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: FBL

Gene summary for FBL

Gene summary.

Gene information	Species	Human
	Gene symbol	FBL
	Gene ID	2091
	Gene name	fibrillarin
	Gene Alias	FIB
	Cytomap	19q13.2
	Gene Type	protein-coding
	GO ID	GO:0000154
	UniProtAcc	P22087

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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
2091	FBL	GSM4909285	Human	Breast	IDC	1.42e-28	6.19e-01	0.21
2091	FBL	GSM4909286	Human	Breast	IDC	3.90e-29	5.57e-01	0.1081
2091	FBL	GSM4909294	Human	Breast	IDC	5.93e-04	-2.37e-01	0.2022
2091	FBL	GSM4909296	Human	Breast	IDC	5.16e-08	-1.82e-02	0.1524
2091	FBL	GSM4909297	Human	Breast	IDC	1.90e-13	-3.35e-01	0.1517
2091	FBL	GSM4909311	Human	Breast	IDC	2.45e-34	-2.29e-01	0.1534
2091	FBL	GSM4909312	Human	Breast	IDC	4.97e-10	-1.24e-02	0.1552
2091	FBL	GSM4909319	Human	Breast	IDC	5.59e-33	-3.80e-01	0.1563
2091	FBL	GSM4909320	Human	Breast	IDC	2.12e-04	-2.10e-01	0.1575
2091	FBL	GSM4909321	Human	Breast	IDC	5.24e-12	-1.69e-01	0.1559
2091	FBL	brca3	Human	Breast	Precancer	2.80e-02	5.33e-02	-0.0263
2091	FBL	NCCBC14	Human	Breast	DCIS	3.24e-11	-3.32e-01	0.2021
2091	FBL	NCCBC3	Human	Breast	DCIS	2.67e-02	-9.59e-02	0.1198
2091	FBL	NCCBC5	Human	Breast	DCIS	4.86e-10	-2.11e-01	0.2046
2091	FBL	P1	Human	Breast	IDC	9.52e-20	-4.29e-01	0.1527
2091	FBL	DCIS2	Human	Breast	DCIS	5.31e-50	9.70e-05	0.0085
2091	FBL	HTA11_3410_2000001011	Human	Colorectum	AD	1.57e-56	9.71e-01	0.0155
2091	FBL	HTA11_2487_2000001011	Human	Colorectum	SER	1.73e-21	7.91e-01	-0.1808
2091	FBL	HTA11_2951_2000001011	Human	Colorectum	AD	6.92e-17	1.15e+00	0.0216
2091	FBL	HTA11_1938_2000001011	Human	Colorectum	AD	7.77e-30	8.98e-01	-0.0811

