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: ABI1

Gene summary for ABI1

Gene summary.

Gene information	Species	Human
	Gene symbol	ABI1
	Gene ID	10006
	Gene name	abl interactor 1
	Gene Alias	ABI-1
	Cytomap	10p12.1
	Gene Type	protein-coding
	GO ID	GO:0000902
	UniProtAcc	Q8IZP0

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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
10006	ABI1	CA_HPV_3	Human	Cervix	CC	3.15e-05	5.77e-02	0.0414
10006	ABI1	N_HPV_2	Human	Cervix	N_HPV	6.46e-03	4.41e-02	-0.0131
10006	ABI1	CCI_1	Human	Cervix	CC	4.52e-03	1.14e+00	0.528
10006	ABI1	CCI_2	Human	Cervix	CC	3.34e-05	9.71e-01	0.5249
10006	ABI1	CCI_3	Human	Cervix	CC	1.12e-06	7.53e-01	0.516
10006	ABI1	Tumor	Human	Cervix	CC	1.31e-04	2.34e-01	0.1241
10006	ABI1	sample3	Human	Cervix	CC	4.26e-10	3.11e-01	0.1387
10006	ABI1	T3	Human	Cervix	CC	5.17e-09	3.27e-01	0.1389
10006	ABI1	HTA11_3410_2000001011	Human	Colorectum	AD	4.84e-13	-5.45e-01	0.0155
10006	ABI1	HTA11_7696_3000711011	Human	Colorectum	AD	7.60e-08	-3.81e-01	0.0674
10006	ABI1	HTA11_99999974143_84620	Human	Colorectum	MSS	1.12e-11	-4.51e-01	0.3005
10006	ABI1	A015-C-203	Human	Colorectum	FAP	2.19e-26	-3.81e-01	-0.1294
10006	ABI1	A015-C-204	Human	Colorectum	FAP	1.39e-02	-1.79e-01	-0.0228
10006	ABI1	A002-C-201	Human	Colorectum	FAP	1.71e-09	-3.14e-01	0.0324
10006	ABI1	A002-C-203	Human	Colorectum	FAP	5.21e-03	-9.97e-02	0.2786
10006	ABI1	A001-C-119	Human	Colorectum	FAP	5.17e-04	-3.03e-01	-0.1557
10006	ABI1	A001-C-108	Human	Colorectum	FAP	8.44e-14	-2.29e-01	-0.0272
10006	ABI1	A002-C-205	Human	Colorectum	FAP	1.98e-18	-4.46e-01	-0.1236
10006	ABI1	A015-C-005	Human	Colorectum	FAP	3.96e-06	-3.30e-01	-0.0336
10006	ABI1	A015-C-006	Human	Colorectum	FAP	1.32e-13	-4.64e-01	-0.0994

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
Colorectum (GSE201348)		FAP: Familial adenomatous polyposis
		CRC: Colorectal cancer
Colorectum (HTA11)		AD: Adenomas
		SER: Sessile serrated lesions
		MSI-H: Microsatellite-high colorectal cancer
		MSS: Microsatellite stable colorectal cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
Prostate		BPH: Benign Prostatic Hyperplasia
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ

∗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:000701510	Cervix	CC	actin filament organization	109/2311	442/18723	4.92e-13	2.45e-10	109
GO:003367410	Cervix	CC	positive regulation of kinase activity	101/2311	467/18723	8.66e-09	7.22e-07	101
GO:00975817	Cervix	CC	lamellipodium organization	31/2311	90/18723	4.57e-08	2.76e-06	31
GO:00458608	Cervix	CC	positive regulation of protein kinase activity	85/2311	386/18723	5.61e-08	3.29e-06	85
GO:003009910	Cervix	CC	myeloid cell differentiation	83/2311	381/18723	1.31e-07	6.42e-06	83
GO:00163587	Cervix	CC	dendrite development	58/2311	243/18723	4.52e-07	1.76e-05	58
GO:00081549	Cervix	CC	actin polymerization or depolymerization	51/2311	218/18723	4.05e-06	1.05e-04	51
GO:00488135	Cervix	CC	dendrite morphogenesis	30/2311	146/18723	3.27e-03	2.13e-02	30
GO:003009925	Cervix	N_HPV	myeloid cell differentiation	33/534	381/18723	1.61e-08	2.52e-06	33
GO:000701525	Cervix	N_HPV	actin filament organization	29/534	442/18723	3.00e-05	8.02e-04	29
GO:00615151	Cervix	N_HPV	myeloid cell development	10/534	71/18723	3.17e-05	8.16e-04	10
GO:00987511	Cervix	N_HPV	bone cell development	7/534	34/18723	4.07e-05	9.70e-04	7
GO:00603482	Cervix	N_HPV	bone development	15/534	205/18723	8.27e-04	1.02e-02	15
GO:004586023	Cervix	N_HPV	positive regulation of protein kinase activity	22/534	386/18723	1.73e-03	1.75e-02	22
GO:003367422	Cervix	N_HPV	positive regulation of kinase activity	25/534	467/18723	2.05e-03	1.98e-02	25
GO:0030219	Cervix	N_HPV	megakaryocyte differentiation	6/534	57/18723	5.54e-03	3.94e-02	6
GO:0007015	Colorectum	AD	actin filament organization	167/3918	442/18723	1.65e-16	7.94e-14	167
GO:0008154	Colorectum	AD	actin polymerization or depolymerization	90/3918	218/18723	6.14e-12	8.23e-10	90
GO:0030099	Colorectum	AD	myeloid cell differentiation	119/3918	381/18723	1.24e-06	4.01e-05	119
GO:0097581	Colorectum	AD	lamellipodium organization	35/3918	90/18723	7.39e-05	1.18e-03	35

