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: KIF22

Gene summary for KIF22

Gene summary.

Gene information	Species	Human
	Gene symbol	KIF22
	Gene ID	3835
	Gene name	kinesin family member 22
	Gene Alias	A-328A3.2
	Cytomap	16p11.2
	Gene Type	protein-coding
	GO ID	GO:0000070
	UniProtAcc	A0A024R632

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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
3835	KIF22	GSM4909290	Human	Breast	IDC	1.28e-09	4.00e-01	0.2096
3835	KIF22	GSM4909291	Human	Breast	IDC	9.01e-08	3.94e-01	0.1753
3835	KIF22	GSM4909293	Human	Breast	IDC	2.13e-15	4.48e-01	0.1581
3835	KIF22	GSM4909294	Human	Breast	IDC	1.77e-02	2.31e-01	0.2022
3835	KIF22	GSM4909296	Human	Breast	IDC	4.51e-05	2.96e-01	0.1524
3835	KIF22	GSM4909301	Human	Breast	IDC	4.90e-27	7.12e-01	0.1577
3835	KIF22	GSM4909304	Human	Breast	IDC	3.99e-33	6.54e-01	0.1636
3835	KIF22	GSM4909306	Human	Breast	IDC	5.94e-49	9.21e-01	0.1564
3835	KIF22	GSM4909307	Human	Breast	IDC	2.53e-03	2.97e-01	0.1569
3835	KIF22	GSM4909311	Human	Breast	IDC	9.05e-12	1.41e-01	0.1534
3835	KIF22	GSM4909313	Human	Breast	IDC	2.04e-03	2.08e-01	0.0391
3835	KIF22	GSM4909317	Human	Breast	IDC	2.37e-02	2.17e-01	0.1355
3835	KIF22	GSM4909319	Human	Breast	IDC	3.44e-10	1.49e-01	0.1563
3835	KIF22	GSM4909321	Human	Breast	IDC	1.52e-05	2.60e-01	0.1559
3835	KIF22	M2	Human	Breast	IDC	4.12e-03	3.30e-01	0.21
3835	KIF22	DCIS2	Human	Breast	DCIS	4.18e-27	7.54e-02	0.0085
3835	KIF22	HTA11_347_2000001011	Human	Colorectum	AD	6.48e-11	3.15e-01	-0.1954
3835	KIF22	HTA11_696_2000001011	Human	Colorectum	AD	7.10e-08	3.41e-01	-0.1464
3835	KIF22	HTA11_1391_2000001011	Human	Colorectum	AD	9.52e-03	2.28e-01	-0.059
3835	KIF22	LZE4T	Human	Esophagus	ESCC	1.56e-04	2.66e-01	0.0811

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
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
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
Stomach	WIM
Stomach	SIM
Liver	NAFLD
Liver	Cirrhotic
Liver	HCC

