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: RALY

Gene summary for RALY

Gene summary.

Gene information	Species	Human
	Gene symbol	RALY
	Gene ID	22913
	Gene name	RALY heterogeneous nuclear ribonucleoprotein
	Gene Alias	HNRPCL2
	Cytomap	20q11.22
	Gene Type	protein-coding
	GO ID	GO:0000375
	UniProtAcc	Q9UKM9

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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
22913	RALY	RNA-P17T-P17T-8	Human	Lung	IAC	1.35e-11	6.96e-01	0.3329
22913	RALY	RNA-P25T1-P25T1-1	Human	Lung	AIS	4.10e-02	1.15e-01	-0.2116
22913	RALY	RNA-P6T2-P6T2-2	Human	Lung	IAC	1.03e-07	9.34e-02	-0.0132
22913	RALY	RNA-P6T2-P6T2-3	Human	Lung	IAC	8.90e-13	1.49e-01	-0.013
22913	RALY	RNA-P7T1-P7T1-1	Human	Lung	AIS	3.90e-06	3.67e-01	-0.0961
22913	RALY	RNA-P7T1-P7T1-2	Human	Lung	AIS	6.47e-10	5.21e-01	-0.0876
22913	RALY	RNA-P7T1-P7T1-3	Human	Lung	AIS	4.33e-03	3.00e-01	-0.0822
22913	RALY	RNA-P7T1-P7T1-4	Human	Lung	AIS	8.39e-06	2.50e-01	-0.0809
22913	RALY	C04	Human	Oral cavity	OSCC	1.40e-33	2.54e+00	0.2633
22913	RALY	C21	Human	Oral cavity	OSCC	1.28e-80	2.96e+00	0.2678
22913	RALY	C30	Human	Oral cavity	OSCC	1.62e-55	3.60e+00	0.3055
22913	RALY	C38	Human	Oral cavity	OSCC	1.98e-18	2.21e+00	0.172
22913	RALY	C43	Human	Oral cavity	OSCC	3.79e-90	1.70e+00	0.1704
22913	RALY	C46	Human	Oral cavity	OSCC	8.61e-66	1.62e+00	0.1673
22913	RALY	C51	Human	Oral cavity	OSCC	4.04e-29	1.71e+00	0.2674
22913	RALY	C57	Human	Oral cavity	OSCC	9.76e-70	2.55e+00	0.1679
22913	RALY	C06	Human	Oral cavity	OSCC	9.87e-12	2.15e+00	0.2699
22913	RALY	C07	Human	Oral cavity	OSCC	7.73e-08	1.71e+00	0.2491
22913	RALY	C08	Human	Oral cavity	OSCC	3.91e-75	1.54e+00	0.1919
22913	RALY	C09	Human	Oral cavity	OSCC	5.33e-10	5.93e-01	0.1431

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Colorectum (GSE201348)		FAP: Familial adenomatous polyposis
		CRC: Colorectal cancer
Colorectum (HTA11)		AD: Adenomas
		SER: Sessile serrated lesions
		MSI-H: Microsatellite-high colorectal cancer
		MSS: Microsatellite stable colorectal cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ
Thyroid		ATC: Anaplastic thyroid cancer
		HT: Hashimoto's thyroiditis
		PTC: Papillary thyroid cancer