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid 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
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
Prostate		BPH: Benign Prostatic Hyperplasia
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:003158922	Liver	HCC	cell-substrate adhesion	188/7958	363/18723	2.00e-04	1.55e-03	188
GO:00075962	Liver	HCC	blood coagulation	118/7958	217/18723	2.63e-04	1.94e-03	118
GO:00075992	Liver	HCC	hemostasis	119/7958	222/18723	5.25e-04	3.41e-03	119
GO:00434097	Liver	HCC	negative regulation of MAPK cascade	98/7958	180/18723	7.88e-04	4.74e-03	98
GO:00508172	Liver	HCC	coagulation	118/7958	222/18723	8.41e-04	5.03e-03	118
GO:005087822	Liver	HCC	regulation of body fluid levels	191/7958	379/18723	1.06e-03	6.11e-03	191
GO:00723762	Liver	HCC	protein activation cascade	10/7958	12/18723	4.79e-03	2.02e-02	10
GO:00107711	Liver	HCC	negative regulation of cell morphogenesis involved in differentiation	11/7958	14/18723	6.81e-03	2.73e-02	11
GO:19000251	Liver	HCC	negative regulation of substrate adhesion-dependent cell spreading	11/7958	14/18723	6.81e-03	2.73e-02	11
GO:00075651	Liver	HCC	female pregnancy	99/7958	193/18723	8.24e-03	3.23e-02	99
GO:000164911	Liver	HCC	osteoblast differentiation	115/7958	229/18723	1.08e-02	3.99e-02	115
GO:002261320	Oral cavity	OSCC	ribonucleoprotein complex biogenesis	333/7305	463/18723	8.28e-48	5.24e-44	333
GO:004225420	Oral cavity	OSCC	ribosome biogenesis	230/7305	299/18723	3.22e-41	6.80e-38	230
GO:000636410	Oral cavity	OSCC	rRNA processing	172/7305	225/18723	1.57e-30	1.24e-27	172
GO:00344709	Oral cavity	OSCC	ncRNA processing	263/7305	395/18723	4.38e-29	2.78e-26	263
GO:001607210	Oral cavity	OSCC	rRNA metabolic process	176/7305	236/18723	6.51e-29	3.24e-26	176
GO:000640318	Oral cavity	OSCC	RNA localization	150/7305	201/18723	6.90e-25	1.98e-22	150
GO:00346605	Oral cavity	OSCC	ncRNA metabolic process	296/7305	485/18723	2.94e-23	6.65e-21	296
GO:004586220	Oral cavity	OSCC	positive regulation of proteolysis	236/7305	372/18723	6.53e-22	1.38e-19	236
GO:000697920	Oral cavity	OSCC	response to oxidative stress	273/7305	446/18723	8.35e-22	1.65e-19	273

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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

FBL

SNV

Missense_Mutation

c.823N>A

p.Ala275Thr

p.A275T

P22087

protein_coding

tolerated(0.08)

benign(0.375)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

FBL

SNV

Missense_Mutation

novel

c.214N>G

p.Arg72Gly

p.R72G

P22087

protein_coding

tolerated(0.88)

benign(0)

TCGA-BH-A0BL-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

FBL

SNV

Missense_Mutation

c.637N>T

p.Val213Leu

p.V213L

P22087

protein_coding

deleterious(0)

benign(0.015)

TCGA-D8-A13Z-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine

FBL

SNV

Missense_Mutation

rs754522515

c.653N>A

p.Arg218Gln

p.R218Q

P22087

protein_coding

deleterious(0.02)

possibly_damaging(0.872)

TCGA-E2-A152-01

Breast

breast invasive carcinoma

Female

<65

I/II

Targeted Molecular therapy

trastuzumab

FBL

insertion

In_Frame_Ins

novel

c.400_401insTCCAACACATGAACTTTGGGGGACACACTAGAACCGTAG

p.Tyr134delinsPheGlnHisMetAsnPheGlyGlyHisThrArgThrValAsp

p.Y134delinsFQHMNFGGHTRTVD

P22087

protein_coding

TCGA-A8-A0A6-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

epirubicin

FBL

SNV

Missense_Mutation

c.206A>T

p.Asn69Ile

p.N69I

P22087

protein_coding

tolerated(0.12)

benign(0.001)

TCGA-AA-3672-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Unknown

FBL

SNV

Missense_Mutation

rs762429726

c.61C>T

p.Arg21Cys

p.R21C

P22087

protein_coding

tolerated_low_confidence(0.06)

possibly_damaging(0.876)

TCGA-AA-3864-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

FBL

SNV

Missense_Mutation

novel

c.960G>T

p.Lys320Asn

p.K320N

P22087

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.855)

TCGA-CA-6717-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Chemotherapy

oxaliplatin

FBL

SNV

Missense_Mutation

c.476N>G

p.Pro159Arg

p.P159R

P22087

protein_coding

deleterious(0.02)

possibly_damaging(0.841)

TCGA-CK-4951-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

FBL

SNV

Missense_Mutation

novel

c.445C>A

p.Leu149Met

p.L149M

P22087

protein_coding

tolerated(0.11)

possibly_damaging(0.535)

TCGA-CM-6171-01

Colorectum

colon adenocarcinoma

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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