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:004873218	Prostate	BPH	gland development	122/3107	436/18723	1.13e-09	5.01e-08	122
GO:004362018	Prostate	BPH	regulation of DNA-templated transcription in response to stress	28/3107	53/18723	1.57e-09	6.70e-08	28
GO:000756816	Prostate	BPH	aging	100/3107	339/18723	1.77e-09	7.44e-08	100
GO:003629317	Prostate	BPH	response to decreased oxygen levels	96/3107	322/18723	2.03e-09	8.26e-08	96
GO:000166617	Prostate	BPH	response to hypoxia	92/3107	307/18723	3.29e-09	1.27e-07	92
GO:004578518	Prostate	BPH	positive regulation of cell adhesion	120/3107	437/18723	5.22e-09	1.90e-07	120
GO:000170110	Prostate	BPH	in utero embryonic development	104/3107	367/18723	9.17e-09	3.10e-07	104
GO:003410118	Prostate	BPH	erythrocyte homeostasis	48/3107	129/18723	1.34e-08	4.26e-07	48
GO:000226218	Prostate	BPH	myeloid cell homeostasis	54/3107	157/18723	4.02e-08	1.12e-06	54
GO:004361818	Prostate	BPH	regulation of transcription from RNA polymerase II promoter in response to stress	24/3107	47/18723	5.48e-08	1.50e-06	24
GO:003021818	Prostate	BPH	erythrocyte differentiation	44/3107	120/18723	8.72e-08	2.16e-06	44
GO:000189010	Prostate	BPH	placenta development	50/3107	144/18723	8.97e-08	2.20e-06	50
GO:00715597	Prostate	BPH	response to transforming growth factor beta	76/3107	256/18723	1.14e-07	2.73e-06	76
GO:004887218	Prostate	BPH	homeostasis of number of cells	79/3107	272/18723	1.79e-07	3.99e-06	79
GO:003052216	Prostate	BPH	intracellular receptor signaling pathway	77/3107	265/18723	2.49e-07	5.42e-06	77
GO:007145315	Prostate	BPH	cellular response to oxygen levels	56/3107	177/18723	5.50e-07	1.09e-05	56
GO:00075697	Prostate	BPH	cell aging	45/3107	132/18723	7.00e-07	1.35e-05	45
GO:00715607	Prostate	BPH	cellular response to transforming growth factor beta stimulus	72/3107	250/18723	8.71e-07	1.61e-05	72
GO:000189210	Prostate	BPH	embryonic placenta development	32/3107	82/18723	9.93e-07	1.80e-05	32
GO:003629415	Prostate	BPH	cellular response to decreased oxygen levels	51/3107	161/18723	1.66e-06	2.79e-05	51

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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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