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: PER2

Gene summary for PER2

Gene summary.

Gene information	Species	Human
	Gene symbol	PER2
	Gene ID	8864
	Gene name	period circadian regulator 2
	Gene Alias	FASPS
	Cytomap	2q37.3
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	O15055

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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
8864	PER2	GSM4909297	Human	Breast	IDC	1.63e-03	2.13e-01	0.1517
8864	PER2	GSM4909311	Human	Breast	IDC	2.19e-04	-1.30e-01	0.1534
8864	PER2	GSM4909319	Human	Breast	IDC	1.14e-05	-1.55e-01	0.1563
8864	PER2	brca1	Human	Breast	Precancer	2.70e-02	-1.59e-01	-0.0338
8864	PER2	P1	Human	Breast	IDC	2.94e-02	-9.14e-02	0.1527
8864	PER2	DCIS2	Human	Breast	DCIS	1.25e-88	7.59e-01	0.0085
8864	PER2	LZE4T	Human	Esophagus	ESCC	4.65e-04	3.14e-02	0.0811
8864	PER2	LZE5T	Human	Esophagus	ESCC	3.77e-04	5.04e-02	0.0514
8864	PER2	LZE20T	Human	Esophagus	ESCC	1.27e-05	-4.33e-02	0.0662
8864	PER2	LZE24T	Human	Esophagus	ESCC	3.78e-08	4.64e-01	0.0596
8864	PER2	P2T-E	Human	Esophagus	ESCC	2.17e-14	1.71e-01	0.1177
8864	PER2	P4T-E	Human	Esophagus	ESCC	4.79e-11	-2.68e-02	0.1323
8864	PER2	P5T-E	Human	Esophagus	ESCC	6.08e-06	-8.67e-02	0.1327
8864	PER2	P8T-E	Human	Esophagus	ESCC	4.76e-20	3.83e-01	0.0889
8864	PER2	P9T-E	Human	Esophagus	ESCC	4.70e-08	3.58e-01	0.1131
8864	PER2	P10T-E	Human	Esophagus	ESCC	5.18e-05	2.80e-02	0.116
8864	PER2	P11T-E	Human	Esophagus	ESCC	1.19e-02	-2.21e-02	0.1426
8864	PER2	P12T-E	Human	Esophagus	ESCC	7.46e-14	2.15e-01	0.1122
8864	PER2	P15T-E	Human	Esophagus	ESCC	4.17e-13	4.56e-01	0.1149
8864	PER2	P16T-E	Human	Esophagus	ESCC	2.82e-06	-5.56e-02	0.1153

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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
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
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:000762320	Skin	AK	circadian rhythm	51/1910	210/18723	2.80e-09	2.40e-07	51
GO:005109826	Skin	AK	regulation of binding	74/1910	363/18723	4.40e-09	3.30e-07	74
GO:00165709	Skin	AK	histone modification	84/1910	463/18723	1.10e-07	4.95e-06	84
GO:003292216	Skin	AK	circadian regulation of gene expression	23/1910	68/18723	1.18e-07	5.24e-06	23
GO:000931420	Skin	AK	response to radiation	78/1910	456/18723	3.32e-06	8.59e-05	78
GO:005076713	Skin	AK	regulation of neurogenesis	65/1910	364/18723	5.10e-06	1.19e-04	65
GO:005110126	Skin	AK	regulation of DNA binding	28/1910	118/18723	1.60e-05	3.09e-04	28
GO:004275210	Skin	AK	regulation of circadian rhythm	28/1910	121/18723	2.62e-05	4.65e-04	28
GO:00519607	Skin	AK	regulation of nervous system development	72/1910	443/18723	4.53e-05	7.11e-04	72
GO:004544410	Skin	AK	fat cell differentiation	43/1910	229/18723	5.87e-05	8.75e-04	43
GO:0009648	Skin	AK	photoperiodism	11/1910	33/18723	2.79e-04	2.94e-03	11
GO:20006773	Skin	AK	regulation of transcription regulatory region DNA binding	14/1910	50/18723	3.43e-04	3.46e-03	14
GO:00096492	Skin	AK	entrainment of circadian clock	11/1910	34/18723	3.75e-04	3.63e-03	11
GO:0043153	Skin	AK	entrainment of circadian clock by photoperiod	10/1910	29/18723	3.86e-04	3.70e-03	10
GO:005110024	Skin	AK	negative regulation of binding	29/1910	162/18723	1.89e-03	1.29e-02	29
GO:000609126	Skin	AK	generation of precursor metabolites and energy	69/1910	490/18723	3.59e-03	2.16e-02	69
GO:00094166	Skin	AK	response to light stimulus	48/1910	320/18723	4.20e-03	2.45e-02	48
GO:0009314110	Skin	SCCIS	response to radiation	50/919	456/18723	9.08e-08	1.27e-05	50
GO:1903320112	Skin	SCCIS	regulation of protein modification by small protein conjugation or removal	32/919	242/18723	3.31e-07	3.03e-05	32
GO:0031397112	Skin	SCCIS	negative regulation of protein ubiquitination	17/919	83/18723	4.60e-07	3.77e-05	17

