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:0007369	Colorectum	AD	gastrulation	53/3918	185/18723	7.60e-03	4.60e-02	53
GO:0031623	Colorectum	AD	receptor internalization	35/3918	113/18723	7.72e-03	4.66e-02	35
GO:0043524	Colorectum	AD	negative regulation of neuron apoptotic process	43/3918	145/18723	8.04e-03	4.73e-02	43
GO:0043502	Colorectum	AD	regulation of muscle adaptation	31/3918	98/18723	8.45e-03	4.94e-02	31
GO:00460341	Colorectum	SER	ATP metabolic process	117/2897	277/18723	5.54e-27	1.13e-23	117
GO:00421761	Colorectum	SER	regulation of protein catabolic process	126/2897	391/18723	5.33e-17	2.52e-14	126
GO:19033621	Colorectum	SER	regulation of cellular protein catabolic process	91/2897	255/18723	1.22e-15	5.36e-13	91
GO:00325351	Colorectum	SER	regulation of cellular component size	115/2897	383/18723	3.04e-13	1.10e-10	115
GO:00726591	Colorectum	SER	protein localization to plasma membrane	92/2897	284/18723	6.36e-13	1.86e-10	92
GO:00083801	Colorectum	SER	RNA splicing	123/2897	434/18723	3.84e-12	8.41e-10	123
GO:00329701	Colorectum	SER	regulation of actin filament-based process	115/2897	397/18723	4.16e-12	8.80e-10	115
GO:00457321	Colorectum	SER	positive regulation of protein catabolic process	77/2897	231/18723	9.91e-12	1.90e-09	77
GO:00432541	Colorectum	SER	regulation of protein-containing complex assembly	119/2897	428/18723	3.34e-11	5.86e-09	119
GO:19038291	Colorectum	SER	positive regulation of cellular protein localization	86/2897	276/18723	3.61e-11	6.11e-09	86
GO:00329561	Colorectum	SER	regulation of actin cytoskeleton organization	104/2897	358/18723	3.68e-11	6.11e-09	104
GO:00098961	Colorectum	SER	positive regulation of catabolic process	132/2897	492/18723	4.16e-11	6.72e-09	132
GO:19907781	Colorectum	SER	protein localization to cell periphery	98/2897	333/18723	6.09e-11	9.57e-09	98
GO:20012421	Colorectum	SER	regulation of intrinsic apoptotic signaling pathway	59/2897	164/18723	8.42e-11	1.20e-08	59
GO:00971931	Colorectum	SER	intrinsic apoptotic signaling pathway	87/2897	288/18723	1.67e-10	2.32e-08	87
GO:19033641	Colorectum	SER	positive regulation of cellular protein catabolic process	56/2897	155/18723	2.09e-10	2.85e-08	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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