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: ANK2

Gene summary for ANK2

Gene summary.

Gene information	Species	Human
	Gene symbol	ANK2
	Gene ID	287
	Gene name	ankyrin 2
	Gene Alias	ANK-2
	Cytomap	4q25-q26
	Gene Type	protein-coding
	GO ID	GO:0001508
	UniProtAcc	Q01484

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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
287	ANK2	ATC13	Human	Thyroid	ATC	2.28e-36	7.42e-01	0.34
287	ANK2	ATC5	Human	Thyroid	ATC	7.88e-38	8.07e-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:0009117111	Esophagus	ESCC	nucleotide metabolic process	282/8552	489/18723	4.70e-08	8.50e-07	282
GO:0009259111	Esophagus	ESCC	ribonucleotide metabolic process	224/8552	385/18723	4.41e-07	6.00e-06	224
GO:0072521111	Esophagus	ESCC	purine-containing compound metabolic process	238/8552	416/18723	1.20e-06	1.49e-05	238
GO:0009150111	Esophagus	ESCC	purine ribonucleotide metabolic process	213/8552	368/18723	1.40e-06	1.69e-05	213
GO:0046390110	Esophagus	ESCC	ribose phosphate biosynthetic process	119/8552	190/18723	1.73e-06	2.06e-05	119
GO:0006163111	Esophagus	ESCC	purine nucleotide metabolic process	226/8552	396/18723	2.81e-06	3.21e-05	226
GO:000916516	Esophagus	ESCC	nucleotide biosynthetic process	150/8552	254/18723	1.12e-05	1.06e-04	150
GO:0009260110	Esophagus	ESCC	ribonucleotide biosynthetic process	112/8552	182/18723	1.12e-05	1.06e-04	112
GO:190129316	Esophagus	ESCC	nucleoside phosphate biosynthetic process	151/8552	256/18723	1.15e-05	1.08e-04	151
GO:00338664	Esophagus	ESCC	nucleoside bisphosphate biosynthetic process	44/8552	60/18723	1.25e-05	1.15e-04	44
GO:00340304	Esophagus	ESCC	ribonucleoside bisphosphate biosynthetic process	44/8552	60/18723	1.25e-05	1.15e-04	44
GO:00340334	Esophagus	ESCC	purine nucleoside bisphosphate biosynthetic process	44/8552	60/18723	1.25e-05	1.15e-04	44
GO:007252217	Esophagus	ESCC	purine-containing compound biosynthetic process	120/8552	200/18723	3.02e-05	2.51e-04	120
GO:00066318	Esophagus	ESCC	fatty acid metabolic process	217/8552	390/18723	4.21e-05	3.39e-04	217
GO:0009152110	Esophagus	ESCC	purine ribonucleotide biosynthetic process	103/8552	169/18723	4.40e-05	3.51e-04	103
GO:005188110	Esophagus	ESCC	regulation of mitochondrial membrane potential	51/8552	74/18723	4.42e-05	3.51e-04	51
GO:00065757	Esophagus	ESCC	cellular modified amino acid metabolic process	112/8552	188/18723	8.31e-05	6.06e-04	112
GO:000616417	Esophagus	ESCC	purine nucleotide biosynthetic process	113/8552	191/18723	1.16e-04	8.04e-04	113
GO:00705848	Esophagus	ESCC	mitochondrion morphogenesis	18/8552	21/18723	1.81e-04	1.16e-03	18
GO:00067671	Esophagus	ESCC	water-soluble vitamin metabolic process	41/8552	59/18723	1.84e-04	1.17e-03	41

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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

ANK2

SNV

Missense_Mutation

rs775323997

c.3094N>A

p.Glu1032Lys

p.E1032K

Q01484

protein_coding

deleterious(0)

probably_damaging(0.962)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

ANK2

SNV

Missense_Mutation

novel

c.6349N>A

p.Asp2117Asn

p.D2117N

Q01484

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.642)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

ANK2

SNV

Missense_Mutation

c.2728C>G

p.Leu910Val

p.L910V

Q01484

protein_coding

tolerated(0.07)

benign(0.135)

TCGA-A2-A0CT-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cytoxan

ANK2

SNV

Missense_Mutation

rs754722115

c.4280N>A

p.Arg1427Gln

p.R1427Q

Q01484

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-A7-A4SC-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

ANK2

SNV

Missense_Mutation

rs367592943

c.5827G>A

p.Gly1943Arg

p.G1943R

Q01484

protein_coding

deleterious_low_confidence(0.01)

possibly_damaging(0.506)

TCGA-A8-A06T-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

anastrozole

ANK2

SNV

Missense_Mutation

c.4222N>A

p.Glu1408Lys

p.E1408K

Q01484

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ANK2

SNV

Missense_Mutation

c.7868N>A

p.Ser2623Tyr

p.S2623Y

Q01484

protein_coding

tolerated_low_confidence(0.83)

possibly_damaging(0.66)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ANK2

SNV

Missense_Mutation

novel

c.6215C>A

p.Ser2072Tyr

p.S2072Y

Q01484

protein_coding

tolerated_low_confidence(0.07)

benign(0.367)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ANK2

SNV

Missense_Mutation

novel

c.7594G>T

p.Gly2532Trp

p.G2532W

Q01484

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ANK2

SNV

Missense_Mutation

novel

c.8177C>A

p.Thr2726Asn

p.T2726N

Q01484

protein_coding

tolerated_low_confidence(0.51)

benign(0)

TCGA-AN-A046-01

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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