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa052215	Esophagus	ESCC	Acute myeloid leukemia	49/4205	67/8465	7.43e-05	3.07e-04	1.57e-04	49
hsa052028	Esophagus	ESCC	Transcriptional misregulation in cancer	116/4205	193/8465	2.08e-03	5.95e-03	3.05e-03	116
hsa047105	Esophagus	ESCC	Circadian rhythm	24/4205	34/8465	1.09e-02	2.51e-02	1.29e-02	24
hsa0522113	Esophagus	ESCC	Acute myeloid leukemia	49/4205	67/8465	7.43e-05	3.07e-04	1.57e-04	49
hsa0520213	Esophagus	ESCC	Transcriptional misregulation in cancer	116/4205	193/8465	2.08e-03	5.95e-03	3.05e-03	116
hsa0471012	Esophagus	ESCC	Circadian rhythm	24/4205	34/8465	1.09e-02	2.51e-02	1.29e-02	24
hsa052026	Lung	IAC	Transcriptional misregulation in cancer	40/1053	193/8465	6.90e-04	5.90e-03	3.92e-03	40
hsa04710	Lung	IAC	Circadian rhythm	10/1053	34/8465	6.70e-03	2.76e-02	1.83e-02	10
hsa0520211	Lung	IAC	Transcriptional misregulation in cancer	40/1053	193/8465	6.90e-04	5.90e-03	3.92e-03	40
hsa047101	Lung	IAC	Circadian rhythm	10/1053	34/8465	6.70e-03	2.76e-02	1.83e-02	10
hsa052022	Lung	AIS	Transcriptional misregulation in cancer	39/961	193/8465	2.15e-04	2.41e-03	1.54e-03	39
hsa047102	Lung	AIS	Circadian rhythm	11/961	34/8465	9.22e-04	7.11e-03	4.55e-03	11
hsa052023	Lung	AIS	Transcriptional misregulation in cancer	39/961	193/8465	2.15e-04	2.41e-03	1.54e-03	39
hsa047103	Lung	AIS	Circadian rhythm	11/961	34/8465	9.22e-04	7.11e-03	4.55e-03	11
hsa052024	Lung	MIAC	Transcriptional misregulation in cancer	22/507	193/8465	2.64e-03	2.26e-02	1.64e-02	22
hsa052212	Lung	MIAC	Acute myeloid leukemia	10/507	67/8465	6.16e-03	4.07e-02	2.95e-02	10
hsa052025	Lung	MIAC	Transcriptional misregulation in cancer	22/507	193/8465	2.64e-03	2.26e-02	1.64e-02	22
hsa0522111	Lung	MIAC	Acute myeloid leukemia	10/507	67/8465	6.16e-03	4.07e-02	2.95e-02	10
hsa047104	Prostate	BPH	Circadian rhythm	15/1718	34/8465	1.40e-03	5.85e-03	3.62e-03	15
hsa052027	Prostate	BPH	Transcriptional misregulation in cancer	53/1718	193/8465	9.56e-03	2.92e-02	1.81e-02	53

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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

PER2

SNV

Missense_Mutation

novel

c.208G>A

p.Glu70Lys

p.E70K

O15055

protein_coding

tolerated(0.31)

possibly_damaging(0.601)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

PER2

SNV

Missense_Mutation

novel

c.913G>A

p.Glu305Lys

p.E305K

O15055

protein_coding

deleterious(0.04)

benign(0.009)

TCGA-A1-A0SI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PER2

SNV

Missense_Mutation

c.505N>C

p.Asp169His

p.D169H

O15055

protein_coding

deleterious(0.05)

benign(0.062)

TCGA-A2-A0YK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

PER2

SNV

Missense_Mutation

novel

c.1843G>T

p.Ala615Ser

p.A615S

O15055

protein_coding

tolerated(1)

benign(0)

TCGA-A7-A0CJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

PER2

SNV

Missense_Mutation

c.1102N>A

p.Val368Met

p.V368M

O15055

protein_coding

tolerated(0.09)

benign(0.233)

TCGA-AO-A128-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

PER2

SNV

Missense_Mutation

c.1258N>T

p.Pro420Ser

p.P420S

O15055

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

PER2

SNV

Missense_Mutation

c.697N>T

p.Pro233Ser

p.P233S

O15055

protein_coding

deleterious(0.02)

probably_damaging(1)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

PER2

SNV

Missense_Mutation

rs748039327

c.3670N>A

p.Glu1224Lys

p.E1224K

O15055

protein_coding

deleterious(0.01)

possibly_damaging(0.689)

TCGA-D8-A1J8-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

nolvadex

PER2

insertion

Frame_Shift_Ins

novel

c.1841_1842insTCCTATGAATAAACATTGGGGACAA

p.Ala615ProfsTer14

p.A615Pfs*14

O15055

protein_coding

TCGA-A7-A0CJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

PER2

insertion

In_Frame_Ins

novel

c.3477_3478insCTTATCAGGCCCCAGCTGGTGGGTTGGCAGATTGTCTGGGTT

p.Glu1159_Ala1160insLeuIleArgProGlnLeuValGlyTrpGlnIleValTrpVal

p.E1159_A1160insLIRPQLVGWQIVWV

O15055

protein_coding

TCGA-AN-A04C-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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