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: MAK

Gene summary for MAK

Gene summary.

Gene information	Species	Human
	Gene symbol	MAK
	Gene ID	4117
	Gene name	male germ cell associated kinase
	Gene Alias	RP62
	Cytomap	6p24.2
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	P20794

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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
4117	MAK	RNA-P17T-P17T-8	Human	Lung	IAC	1.77e-07	6.74e-01	0.3329
4117	MAK	RNA-P6T1-P6T1-3	Human	Lung	MIAC	3.47e-02	5.64e-01	-0.0296
4117	MAK	RNA-P6T1-P6T1-4	Human	Lung	MIAC	5.54e-03	4.83e-01	-0.0263

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma

∗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:00467776	Lung	IAC	protein autophosphorylation	51/2061	227/18723	4.85e-07	3.10e-05	51
GO:00106398	Lung	IAC	negative regulation of organelle organization	68/2061	348/18723	1.69e-06	8.24e-05	68
GO:00313455	Lung	IAC	negative regulation of cell projection organization	41/2061	186/18723	1.01e-05	3.23e-04	41
GO:01200327	Lung	IAC	regulation of plasma membrane bounded cell projection assembly	39/2061	186/18723	5.41e-05	1.21e-03	39
GO:00604916	Lung	IAC	regulation of cell projection assembly	39/2061	188/18723	6.92e-05	1.47e-03	39
GO:00307056	Lung	IAC	cytoskeleton-dependent intracellular transport	40/2061	195/18723	7.30e-05	1.54e-03	40
GO:1902855	Lung	IAC	regulation of non-motile cilium assembly	6/2061	10/18723	2.50e-04	4.23e-03	6
GO:19021152	Lung	IAC	regulation of organelle assembly	37/2061	186/18723	2.55e-04	4.26e-03	37
GO:00315032	Lung	IAC	protein-containing complex localization	42/2061	220/18723	2.60e-04	4.32e-03	42
GO:1905515	Lung	IAC	non-motile cilium assembly	16/2061	61/18723	7.09e-04	9.50e-03	16
GO:00018947	Lung	IAC	tissue homeostasis	46/2061	268/18723	1.50e-03	1.60e-02	46
GO:0099111	Lung	IAC	microtubule-based transport	35/2061	190/18723	1.55e-03	1.64e-02	35
GO:0060271	Lung	IAC	cilium assembly	55/2061	337/18723	1.84e-03	1.88e-02	55
GO:0120033	Lung	IAC	negative regulation of plasma membrane bounded cell projection assembly	10/2061	33/18723	2.18e-03	2.15e-02	10
GO:00602497	Lung	IAC	anatomical structure homeostasis	51/2061	314/18723	2.91e-03	2.61e-02	51
GO:0044782	Lung	IAC	cilium organization	58/2061	368/18723	3.15e-03	2.75e-02	58
GO:00109704	Lung	IAC	transport along microtubule	28/2061	155/18723	5.72e-03	4.18e-02	28
GO:00602711	Lung	MIAC	cilium assembly	37/967	337/18723	1.29e-05	9.85e-04	37
GO:00447821	Lung	MIAC	cilium organization	38/967	368/18723	3.93e-05	2.08e-03	38
GO:004677721	Lung	MIAC	protein autophosphorylation	27/967	227/18723	4.74e-05	2.46e-03	27

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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

MAK

SNV

Missense_Mutation

rs765357899

c.1098N>C

p.Lys366Asn

p.K366N

P20794

protein_coding

deleterious(0.03)

possibly_damaging(0.667)

TCGA-A8-A097-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

MAK

SNV

Missense_Mutation

c.745C>G

p.Leu249Val

p.L249V

P20794

protein_coding

tolerated(0.06)

possibly_damaging(0.551)

TCGA-BH-A0AW-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

MAK

SNV

Missense_Mutation

novel

c.1514A>C

p.Asn505Thr

p.N505T

P20794

protein_coding

tolerated(0.61)

benign(0.098)

TCGA-D8-A27N-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

taxol+adriamycin+cyclophosphamide+herceptin

MAK

deletion

In_Frame_Del

novel

c.1884_1889delACAGCC

p.Gln629_Pro630del

p.Q629_P630del

P20794

protein_coding

TCGA-A2-A0T0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

MAK

insertion

In_Frame_Ins

novel

c.910_911insCCTCCCAGGTTCAAGCAGTTCTCTTGCCTCAGCTTCCTG

p.Asn304delinsThrSerGlnValGlnAlaValLeuLeuProGlnLeuProAsp

p.N304delinsTSQVQAVLLPQLPD

P20794

protein_coding

TCGA-A8-A07J-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

MAK

insertion

Frame_Shift_Ins

novel

c.7_8insAGGAG

p.Arg3GlnfsTer7

p.R3Qfs*7

P20794

protein_coding

TCGA-A8-A07R-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Ancillary

zoledronic

MAK

insertion

Nonsense_Mutation

novel

c.6_7insTTAGCCAGGCATGGTGGCACGCGCCTGTAATCCCAGCTACT

p.Arg3LeufsTer10

p.R3Lfs*10

P20794

protein_coding

TCGA-A8-A07R-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Ancillary

zoledronic

MAK

SNV

Missense_Mutation

c.505N>A

p.Glu169Lys

p.E169K

P20794

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-MY-A5BE-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

MAK

SNV

Missense_Mutation

c.38N>A

p.Gly13Asp

p.G13D

P20794

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AA-3713-01

Colorectum

colon adenocarcinoma

Male

>=65

III/IV

Chemotherapy

5-fluorouracil

MAK

SNV

Missense_Mutation

rs764870230

c.1315C>T

p.Arg439Trp

p.R439W

P20794

protein_coding

deleterious(0.02)

possibly_damaging(0.764)

TCGA-AA-A00N-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

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