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: CIT

Gene summary for CIT

Gene summary.

Gene information	Species	Human
	Gene symbol	CIT
	Gene ID	11113
	Gene name	citron rho-interacting serine/threonine kinase
	Gene Alias	CITK
	Cytomap	12q24.23
	Gene Type	protein-coding
	GO ID	GO:0000278
	UniProtAcc	O14578

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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
11113	CIT	TD9	Human	Lung	IAC	1.02e-02	5.71e-01	0.088
11113	CIT	RNA-P6T1-P6T1-1	Human	Lung	MIAC	6.67e-04	9.05e-01	-0.0238

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma

∗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:009720119	Thyroid	PTC	negative regulation of transcription from RNA polymerase II promoter in response to stress	9/5968	12/18723	2.72e-03	1.36e-02	9
GO:009028712	Thyroid	PTC	regulation of cellular response to growth factor stimulus	120/5968	304/18723	2.87e-03	1.42e-02	120
GO:000176316	Thyroid	PTC	morphogenesis of a branching structure	81/5968	196/18723	3.20e-03	1.57e-02	81
GO:00720067	Thyroid	PTC	nephron development	61/5968	142/18723	3.49e-03	1.69e-02	61
GO:00485388	Thyroid	PTC	thymus development	23/5968	45/18723	5.62e-03	2.55e-02	23
GO:004654612	Thyroid	PTC	development of primary male sexual characteristics	60/5968	142/18723	5.79e-03	2.61e-02	60
GO:004863810	Thyroid	PTC	regulation of developmental growth	127/5968	330/18723	6.09e-03	2.71e-02	127
GO:006141812	Thyroid	PTC	regulation of transcription from RNA polymerase II promoter in response to hypoxia	9/5968	13/18723	6.33e-03	2.79e-02	9
GO:00705558	Thyroid	PTC	response to interleukin-1	60/5968	143/18723	6.93e-03	2.98e-02	60
GO:007216313	Thyroid	PTC	mesonephric epithelium development	41/5968	92/18723	7.12e-03	3.06e-02	41
GO:007216413	Thyroid	PTC	mesonephric tubule development	41/5968	92/18723	7.12e-03	3.06e-02	41
GO:00611387	Thyroid	PTC	morphogenesis of a branching epithelium	74/5968	182/18723	7.45e-03	3.18e-02	74
GO:000858412	Thyroid	PTC	male gonad development	59/5968	141/18723	7.88e-03	3.33e-02	59
GO:003434110	Thyroid	PTC	response to interferon-gamma	59/5968	141/18723	7.88e-03	3.33e-02	59
GO:000157011	Thyroid	PTC	vasculogenesis	36/5968	80/18723	9.35e-03	3.85e-02	36
GO:006048514	Thyroid	PTC	mesenchyme development	112/5968	291/18723	9.48e-03	3.90e-02	112
GO:000182313	Thyroid	PTC	mesonephros development	42/5968	96/18723	9.53e-03	3.91e-02	42
GO:000165713	Thyroid	PTC	ureteric bud development	40/5968	91/18723	1.02e-02	4.14e-02	40
GO:00610056	Thyroid	PTC	cell differentiation involved in kidney development	27/5968	57/18723	1.04e-02	4.18e-02	27
GO:001470617	Thyroid	PTC	striated muscle tissue development	144/5968	384/18723	1.05e-02	4.22e-02	144

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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

CIT

SNV

Missense_Mutation

rs779515686

c.4130N>T

p.Pro1377Leu

p.P1377L

O14578

protein_coding

deleterious(0)

benign(0.248)

TCGA-A2-A0EW-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

CIT

SNV

Missense_Mutation

c.5132C>T

p.Ser1711Phe

p.S1711F

O14578

protein_coding

deleterious(0)

probably_damaging(0.972)

TCGA-A2-A0SV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Other, specify in notesBisphosphonate therapy

zometa

CIT

SNV

Missense_Mutation

novel

c.2482N>A

p.Glu828Lys

p.E828K

O14578

protein_coding

deleterious(0.04)

possibly_damaging(0.628)

TCGA-A2-A25C-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

CIT

SNV

Missense_Mutation

c.3097G>T

p.Val1033Leu

p.V1033L

O14578

protein_coding

tolerated(0.08)

probably_damaging(0.978)

TCGA-A8-A076-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

CIT

SNV

Missense_Mutation

rs747447396

c.2839C>T

p.Arg947Cys

p.R947C

O14578

protein_coding

deleterious(0.02)

possibly_damaging(0.446)

TCGA-A8-A09X-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

CIT

SNV

Missense_Mutation

rs747447396

c.2839N>T

p.Arg947Cys

p.R947C

O14578

protein_coding

deleterious(0.02)

possibly_damaging(0.446)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CIT

SNV

Missense_Mutation

c.242N>T

p.Ser81Phe

p.S81F

O14578

protein_coding

deleterious(0.02)

benign(0.17)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CIT

SNV

Missense_Mutation

novel

c.637N>T

p.His213Tyr

p.H213Y

O14578

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AC-A5XS-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

femara

CIT

SNV

Missense_Mutation

rs368981957

c.5590N>A

p.Asp1864Asn

p.D1864N

O14578

protein_coding

deleterious(0)

probably_damaging(0.964)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CIT

SNV

Missense_Mutation

novel

c.1771N>A

p.Glu591Lys

p.E591K

O14578

protein_coding

tolerated(0.31)

benign(0.019)

TCGA-AN-A046-01

Breast

breast invasive 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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