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: RP1

Gene summary for RP1

Gene summary.

Gene information	Species	Human
	Gene symbol	RP1
	Gene ID	6101
	Gene name	RP1 axonemal microtubule associated
	Gene Alias	DCDC4A
	Cytomap	8q11.23-q12.1
	Gene Type	protein-coding
	GO ID	GO:0000226
	UniProtAcc	P56715

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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
6101	RP1	TD9	Human	Lung	IAC	1.99e-06	1.00e+00	0.088
6101	RP1	RNA-P25T1-P25T1-1	Human	Lung	AIS	1.35e-14	6.37e-01	-0.2116
6101	RP1	RNA-P25T1-P25T1-2	Human	Lung	AIS	1.36e-03	4.77e-01	-0.1941
6101	RP1	RNA-P25T1-P25T1-3	Human	Lung	AIS	4.20e-06	5.18e-01	-0.2107
6101	RP1	RNA-P25T1-P25T1-4	Human	Lung	AIS	1.40e-11	6.14e-01	-0.2119

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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:000725410	Skin	AK	JNK cascade	32/1910	167/18723	3.38e-04	3.42e-03	32
GO:003003826	Skin	AK	contractile actin filament bundle assembly	23/1910	106/18723	3.64e-04	3.59e-03	23
GO:004314926	Skin	AK	stress fiber assembly	23/1910	106/18723	3.64e-04	3.59e-03	23
GO:000717817	Skin	AK	transmembrane receptor protein serine/threonine kinase signaling pathway	57/1910	355/18723	3.69e-04	3.61e-03	57
GO:000268317	Skin	AK	negative regulation of immune system process	67/1910	434/18723	3.74e-04	3.63e-03	67
GO:003166727	Skin	AK	response to nutrient levels	72/1910	474/18723	3.74e-04	3.63e-03	72
GO:00308567	Skin	AK	regulation of epithelial cell differentiation	30/1910	154/18723	3.81e-04	3.67e-03	30
GO:001021210	Skin	AK	response to ionizing radiation	29/1910	148/18723	4.27e-04	4.05e-03	29
GO:00022447	Skin	AK	hematopoietic progenitor cell differentiation	24/1910	114/18723	4.40e-04	4.13e-03	24
GO:20001467	Skin	AK	negative regulation of cell motility	57/1910	359/18723	4.91e-04	4.55e-03	57
GO:007135624	Skin	AK	cellular response to tumor necrosis factor	40/1910	229/18723	4.98e-04	4.58e-03	40
GO:00602186	Skin	AK	hematopoietic stem cell differentiation	10/1910	30/18723	5.26e-04	4.79e-03	10
GO:00720739	Skin	AK	kidney epithelium development	27/1910	136/18723	5.36e-04	4.85e-03	27
GO:003166924	Skin	AK	cellular response to nutrient levels	38/1910	215/18723	5.37e-04	4.86e-03	38
GO:00604857	Skin	AK	mesenchyme development	48/1910	291/18723	5.64e-04	5.06e-03	48
GO:003596726	Skin	AK	cellular response to topologically incorrect protein	24/1910	116/18723	5.74e-04	5.11e-03	24
GO:000165510	Skin	AK	urogenital system development	54/1910	338/18723	5.86e-04	5.20e-03	54
GO:19031318	Skin	AK	mononuclear cell differentiation	65/1910	426/18723	6.24e-04	5.45e-03	65
GO:00443424	Skin	AK	type B pancreatic cell proliferation	8/1910	21/18723	6.95e-04	5.94e-03	8
GO:00456195	Skin	AK	regulation of lymphocyte differentiation	32/1910	174/18723	7.11e-04	6.04e-03	32

