1_ITGB1	COLLAGEN	Breast	ADJ
COL6A1	ITGA1_ITGB1	COL6A1_ITGA1_ITGB1	COLLAGEN	Breast	ADJ
COL6A2	ITGA1_ITGB1	COL6A2_ITGA1_ITGB1	COLLAGEN	Breast	ADJ
COL6A3	ITGA1_ITGB1	COL6A3_ITGA1_ITGB1	COLLAGEN	Breast	ADJ
COL1A1	ITGA2_ITGB1	COL1A1_ITGA2_ITGB1	COLLAGEN	Breast	ADJ
COL1A2	ITGA2_ITGB1	COL1A2_ITGA2_ITGB1	COLLAGEN	Breast	ADJ
COL4A1	ITGA2_ITGB1	COL4A1_ITGA2_ITGB1	COLLAGEN	Breast	ADJ
COL4A2	ITGA2_ITGB1	COL4A2_ITGA2_ITGB1	COLLAGEN	Breast	ADJ
COL6A1	ITGA2_ITGB1	COL6A1_ITGA2_ITGB1	COLLAGEN	Breast	ADJ
COL6A2	ITGA2_ITGB1	COL6A2_ITGA2_ITGB1	COLLAGEN	Breast	ADJ
COL6A3	ITGA2_ITGB1	COL6A3_ITGA2_ITGB1	COLLAGEN	Breast	ADJ
LAMA2	ITGA1_ITGB1	LAMA2_ITGA1_ITGB1	LAMININ	Breast	ADJ
LAMA4	ITGA1_ITGB1	LAMA4_ITGA1_ITGB1	LAMININ	Breast	ADJ
LAMB2	ITGA1_ITGB1	LAMB2_ITGA1_ITGB1	LAMININ	Breast	ADJ
LAMB3	ITGA1_ITGB1	LAMB3_ITGA1_ITGB1	LAMININ	Breast	ADJ
LAMC1	ITGA1_ITGB1	LAMC1_ITGA1_ITGB1	LAMININ	Breast	ADJ
LAMC2	ITGA1_ITGB1	LAMC2_ITGA1_ITGB1	LAMININ	Breast	ADJ

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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

SNV

Missense_Mutation

rs201480815

c.3416N>T

p.Ser1139Leu

p.S1139L

P01266

protein_coding

tolerated(0.14)

benign(0)

TCGA-A1-A0SK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SNV

Missense_Mutation

c.4662G>T

p.Trp1554Cys

p.W1554C

P01266

protein_coding

deleterious(0.01)

benign(0.123)

TCGA-A1-A0SP-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

SNV

Missense_Mutation

c.4882N>T

p.Asp1628Tyr

p.D1628Y

P01266

protein_coding

deleterious(0)

possibly_damaging(0.861)

TCGA-A2-A04W-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

SNV

Missense_Mutation

c.3133N>A

p.Gly1045Arg

p.G1045R

P01266

protein_coding

tolerated(0.13)

benign(0.007)

TCGA-A2-A25B-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

SNV

Missense_Mutation

c.5223N>C

p.Gln1741His

p.Q1741H

P01266

protein_coding

deleterious(0.02)

probably_damaging(0.994)

TCGA-A2-A25B-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

SNV

Missense_Mutation

rs773795717

c.4645C>T

p.Arg1549Trp

p.R1549W

P01266

protein_coding

deleterious(0.05)

benign(0.232)

TCGA-A7-A13E-01

Breast

breast invasive carcinoma

Female

<65

I/II

Targeted Molecular therapy

bevacizumab

SNV

Missense_Mutation

novel

c.1093N>A

p.Ala365Thr

p.A365T

P01266

protein_coding

tolerated(0.44)

benign(0)

TCGA-A7-A26I-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cytoxan

SNV

Missense_Mutation

rs146594373

c.4268N>A

p.Arg1423His

p.R1423H

P01266

protein_coding

tolerated(0.55)

benign(0.001)

TCGA-A8-A06O-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

letrozole

SNV

Missense_Mutation

c.746G>A

p.Gly249Asp

p.G249D

P01266

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-A8-A07L-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

SNV

Missense_Mutation

c.3746N>T

p.Cys1249Phe

p.C1249F

P01266

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-A8-A08F-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

5-fluorouracil

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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
7038	TG	DRUGGABLE GENOME, HORMONE ACTIVITY		RETINOIDS		12182039
7038	TG	DRUGGABLE GENOME, HORMONE ACTIVITY		FDG	FLUDEOXYGLUCOSE-F18	10452315
7038	TG	DRUGGABLE GENOME, HORMONE ACTIVITY		BISPECIFIC ANTIBODY		10433080
7038	TG	DRUGGABLE GENOME, HORMONE ACTIVITY		PHENYTOIN	PHENYTOIN	3935423
7038	TG	DRUGGABLE GENOME, HORMONE ACTIVITY		PREDNISONE	PREDNISONE	2745931
7038	TG	DRUGGABLE GENOME, HORMONE ACTIVITY		ALL-TRANS-RETINOIC ACID		10946899
7038	TG	DRUGGABLE GENOME, HORMONE ACTIVITY		TGFBETA1		10770487,10194419
7038	TG	DRUGGABLE GENOME, HORMONE ACTIVITY		RETINOIC ACID		11563543
7038	TG	DRUGGABLE GENOME, HORMONE ACTIVITY		PREDNISOLONE	PREDNISOLONE	3427792,8636270
7038	TG	DRUGGABLE GENOME, HORMONE ACTIVITY		AMIODARONE	AMIODARONE	8778159

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