∗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:0008380	Colorectum	AD	RNA splicing	169/3918	434/18723	3.59e-18	2.04e-15	169
GO:0000377	Colorectum	AD	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	130/3918	320/18723	5.88e-16	2.16e-13	130
GO:0000398	Colorectum	AD	mRNA splicing, via spliceosome	130/3918	320/18723	5.88e-16	2.16e-13	130
GO:0000375	Colorectum	AD	RNA splicing, via transesterification reactions	131/3918	324/18723	7.11e-16	2.22e-13	131
GO:00083801	Colorectum	SER	RNA splicing	123/2897	434/18723	3.84e-12	8.41e-10	123
GO:00003751	Colorectum	SER	RNA splicing, via transesterification reactions	90/2897	324/18723	8.68e-09	7.50e-07	90
GO:00003771	Colorectum	SER	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	89/2897	320/18723	9.82e-09	8.14e-07	89
GO:00003981	Colorectum	SER	mRNA splicing, via spliceosome	89/2897	320/18723	9.82e-09	8.14e-07	89
GO:00083802	Colorectum	MSS	RNA splicing	159/3467	434/18723	1.75e-19	1.22e-16	159
GO:00003772	Colorectum	MSS	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	121/3467	320/18723	2.52e-16	8.27e-14	121
GO:00003982	Colorectum	MSS	mRNA splicing, via spliceosome	121/3467	320/18723	2.52e-16	8.27e-14	121
GO:00003752	Colorectum	MSS	RNA splicing, via transesterification reactions	122/3467	324/18723	2.75e-16	8.58e-14	122
GO:00083804	Colorectum	FAP	RNA splicing	108/2622	434/18723	7.90e-10	1.86e-07	108
GO:00003754	Colorectum	FAP	RNA splicing, via transesterification reactions	84/2622	324/18723	8.06e-09	1.10e-06	84
GO:00003774	Colorectum	FAP	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	83/2622	320/18723	9.66e-09	1.23e-06	83
GO:00003984	Colorectum	FAP	mRNA splicing, via spliceosome	83/2622	320/18723	9.66e-09	1.23e-06	83
GO:00083805	Colorectum	CRC	RNA splicing	90/2078	434/18723	2.80e-09	7.97e-07	90
GO:00003775	Colorectum	CRC	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	66/2078	320/18723	4.39e-07	3.37e-05	66
GO:00003985	Colorectum	CRC	mRNA splicing, via spliceosome	66/2078	320/18723	4.39e-07	3.37e-05	66
GO:00003755	Colorectum	CRC	RNA splicing, via transesterification reactions	66/2078	324/18723	7.00e-07	4.61e-05	66

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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

RALY

SNV

Missense_Mutation

novel

c.898N>T

p.Ala300Ser

p.A300S

Q9UKM9

protein_coding

deleterious_low_confidence(0.03)

benign(0.285)

TCGA-A2-A25A-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Cytoxan

RALY

SNV

Missense_Mutation

rs768865097

c.364N>A

p.Asp122Asn

p.D122N

Q9UKM9

protein_coding

tolerated(0.08)

possibly_damaging(0.494)

TCGA-AQ-A0Y5-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

cytoxan

RALY

SNV

Missense_Mutation

c.406N>A

p.Pro136Thr

p.P136T

Q9UKM9

protein_coding

deleterious(0)

possibly_damaging(0.714)

TCGA-BH-A0BZ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

RALY

SNV

Missense_Mutation

c.169T>C

p.Tyr57His

p.Y57H

Q9UKM9

protein_coding

deleterious(0.02)

possibly_damaging(0.739)

TCGA-D8-A1XQ-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

RALY

SNV

Missense_Mutation

novel

c.205N>T

p.Arg69Trp

p.R69W

Q9UKM9

protein_coding

deleterious(0.05)

benign(0.362)

TCGA-LL-A73Y-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

taxotere

RALY

SNV

Missense_Mutation

novel

c.185A>G

p.Tyr62Cys

p.Y62C

Q9UKM9

protein_coding

deleterious(0.04)

benign(0.434)

TCGA-LL-A740-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

RALY

SNV

Missense_Mutation

c.271N>A

p.Gly91Arg

p.G91R

Q9UKM9

protein_coding

deleterious(0)

probably_damaging(0.995)

TCGA-EK-A2PG-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

RALY

SNV

Missense_Mutation

c.67G>C

p.Val23Leu

p.V23L

Q9UKM9

protein_coding

deleterious(0.01)

probably_damaging(0.997)

TCGA-LP-A4AW-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

RALY

SNV

Missense_Mutation

novel

c.233N>A

p.Arg78Gln

p.R78Q

Q9UKM9

protein_coding

deleterious(0.03)

benign(0.074)

TCGA-AA-3864-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

RALY

SNV

Missense_Mutation

c.104N>C

p.Lys35Thr

p.K35T

Q9UKM9

protein_coding

deleterious(0.01)

probably_damaging(0.999)

TCGA-AA-3977-01

Colorectum

colon adenocarcinoma

Male

>=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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