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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
SEMA3D	NRP1_PLXNA2	SEMA3D_NRP1_PLXNA2	SEMA3	Breast	ADJ
MDK	LRP1	MDK_LRP1	MK	Breast	DCIS
SEMA4A	NRP1_PLXNA4	SEMA4A_NRP1_PLXNA4	SEMA4	Breast	DCIS
SEMA3C	NRP1_PLXNA4	SEMA3C_NRP1_PLXNA4	SEMA3	Breast	DCIS
SEMA3D	NRP1_PLXNA4	SEMA3D_NRP1_PLXNA4	SEMA3	Breast	DCIS
SEMA3C	NRP1_NRP2	SEMA3C_NRP1_NRP2	SEMA3	Breast	DCIS
MDK	LRP1	MDK_LRP1	MK	Breast	Healthy
SEMA3C	NRP1_PLXNA2	SEMA3C_NRP1_PLXNA2	SEMA3	Breast	Healthy
SEMA3D	NRP1_PLXNA2	SEMA3D_NRP1_PLXNA2	SEMA3	Breast	Healthy
SEMA3C	NRP1_NRP2	SEMA3C_NRP1_NRP2	SEMA3	Breast	Healthy
MDK	LRP1	MDK_LRP1	MK	Breast	IDC
MDK	LRP1	MDK_LRP1	MK	Breast	Precancer
MDK	LRP1	MDK_LRP1	MK	Cervix	ADJ
SEMA3C	NRP1_NRP2	SEMA3C_NRP1_NRP2	SEMA3	Cervix	ADJ
MDK	LRP1	MDK_LRP1	MK	Cervix	CC
SEMA3C	NRP1_PLXNA2	SEMA3C_NRP1_PLXNA2	SEMA3	Cervix	CC
SEMA3C	NRP1_NRP2	SEMA3C_NRP1_NRP2	SEMA3	Cervix	CC
SEMA4A	NRP1_PLXNA2	SEMA4A_NRP1_PLXNA2	SEMA4	Cervix	CC
MDK	LRP1	MDK_LRP1	MK	Cervix	Healthy
MDK	LRP1	MDK_LRP1	MK	Cervix	Precancer

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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

RP1

SNV

Missense_Mutation

novel

c.81G>C

p.Leu27Phe

p.L27F

P56715

protein_coding

tolerated(0.65)

benign(0.007)

TCGA-3C-AALI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Poly E

Complete Response

RP1

SNV

Missense_Mutation

rs747714373

c.2978C>G

p.Ser993Cys

p.S993C

P56715

protein_coding

deleterious(0.02)

possibly_damaging(0.781)

TCGA-5L-AAT0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

RP1

SNV

Missense_Mutation

c.4362C>A

p.Ser1454Arg

p.S1454R

P56715

protein_coding

deleterious(0)

probably_damaging(0.968)

TCGA-A2-A0CW-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

RP1

SNV

Missense_Mutation

novel

c.1138N>T

p.Pro380Ser

p.P380S

protein_coding

deleterious(0.04)

probably_damaging(0.923)

TCGA-A2-A3XV-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

RP1

SNV

Missense_Mutation

novel

c.983N>G

p.Lys328Arg

p.K328R

protein_coding

deleterious(0.01)

probably_damaging(0.994)

TCGA-A7-A4SF-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

RP1

SNV

Missense_Mutation

c.2516N>C

p.Gln839Pro

p.Q839P

P56715

protein_coding

deleterious(0.03)

possibly_damaging(0.641)

TCGA-A8-A06X-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

RP1

SNV

Missense_Mutation

novel

c.4466C>T

p.Ala1489Val

p.A1489V

P56715

protein_coding

tolerated(0.22)

benign(0.01)

TCGA-A8-A092-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

RP1

SNV

Missense_Mutation

c.2675N>T

p.Ala892Val

p.A892V

P56715

protein_coding

tolerated(0.14)

benign(0.039)

TCGA-A8-A09B-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

5-fluorouracil

RP1

SNV

Missense_Mutation

c.1895N>T

p.Ser632Leu

p.S632L

P56715

protein_coding

tolerated(0.2)

benign(0.042)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

RP1

SNV

Missense_Mutation

c.4027N>A

p.Asp1343Asn

p.D1343N

P56715

protein_coding

tolerated(0.07)

benign(0)

TCGA-AN-A041-01

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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