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: MKKS

Gene summary for MKKS

Gene summary.

Gene information	Species	Human
	Gene symbol	MKKS
	Gene ID	8195
	Gene name	MKKS centrosomal shuttling protein
	Gene Alias	BBS6
	Cytomap	20p12.2
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	B7Z3W9

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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
8195	MKKS	HTA11_1938_2000001011	Human	Colorectum	AD	2.33e-08	3.93e-01	-0.0811
8195	MKKS	HTA11_78_2000001011	Human	Colorectum	AD	7.66e-04	2.72e-01	-0.1088
8195	MKKS	HTA11_347_2000001011	Human	Colorectum	AD	2.29e-25	5.88e-01	-0.1954
8195	MKKS	HTA11_1391_2000001011	Human	Colorectum	AD	3.51e-11	4.02e-01	-0.059
8195	MKKS	HTA11_866_3004761011	Human	Colorectum	AD	6.27e-06	2.69e-01	0.096
8195	MKKS	HTA11_7663_2000001011	Human	Colorectum	SER	2.57e-02	4.12e-01	0.0131
8195	MKKS	HTA11_10623_2000001011	Human	Colorectum	AD	2.78e-02	3.17e-01	-0.0177
8195	MKKS	HTA11_99999970781_79442	Human	Colorectum	MSS	1.35e-05	2.91e-01	0.294
8195	MKKS	HTA11_99999965104_69814	Human	Colorectum	MSS	1.29e-08	5.28e-01	0.281
8195	MKKS	HTA11_99999971662_82457	Human	Colorectum	MSS	2.11e-03	2.69e-01	0.3859
8195	MKKS	A015-C-203	Human	Colorectum	FAP	3.61e-02	-8.65e-02	-0.1294
8195	MKKS	LZE2T	Human	Esophagus	ESCC	1.25e-05	1.33e+00	0.082
8195	MKKS	LZE4T	Human	Esophagus	ESCC	1.00e-14	6.27e-01	0.0811
8195	MKKS	LZE7T	Human	Esophagus	ESCC	4.31e-04	5.09e-01	0.0667
8195	MKKS	LZE8T	Human	Esophagus	ESCC	7.11e-05	2.70e-01	0.067
8195	MKKS	LZE22D1	Human	Esophagus	HGIN	3.13e-02	7.35e-02	0.0595
8195	MKKS	LZE24T	Human	Esophagus	ESCC	2.44e-06	3.54e-01	0.0596
8195	MKKS	LZE6T	Human	Esophagus	ESCC	6.87e-10	7.70e-01	0.0845
8195	MKKS	P1T-E	Human	Esophagus	ESCC	2.21e-10	8.14e-01	0.0875
8195	MKKS	P2T-E	Human	Esophagus	ESCC	1.43e-32	6.97e-01	0.1177