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0513020	Cervix	CC	Pathogenic Escherichia coli infection	63/1267	197/8465	9.28e-10	2.00e-08	1.19e-08	63
hsa0513220	Cervix	CC	Salmonella infection	74/1267	249/8465	1.33e-09	2.54e-08	1.50e-08	74
hsa05130110	Cervix	CC	Pathogenic Escherichia coli infection	63/1267	197/8465	9.28e-10	2.00e-08	1.19e-08	63
hsa05132110	Cervix	CC	Salmonella infection	74/1267	249/8465	1.33e-09	2.54e-08	1.50e-08	74
hsa0513044	Cervix	N_HPV	Pathogenic Escherichia coli infection	25/349	197/8465	4.71e-07	8.00e-06	6.25e-06	25
hsa0513244	Cervix	N_HPV	Salmonella infection	28/349	249/8465	1.18e-06	1.64e-05	1.28e-05	28
hsa0513054	Cervix	N_HPV	Pathogenic Escherichia coli infection	25/349	197/8465	4.71e-07	8.00e-06	6.25e-06	25
hsa0513254	Cervix	N_HPV	Salmonella infection	28/349	249/8465	1.18e-06	1.64e-05	1.28e-05	28
hsa051324	Colorectum	MSS	Salmonella infection	92/1875	249/8465	5.23e-08	9.74e-07	5.97e-07	92
hsa051304	Colorectum	MSS	Pathogenic Escherichia coli infection	73/1875	197/8465	1.10e-06	1.48e-05	9.06e-06	73
hsa051325	Colorectum	MSS	Salmonella infection	92/1875	249/8465	5.23e-08	9.74e-07	5.97e-07	92
hsa051305	Colorectum	MSS	Pathogenic Escherichia coli infection	73/1875	197/8465	1.10e-06	1.48e-05	9.06e-06	73
hsa051308	Colorectum	FAP	Pathogenic Escherichia coli infection	62/1404	197/8465	1.37e-07	3.08e-06	1.87e-06	62
hsa051328	Colorectum	FAP	Salmonella infection	67/1404	249/8465	2.04e-05	2.52e-04	1.53e-04	67
hsa051309	Colorectum	FAP	Pathogenic Escherichia coli infection	62/1404	197/8465	1.37e-07	3.08e-06	1.87e-06	62
hsa051329	Colorectum	FAP	Salmonella infection	67/1404	249/8465	2.04e-05	2.52e-04	1.53e-04	67
hsa0513010	Colorectum	CRC	Pathogenic Escherichia coli infection	47/1091	197/8465	1.49e-05	3.84e-04	2.60e-04	47
hsa0513210	Colorectum	CRC	Salmonella infection	48/1091	249/8465	2.43e-03	1.69e-02	1.15e-02	48
hsa0513011	Colorectum	CRC	Pathogenic Escherichia coli infection	47/1091	197/8465	1.49e-05	3.84e-04	2.60e-04	47
hsa0513211	Colorectum	CRC	Salmonella infection	48/1091	249/8465	2.43e-03	1.69e-02	1.15e-02	48

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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

ABI1

SNV

Missense_Mutation

c.356N>T

p.Ser119Leu

p.S119L

Q8IZP0

protein_coding

tolerated(0.18)

benign(0.021)

TCGA-A8-A095-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

ABI1

SNV

Missense_Mutation

rs772279539

c.980N>T

p.Ser327Leu

p.S327L

Q8IZP0

protein_coding

tolerated(0.2)

probably_damaging(0.99)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ABI1

SNV

Missense_Mutation

c.1240N>T

p.Pro414Ser

p.P414S

Q8IZP0

protein_coding

deleterious(0.03)

possibly_damaging(0.802)

TCGA-BH-A0H9-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

ABI1

SNV

Missense_Mutation

rs752428017

c.895G>T

p.Val299Leu

p.V299L

Q8IZP0

protein_coding

tolerated(0.74)

benign(0)

TCGA-E2-A14N-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

ABI1

insertion

Nonsense_Mutation

novel

c.720-1_720insGAGAGCATTGAATTAGCCCCTTGAT

p.Ser240ArgfsTer6

p.S240Rfs*6

Q8IZP0

protein_coding

TCGA-B6-A0I6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ABI1

SNV

Missense_Mutation

novel

c.1015G>A

p.Val339Met

p.V339M

Q8IZP0

protein_coding

deleterious(0)

benign(0.04)

TCGA-EA-A410-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

ABI1

SNV

Missense_Mutation

c.830N>G

p.Ser277Cys

p.S277C

Q8IZP0

protein_coding

tolerated(0.1)

possibly_damaging(0.7)

TCGA-IR-A3LH-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

ABI1

SNV

Missense_Mutation

novel

c.1031C>T

p.Ser344Phe

p.S344F

Q8IZP0

protein_coding

tolerated(0.13)

possibly_damaging(0.477)

TCGA-VS-A8EK-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

cisplatin

ABI1

SNV

Missense_Mutation

novel

c.1387N>A

p.Asp463Asn

p.D463N

Q8IZP0

protein_coding

tolerated(0.21)

probably_damaging(1)

TCGA-VS-A958-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

ABI1

SNV

Missense_Mutation

c.1265N>C

p.Glu422Ala

p.E422A

Q8IZP0

protein_coding

tolerated(0.09)

benign(0.118)

TCGA-AA-3977-01

Colorectum

colon adenocarcinoma

Male

>=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
10006	ABI1	CLINICALLY ACTIONABLE, KINASE		dasatinib	DASATINIB
10006	ABI1	CLINICALLY ACTIONABLE, KINASE		ponatinib	PONATINIB

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