∗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:0051656	Colorectum	AD	establishment of organelle localization	131/3918	390/18723	3.00e-09	2.06e-07	131
GO:0007062	Colorectum	AD	sister chromatid cohesion	23/3918	62/18723	2.51e-03	1.92e-02	23
GO:0140014	Colorectum	AD	mitotic nuclear division	78/3918	287/18723	6.48e-03	4.05e-02	78
GO:005165616	Esophagus	HGIN	establishment of organelle localization	90/2587	390/18723	4.27e-07	1.94e-05	90
GO:00500003	Esophagus	HGIN	chromosome localization	24/2587	82/18723	2.07e-04	3.82e-03	24
GO:01400146	Esophagus	HGIN	mitotic nuclear division	61/2587	287/18723	3.38e-04	5.55e-03	61
GO:00070593	Esophagus	HGIN	chromosome segregation	71/2587	346/18723	3.47e-04	5.62e-03	71
GO:00513033	Esophagus	HGIN	establishment of chromosome localization	23/2587	80/18723	3.71e-04	5.77e-03	23
GO:00070803	Esophagus	HGIN	mitotic metaphase plate congression	15/2587	50/18723	2.35e-03	2.39e-02	15
GO:00513103	Esophagus	HGIN	metaphase plate congression	18/2587	65/18723	2.46e-03	2.45e-02	18
GO:00000703	Esophagus	HGIN	mitotic sister chromatid segregation	36/2587	168/18723	4.42e-03	3.87e-02	36
GO:014001414	Esophagus	ESCC	mitotic nuclear division	218/8552	287/18723	6.17e-26	1.78e-23	218
GO:005165617	Esophagus	ESCC	establishment of organelle localization	273/8552	390/18723	9.13e-23	1.81e-20	273
GO:000007011	Esophagus	ESCC	mitotic sister chromatid segregation	138/8552	168/18723	1.37e-22	2.63e-20	138
GO:00008194	Esophagus	ESCC	sister chromatid segregation	157/8552	202/18723	8.41e-21	1.33e-18	157
GO:000705911	Esophagus	ESCC	chromosome segregation	238/8552	346/18723	1.72e-18	1.82e-16	238
GO:005131011	Esophagus	ESCC	metaphase plate congression	58/8552	65/18723	1.81e-13	8.63e-12	58
GO:000708011	Esophagus	ESCC	mitotic metaphase plate congression	47/8552	50/18723	3.15e-13	1.47e-11	47
GO:00482853	Esophagus	ESCC	organelle fission	301/8552	488/18723	4.64e-13	2.12e-11	301
GO:00988133	Esophagus	ESCC	nuclear chromosome segregation	187/8552	281/18723	1.00e-12	4.36e-11	187

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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

KIF22

SNV

Missense_Mutation

rs775371597

c.689G>A

p.Arg230Gln

p.R230Q

Q14807

protein_coding

tolerated(0.64)

benign(0.003)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

KIF22

SNV

Missense_Mutation

c.341N>G

p.His114Arg

p.H114R

Q14807

protein_coding

deleterious(0.03)

possibly_damaging(0.451)

TCGA-BH-A0HA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

KIF22

SNV

Missense_Mutation

rs766845044

c.1334N>A

p.Ser445Asn

p.S445N

Q14807

protein_coding

tolerated(0.21)

benign(0.003)

TCGA-BH-A0HP-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

doxorubicin

KIF22

SNV

Missense_Mutation

c.1639N>A

p.Glu547Lys

p.E547K

Q14807

protein_coding

tolerated(0.51)

benign(0)

TCGA-D8-A1JD-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

KIF22

SNV

Missense_Mutation

novel

c.1938N>T

p.Glu646Asp

p.E646D

Q14807

protein_coding

tolerated(0.45)

benign(0.035)

TCGA-LL-A73Z-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

KIF22

insertion

Nonsense_Mutation

novel

c.154_155insACTTCCCCTTCCCCTTAGATTGATCA

p.Pro52HisfsTer8

p.P52Hfs*8

Q14807

protein_coding

TCGA-AO-A0JB-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

KIF22

SNV

Missense_Mutation

novel

c.1766G>A

p.Arg589His

p.R589H

Q14807

protein_coding

tolerated(0.07)

possibly_damaging(0.614)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

KIF22

SNV

Missense_Mutation

novel

c.1378N>G

p.Leu460Val

p.L460V

Q14807

protein_coding

tolerated(0.17)

benign(0.001)

TCGA-C5-A1MH-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

cisplatin

KIF22

SNV

Missense_Mutation

rs780221407

c.1208G>A

p.Arg403Gln

p.R403Q

Q14807

protein_coding

tolerated(0.17)

benign(0.01)

TCGA-EK-A2RB-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

KIF22

SNV

Missense_Mutation

c.1792N>C

p.Glu598Gln

p.E598Q

Q14807

protein_coding

tolerated(0.39)

benign(0.058)

TCGA-JW-A5VL-01

Cervix

cervical & endocervical cancer

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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