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:000218110	Cervix	CC	cytoplasmic translation	96/2311	148/18723	4.87e-51	2.91e-47	96
GO:003367410	Cervix	CC	positive regulation of kinase activity	101/2311	467/18723	8.66e-09	7.22e-07	101
GO:00458608	Cervix	CC	positive regulation of protein kinase activity	85/2311	386/18723	5.61e-08	3.29e-06	85
GO:000218115	Cervix	HSIL_HPV	cytoplasmic translation	86/737	148/18723	3.97e-82	1.91e-78	86
GO:003367413	Cervix	HSIL_HPV	positive regulation of kinase activity	34/737	467/18723	4.49e-04	6.63e-03	34
GO:004586013	Cervix	HSIL_HPV	positive regulation of protein kinase activity	27/737	386/18723	2.93e-03	2.74e-02	27
GO:00064148	Cervix	HSIL_HPV	translational elongation	7/737	55/18723	5.59e-03	4.47e-02	7
GO:0002181	Colorectum	AD	cytoplasmic translation	109/3918	148/18723	3.40e-43	2.13e-39	109
GO:0033674	Colorectum	AD	positive regulation of kinase activity	131/3918	467/18723	1.28e-04	1.85e-03	131
GO:0045860	Colorectum	AD	positive regulation of protein kinase activity	107/3918	386/18723	8.01e-04	7.92e-03	107
GO:0006414	Colorectum	AD	translational elongation	21/3918	55/18723	2.53e-03	1.93e-02	21
GO:00021811	Colorectum	SER	cytoplasmic translation	102/2897	148/18723	1.38e-48	8.49e-45	102
GO:00336741	Colorectum	SER	positive regulation of kinase activity	95/2897	467/18723	2.62e-03	2.41e-02	95
GO:00064141	Colorectum	SER	translational elongation	17/2897	55/18723	3.00e-03	2.65e-02	17
GO:00458601	Colorectum	SER	positive regulation of protein kinase activity	79/2897	386/18723	4.85e-03	3.79e-02	79
GO:00021812	Colorectum	MSS	cytoplasmic translation	108/3467	148/18723	1.78e-47	1.11e-43	108
GO:00336742	Colorectum	MSS	positive regulation of kinase activity	122/3467	467/18723	2.50e-05	5.21e-04	122
GO:00458602	Colorectum	MSS	positive regulation of protein kinase activity	102/3467	386/18723	6.93e-05	1.20e-03	102
GO:00064142	Colorectum	MSS	translational elongation	19/3467	55/18723	3.47e-03	2.59e-02	19
GO:00021813	Colorectum	MSI-H	cytoplasmic translation	100/1319	148/18723	1.50e-79	8.31e-76	100

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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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