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: PLP1

Gene summary for PLP1

Gene summary.

Gene information	Species	Human
	Gene symbol	PLP1
	Gene ID	5354
	Gene name	proteolipid protein 1
	Gene Alias	GPM6C
	Cytomap	Xq22.2
	Gene Type	protein-coding
	GO ID	GO:0001676
	UniProtAcc	A8K9L3

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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
5354	PLP1	ATC13	Human	Thyroid	ATC	2.80e-17	5.30e-01	0.34
5354	PLP1	ATC5	Human	Thyroid	ATC	1.20e-21	5.73e-01	0.34

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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:004586018	Esophagus	ESCC	positive regulation of protein kinase activity	219/8552	386/18723	6.91e-06	6.97e-05	219
GO:003367420	Esophagus	ESCC	positive regulation of kinase activity	260/8552	467/18723	7.26e-06	7.22e-05	260
GO:000641419	Esophagus	ESCC	translational elongation	41/8552	55/18723	1.26e-05	1.16e-04	41
GO:00021817	Liver	NAFLD	cytoplasmic translation	93/1882	148/18723	1.44e-55	8.41e-52	93
GO:00458606	Liver	NAFLD	positive regulation of protein kinase activity	65/1882	386/18723	2.22e-05	6.13e-04	65
GO:00336747	Liver	NAFLD	positive regulation of kinase activity	74/1882	467/18723	5.16e-05	1.19e-03	74
GO:00064145	Liver	NAFLD	translational elongation	16/1882	55/18723	6.71e-05	1.44e-03	16
GO:0032147	Liver	NAFLD	activation of protein kinase activity	24/1882	134/18723	3.66e-03	3.13e-02	24
GO:000218112	Liver	Cirrhotic	cytoplasmic translation	120/4634	148/18723	2.95e-47	1.85e-43	120
GO:004586011	Liver	Cirrhotic	positive regulation of protein kinase activity	117/4634	386/18723	7.07e-03	3.41e-02	117
GO:000218122	Liver	HCC	cytoplasmic translation	132/7958	148/18723	9.09e-33	5.76e-30	132
GO:000641412	Liver	HCC	translational elongation	36/7958	55/18723	4.94e-04	3.23e-03	36
GO:004586021	Liver	HCC	positive regulation of protein kinase activity	194/7958	386/18723	1.16e-03	6.54e-03	194
GO:003367411	Liver	HCC	positive regulation of kinase activity	230/7958	467/18723	1.72e-03	8.95e-03	230
GO:00321471	Liver	HCC	activation of protein kinase activity	72/7958	134/18723	5.61e-03	2.33e-02	72
GO:000218132	Liver	Cyst	cytoplasmic translation	70/496	148/18723	9.01e-71	3.85e-67	70
GO:000641421	Liver	Cyst	translational elongation	7/496	55/18723	5.93e-04	1.71e-02	7
GO:000218120	Oral cavity	OSCC	cytoplasmic translation	133/7305	148/18723	1.94e-38	2.46e-35	133
GO:004586016	Oral cavity	OSCC	positive regulation of protein kinase activity	194/7305	386/18723	3.90e-06	4.59e-05	194
GO:003367418	Oral cavity	OSCC	positive regulation of kinase activity	228/7305	467/18723	8.31e-06	8.90e-05	228

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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

PLP1

SNV

Missense_Mutation

novel

c.49N>C

p.Ala17Pro

p.A17P

P60201

protein_coding

tolerated(0.15)

probably_damaging(0.998)

TCGA-A8-A0A7-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PLP1

SNV

Missense_Mutation

c.743N>A

p.Ala248Glu

p.A248E

P60201

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-E9-A243-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

PLP1

insertion

Nonsense_Mutation

novel

c.267_268insCATGTCTGAAGGGTGGGGCAGGGAGAGTAGGTCCCT

p.Glu89_Gly90insHisValTerArgValGlyGlnGlyGluTerValPro

p.E89_G90insHV*RVGQGE*VP

P60201

protein_coding

TCGA-A8-A07R-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Ancillary

zoledronic

PLP1

insertion

Frame_Shift_Ins

novel

c.160_161insCTGTGTCTTTTCTCTCTTC

p.Asn54ThrfsTer12

p.N54Tfs*12

P60201

protein_coding

TCGA-AN-A0FN-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PLP1

insertion

Frame_Shift_Ins

novel

c.161_162insTATCCCGTATAACACCCAGCATAATG

p.Tyr55IlefsTer19

p.Y55Ifs*19

P60201

protein_coding

TCGA-AN-A0FN-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PLP1

SNV

Missense_Mutation

c.391C>G

p.Gln131Glu

p.Q131E

P60201

protein_coding

tolerated_low_confidence(1)

benign(0.003)

TCGA-C5-A2LZ-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Unknown

PLP1

SNV

Missense_Mutation

novel

c.611N>T

p.Ala204Val

p.A204V

P60201

protein_coding

tolerated(0.55)

possibly_damaging(0.87)

TCGA-DS-A1OB-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

carboplatin

PLP1

SNV

Missense_Mutation

c.307G>A

p.Asp103Asn

p.D103N

P60201

protein_coding

deleterious(0.02)

possibly_damaging(0.515)

TCGA-AA-3815-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

PLP1

SNV

Missense_Mutation

c.709N>A

p.Phe237Ile

p.F237I

P60201

protein_coding

deleterious(0)

benign(0.138)

TCGA-CK-4951-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

PLP1

SNV

Missense_Mutation

novel

c.346A>T

p.Thr116Ser

p.T116S

P60201

protein_coding

tolerated(0.37)

possibly_damaging(0.527)

TCGA-CM-5868-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Chemotherapy

fluorouracil

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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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