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: CITED1

Gene summary for CITED1

Gene summary.

Gene information	Species	Human
	Gene symbol	CITED1
	Gene ID	4435
	Gene name	Cbp/p300 interacting transactivator with Glu/Asp rich carboxy-terminal domain 1
	Gene Alias	MSG1
	Cytomap	Xq13.1
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	Q99966

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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
4435	CITED1	PTC01	Human	Thyroid	PTC	7.73e-39	1.16e+00	0.1899
4435	CITED1	PTC04	Human	Thyroid	PTC	2.47e-31	1.76e+00	0.1927
4435	CITED1	PTC05	Human	Thyroid	PTC	8.87e-36	3.66e+00	0.2065
4435	CITED1	PTC06	Human	Thyroid	PTC	4.46e-49	2.53e+00	0.2057
4435	CITED1	PTC07	Human	Thyroid	PTC	5.36e-55	1.79e+00	0.2044

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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:0006913112	Thyroid	PTC	nucleocytoplasmic transport	181/5968	301/18723	2.93e-24	7.69e-22	181
GO:0051169112	Thyroid	PTC	nuclear transport	181/5968	301/18723	2.93e-24	7.69e-22	181
GO:0016055110	Thyroid	PTC	Wnt signaling pathway	217/5968	444/18723	3.71e-14	2.30e-12	217
GO:0198738110	Thyroid	PTC	cell-cell signaling by wnt	217/5968	446/18723	6.68e-14	3.73e-12	217
GO:0030111110	Thyroid	PTC	regulation of Wnt signaling pathway	163/5968	328/18723	1.05e-11	4.29e-10	163
GO:007155919	Thyroid	PTC	response to transforming growth factor beta	131/5968	256/18723	9.20e-11	3.17e-09	131
GO:0001701111	Thyroid	PTC	in utero embryonic development	175/5968	367/18723	1.40e-10	4.73e-09	175
GO:0070997113	Thyroid	PTC	neuron death	171/5968	361/18723	4.32e-10	1.38e-08	171
GO:007156019	Thyroid	PTC	cellular response to transforming growth factor beta stimulus	126/5968	250/18723	7.34e-10	2.19e-08	126
GO:000717919	Thyroid	PTC	transforming growth factor beta receptor signaling pathway	104/5968	198/18723	1.20e-09	3.47e-08	104
GO:0043434113	Thyroid	PTC	response to peptide hormone	188/5968	414/18723	4.13e-09	1.09e-07	188
GO:1901214113	Thyroid	PTC	regulation of neuron death	151/5968	319/18723	4.74e-09	1.24e-07	151
GO:0051402112	Thyroid	PTC	neuron apoptotic process	118/5968	246/18723	8.99e-08	1.81e-06	118
GO:0032868111	Thyroid	PTC	response to insulin	124/5968	264/18723	1.87e-07	3.47e-06	124
GO:001701515	Thyroid	PTC	regulation of transforming growth factor beta receptor signaling pathway	69/5968	128/18723	1.92e-07	3.51e-06	69
GO:190384415	Thyroid	PTC	regulation of cellular response to transforming growth factor beta stimulus	70/5968	131/18723	2.47e-07	4.31e-06	70
GO:0043523110	Thyroid	PTC	regulation of neuron apoptotic process	102/5968	212/18723	5.45e-07	8.76e-06	102
GO:000182215	Thyroid	PTC	kidney development	133/5968	293/18723	7.57e-07	1.18e-05	133
GO:0001503110	Thyroid	PTC	ossification	176/5968	408/18723	9.26e-07	1.40e-05	176
GO:000717819	Thyroid	PTC	transmembrane receptor protein serine/threonine kinase signaling pathway	156/5968	355/18723	1.02e-06	1.51e-05	156

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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

CITED1

SNV

Missense_Mutation

c.485T>C

p.Leu162Pro

p.L162P

Q99966

protein_coding

tolerated(0.09)

benign(0.347)

TCGA-AN-A0AS-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

CITED1

SNV

Missense_Mutation

rs61732117

c.272N>T

p.Ser91Leu

p.S91L

Q99966

protein_coding

deleterious(0.01)

benign(0.018)

TCGA-D8-A1XK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine+cyclophosphamide

CITED1

SNV

Missense_Mutation

novel

c.404N>T

p.Ala135Val

p.A135V

Q99966

protein_coding

tolerated(0.48)

benign(0.003)

TCGA-EW-A1IZ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

taxotere

CITED1

SNV

Missense_Mutation

novel

c.4G>A

p.Glu2Lys

p.E2K

Q99966

protein_coding

deleterious_low_confidence(0.04)

benign(0.003)

TCGA-UL-AAZ6-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

herceptin

CITED1

SNV

Missense_Mutation

rs773210279

c.527N>T

p.Ser176Leu

p.S176L

Q99966

protein_coding

tolerated(0.15)

benign(0.09)

TCGA-EK-A2RJ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

CITED1

SNV

Missense_Mutation

novel

c.529G>A

p.Asp177Asn

p.D177N

Q99966

protein_coding

deleterious(0)

possibly_damaging(0.856)

TCGA-VS-A9U5-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

CITED1

SNV

Missense_Mutation

c.523N>T

p.Asp175Tyr

p.D175Y

Q99966

protein_coding

deleterious(0)

probably_damaging(0.995)

TCGA-NH-A6GB-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Chemotherapy

oxaliplatin

CITED1

SNV

Missense_Mutation

novel

c.55N>C

p.Ser19Pro

p.S19P

Q99966

protein_coding

deleterious_low_confidence(0.01)

benign(0.003)

TCGA-AJ-A3EL-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

CITED1

SNV

Missense_Mutation

rs751916691

c.182N>T

p.Ala61Val

p.A61V

Q99966

protein_coding

tolerated_low_confidence(0.05)

benign(0.019)

TCGA-AP-A059-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

CITED1

SNV

Missense_Mutation

novel

c.92N>T

p.Ser31Leu

p.S31L

Q99966

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.992)

TCGA-AP-A1DV-01

Endometrium

uterine corpus endometrioid 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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