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:003295628	Skin	AK	regulation of actin cytoskeleton organization	66/1910	358/18723	1.40e-06	4.26e-05	66
GO:007147810	Skin	AK	cellular response to radiation	41/1910	186/18723	1.53e-06	4.61e-05	41
GO:01501179	Skin	AK	positive regulation of cell-substrate junction organization	14/1910	33/18723	1.58e-06	4.73e-05	14
GO:009026317	Skin	AK	positive regulation of canonical Wnt signaling pathway	28/1910	106/18723	1.73e-06	5.13e-05	28
GO:000756826	Skin	AK	aging	63/1910	339/18723	1.83e-06	5.42e-05	63
GO:190495126	Skin	AK	positive regulation of establishment of protein localization	60/1910	319/18723	2.14e-06	6.12e-05	60
GO:000155820	Skin	AK	regulation of cell growth	73/1910	414/18723	2.21e-06	6.27e-05	73
GO:007156010	Skin	AK	cellular response to transforming growth factor beta stimulus	50/1910	250/18723	2.45e-06	6.76e-05	50
GO:005101728	Skin	AK	actin filament bundle assembly	36/1910	157/18723	2.48e-06	6.76e-05	36
GO:190188815	Skin	AK	regulation of cell junction assembly	43/1910	204/18723	2.99e-06	7.93e-05	43
GO:000931420	Skin	AK	response to radiation	78/1910	456/18723	3.32e-06	8.59e-05	78
GO:005140319	Skin	AK	stress-activated MAPK cascade	48/1910	239/18723	3.43e-06	8.82e-05	48
GO:003287218	Skin	AK	regulation of stress-activated MAPK cascade	41/1910	192/18723	3.57e-06	8.96e-05	41
GO:006056016	Skin	AK	developmental growth involved in morphogenesis	47/1910	234/18723	4.30e-06	1.05e-04	47
GO:006157228	Skin	AK	actin filament bundle organization	36/1910	161/18723	4.59e-06	1.10e-04	36
GO:007030218	Skin	AK	regulation of stress-activated protein kinase signaling cascade	41/1910	195/18723	5.36e-06	1.24e-04	41
GO:011005328	Skin	AK	regulation of actin filament organization	53/1910	278/18723	5.48e-06	1.26e-04	53
GO:190370625	Skin	AK	regulation of hemopoiesis	65/1910	367/18723	6.74e-06	1.52e-04	65
GO:00518949	Skin	AK	positive regulation of focal adhesion assembly	12/1910	28/18723	7.83e-06	1.72e-04	12
GO:005122226	Skin	AK	positive regulation of protein transport	56/1910	303/18723	7.96e-06	1.74e-04	56

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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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