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: SLA

Gene summary for SLA

Gene summary.

Gene information	Species	Human
	Gene symbol	SLA
	Gene ID	6503
	Gene name	Src like adaptor
	Gene Alias	SLA1
	Cytomap	8q24.22
	Gene Type	protein-coding
	GO ID	GO:0002376
	UniProtAcc	Q13239

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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
6503	SLA	PTC01	Human	Thyroid	PTC	1.01e-03	1.11e-01	0.1899
6503	SLA	PTC04	Human	Thyroid	PTC	5.58e-07	2.35e-01	0.1927
6503	SLA	PTC06	Human	Thyroid	PTC	2.86e-17	5.34e-01	0.2057
6503	SLA	PTC07	Human	Thyroid	PTC	2.19e-11	3.25e-01	0.2044

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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:1902903	Colorectum	AD	regulation of supramolecular fiber organization	139/3918	383/18723	2.01e-12	3.19e-10	139
GO:0032271	Colorectum	AD	regulation of protein polymerization	94/3918	233/18723	1.01e-11	1.29e-09	94
GO:0051258	Colorectum	AD	protein polymerization	112/3918	297/18723	1.85e-11	2.27e-09	112
GO:0043254	Colorectum	AD	regulation of protein-containing complex assembly	148/3918	428/18723	2.64e-11	3.18e-09	148
GO:1902905	Colorectum	AD	positive regulation of supramolecular fiber organization	85/3918	209/18723	5.95e-11	6.33e-09	85
GO:0051495	Colorectum	AD	positive regulation of cytoskeleton organization	89/3918	226/18723	1.61e-10	1.56e-08	89
GO:0032273	Colorectum	AD	positive regulation of protein polymerization	62/3918	138/18723	1.94e-10	1.76e-08	62
GO:0031334	Colorectum	AD	positive regulation of protein-containing complex assembly	91/3918	237/18723	4.78e-10	3.99e-08	91
GO:0070507	Colorectum	AD	regulation of microtubule cytoskeleton organization	44/3918	148/18723	7.05e-03	4.31e-02	44
GO:19029032	Colorectum	MSS	regulation of supramolecular fiber organization	121/3467	383/18723	3.63e-10	3.28e-08	121
GO:00322712	Colorectum	MSS	regulation of protein polymerization	83/3467	233/18723	3.99e-10	3.49e-08	83
GO:00432542	Colorectum	MSS	regulation of protein-containing complex assembly	130/3467	428/18723	1.38e-09	1.03e-07	130
GO:19029052	Colorectum	MSS	positive regulation of supramolecular fiber organization	75/3467	209/18723	1.89e-09	1.35e-07	75
GO:00313342	Colorectum	MSS	positive regulation of protein-containing complex assembly	82/3467	237/18723	2.49e-09	1.75e-07	82
GO:00512582	Colorectum	MSS	protein polymerization	97/3467	297/18723	2.98e-09	2.07e-07	97
GO:00322732	Colorectum	MSS	positive regulation of protein polymerization	55/3467	138/18723	3.84e-09	2.55e-07	55
GO:00514952	Colorectum	MSS	positive regulation of cytoskeleton organization	78/3467	226/18723	6.86e-09	4.32e-07	78
GO:00432544	Colorectum	FAP	regulation of protein-containing complex assembly	101/2622	428/18723	5.18e-08	4.07e-06	101
GO:19029034	Colorectum	FAP	regulation of supramolecular fiber organization	92/2622	383/18723	8.48e-08	5.77e-06	92
GO:00322714	Colorectum	FAP	regulation of protein polymerization	62/2622	233/18723	2.64e-07	1.53e-05	62

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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

SLA

SNV

Missense_Mutation

rs772449159

c.142N>C

p.Thr48Pro

p.T48P

Q13239

protein_coding

tolerated(0.27)

benign(0.005)

TCGA-A2-A1G4-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

adriamycin

SLA

SNV

Missense_Mutation

rs772449159

c.142A>C

p.Thr48Pro

p.T48P

Q13239

protein_coding

tolerated(0.27)

benign(0.005)

TCGA-A8-A06R-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

5-fluorouracil

SLA

SNV

Missense_Mutation

c.278N>G

p.Ser93Cys

p.S93C

Q13239

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SLA

SNV

Missense_Mutation

rs772449159

c.142A>C

p.Thr48Pro

p.T48P

Q13239

protein_coding

tolerated(0.27)

benign(0.005)

TCGA-BH-A1F5-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SLA

SNV

Missense_Mutation

rs772449159

c.142N>C

p.Thr48Pro

p.T48P

Q13239

protein_coding

tolerated(0.27)

benign(0.005)

TCGA-C8-A273-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

SLA

SNV

Missense_Mutation

rs767082161

c.808N>G

p.Arg270Gly

p.R270G

Q13239

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-D8-A27G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SLA

SNV

Missense_Mutation

rs772449159

c.142A>C

p.Thr48Pro

p.T48P

Q13239

protein_coding

tolerated(0.27)

benign(0.005)

TCGA-E9-A1RE-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

tamoxiphen

SLA

SNV

Missense_Mutation

rs772449159

c.142A>C

p.Thr48Pro

p.T48P

Q13239

protein_coding

tolerated(0.27)

benign(0.005)

TCGA-E9-A22A-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

SLA

SNV

Missense_Mutation

rs376259266

c.157G>A

p.Glu53Lys

p.E53K

Q13239

protein_coding

tolerated(0.11)

possibly_damaging(0.572)

TCGA-JX-A3Q0-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unknown

SLA

SNV

Missense_Mutation

novel

c.944N>T

p.Glu315Val

p.E315V

Q13239

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.998)

TCGA-VS-A94Z-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

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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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