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:00508072	Prostate	BPH	regulation of synapse organization	48/3107	211/18723	1.23e-02	4.94e-02	48
GO:00071831	Prostate	BPH	SMAD protein complex assembly	6/3107	13/18723	1.24e-02	4.94e-02	6
GO:0033689	Prostate	BPH	negative regulation of osteoblast proliferation	6/3107	13/18723	1.24e-02	4.94e-02	6
GO:00427695	Prostate	BPH	DNA damage response, detection of DNA damage	6/3107	13/18723	1.24e-02	4.94e-02	6
GO:004603419	Prostate	Tumor	ATP metabolic process	122/3246	277/18723	1.71e-25	5.33e-22	122
GO:001603219	Prostate	Tumor	viral process	155/3246	415/18723	7.20e-23	1.12e-19	155
GO:200123319	Prostate	Tumor	regulation of apoptotic signaling pathway	137/3246	356/18723	1.01e-21	1.25e-18	137
GO:000641317	Prostate	Tumor	translational initiation	66/3246	118/18723	2.57e-21	2.66e-18	66
GO:007259417	Prostate	Tumor	establishment of protein localization to organelle	151/3246	422/18723	3.19e-20	2.83e-17	151
GO:000838019	Prostate	Tumor	RNA splicing	153/3246	434/18723	9.15e-20	5.79e-17	153
GO:000641719	Prostate	Tumor	regulation of translation	161/3246	468/18723	1.55e-19	8.74e-17	161
GO:009719319	Prostate	Tumor	intrinsic apoptotic signaling pathway	113/3246	288/18723	6.79e-19	2.64e-16	113
GO:190331117	Prostate	Tumor	regulation of mRNA metabolic process	111/3246	288/18723	6.66e-18	2.30e-15	111
GO:004348419	Prostate	Tumor	regulation of RNA splicing	70/3246	148/18723	3.22e-17	1.05e-14	70
GO:001905819	Prostate	Tumor	viral life cycle	117/3246	317/18723	4.10e-17	1.18e-14	117
GO:000698619	Prostate	Tumor	response to unfolded protein	65/3246	137/18723	3.56e-16	7.50e-14	65
GO:190290319	Prostate	Tumor	regulation of supramolecular fiber organization	131/3246	383/18723	6.68e-16	1.26e-13	131
GO:200124219	Prostate	Tumor	regulation of intrinsic apoptotic signaling pathway	72/3246	164/18723	1.63e-15	2.81e-13	72
GO:003297019	Prostate	Tumor	regulation of actin filament-based process	133/3246	397/18723	2.59e-15	4.35e-13	133
GO:003497619	Prostate	Tumor	response to endoplasmic reticulum stress	97/3246	256/18723	2.92e-15	4.78e-13	97

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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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