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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:0021543	Colorectum	FAP	pallium development	36/2622	169/18723	6.06e-03	3.81e-02	36
GO:0014829	Colorectum	FAP	vascular associated smooth muscle contraction	9/2622	26/18723	6.73e-03	4.14e-02	9
GO:0040014	Colorectum	FAP	regulation of multicellular organism growth	16/2622	61/18723	8.38e-03	4.89e-02	16
GO:0030900	Colorectum	FAP	forebrain development	70/2622	379/18723	8.64e-03	4.98e-02	70
GO:000645720	Esophagus	HGIN	protein folding	75/2587	212/18723	1.61e-15	3.86e-13	75
GO:005165616	Esophagus	HGIN	establishment of organelle localization	90/2587	390/18723	4.27e-07	1.94e-05	90
GO:004325427	Esophagus	HGIN	regulation of protein-containing complex assembly	94/2587	428/18723	2.39e-06	8.55e-05	94
GO:001063920	Esophagus	HGIN	negative regulation of organelle organization	79/2587	348/18723	4.12e-06	1.37e-04	79
GO:005125826	Esophagus	HGIN	protein polymerization	66/2587	297/18723	4.96e-05	1.19e-03	66
GO:190290327	Esophagus	HGIN	regulation of supramolecular fiber organization	79/2587	383/18723	1.40e-04	2.81e-03	79
GO:005113118	Esophagus	HGIN	chaperone-mediated protein complex assembly	10/2587	23/18723	5.09e-04	7.38e-03	10
GO:003297027	Esophagus	HGIN	regulation of actin filament-based process	77/2587	397/18723	1.14e-03	1.39e-02	77
GO:003166726	Esophagus	HGIN	response to nutrient levels	89/2587	474/18723	1.41e-03	1.64e-02	89
GO:003227126	Esophagus	HGIN	regulation of protein polymerization	49/2587	233/18723	1.56e-03	1.79e-02	49
GO:003295627	Esophagus	HGIN	regulation of actin cytoskeleton organization	69/2587	358/18723	2.35e-03	2.39e-02	69
GO:003133320	Esophagus	HGIN	negative regulation of protein-containing complex assembly	32/2587	141/18723	2.80e-03	2.74e-02	32
GO:005134620	Esophagus	HGIN	negative regulation of hydrolase activity	72/2587	379/18723	2.81e-03	2.75e-02	72
GO:005165010	Esophagus	HGIN	establishment of vesicle localization	35/2587	161/18723	3.89e-03	3.54e-02	35
GO:003004120	Esophagus	HGIN	actin filament polymerization	40/2587	191/18723	4.29e-03	3.82e-02	40
GO:006145819	Esophagus	HGIN	reproductive system development	78/2587	427/18723	5.53e-03	4.52e-02	78

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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

MKKS

SNV

Missense_Mutation

c.1133G>T

p.Arg378Ile

p.R378I

Q9NPJ1

protein_coding

deleterious(0)

possibly_damaging(0.902)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MKKS

SNV

Missense_Mutation

c.1045G>T

p.Asp349Tyr

p.D349Y

Q9NPJ1

protein_coding

deleterious(0)

probably_damaging(0.948)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MKKS

SNV

Missense_Mutation

novel

c.503G>A

p.Arg168Lys

p.R168K

Q9NPJ1

protein_coding

tolerated(0.89)

benign(0.001)

TCGA-AC-A5XS-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

femara

MKKS

SNV

Missense_Mutation

novel

c.8N>A

p.Arg3His

p.R3H

Q9NPJ1

protein_coding

deleterious(0.02)

probably_damaging(0.964)

TCGA-AO-A03L-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

MKKS

SNV

Missense_Mutation

novel

c.1615N>A

p.Leu539Met

p.L539M

Q9NPJ1

protein_coding

deleterious(0)

probably_damaging(0.934)

TCGA-LL-A441-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

MKKS

insertion

In_Frame_Ins

novel

c.22_23insTCAACTGCCCTCAAGGTGGCACTCTTTTGTACAACTTTATCC

p.Lys8delinsIleAsnCysProGlnGlyGlyThrLeuLeuTyrAsnPheIleGln

p.K8delinsINCPQGGTLLYNFIQ

Q9NPJ1

protein_coding

TCGA-B6-A0I5-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

MKKS

SNV

Missense_Mutation

novel

c.1166N>T

p.Thr389Met

p.T389M

Q9NPJ1

protein_coding

deleterious(0.01)

possibly_damaging(0.88)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

MKKS

SNV

Missense_Mutation

novel

c.173N>T

p.Ser58Leu

p.S58L

Q9NPJ1

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-HM-A4S6-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Chemotherapy

cisplatin

MKKS

SNV

Missense_Mutation

c.631G>T

p.Asp211Tyr

p.D211Y

Q9NPJ1

protein_coding

deleterious(0)

probably_damaging(0.98)

TCGA-AA-A010-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Chemotherapy

folinic

MKKS

SNV

Missense_Mutation

rs750058438

c.235N>A

p.Ala79Thr

p.A79T

Q9NPJ1

protein_coding

tolerated(0.84)

benign(0.01)

TCGA-CA-6717-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Chemotherapy

oxaliplatin

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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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