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: ISCU

Gene summary for ISCU

Gene summary.

Gene information	Species	Human
	Gene symbol	ISCU
	Gene ID	23479
	Gene name	iron-sulfur cluster assembly enzyme
	Gene Alias	2310020H20Rik
	Cytomap	12q23.3
	Gene Type	protein-coding
	GO ID	GO:0000041
	UniProtAcc	B3KQ30

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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
23479	ISCU	HTA11_3410_2000001011	Human	Colorectum	AD	2.65e-09	3.05e-01	0.0155
23479	ISCU	HTA11_2487_2000001011	Human	Colorectum	SER	2.48e-04	3.85e-01	-0.1808
23479	ISCU	HTA11_1938_2000001011	Human	Colorectum	AD	9.41e-11	6.12e-01	-0.0811
23479	ISCU	HTA11_78_2000001011	Human	Colorectum	AD	7.92e-06	3.54e-01	-0.1088
23479	ISCU	HTA11_347_2000001011	Human	Colorectum	AD	2.83e-23	5.99e-01	-0.1954
23479	ISCU	HTA11_411_2000001011	Human	Colorectum	SER	2.37e-07	9.83e-01	-0.2602
23479	ISCU	HTA11_83_2000001011	Human	Colorectum	SER	4.03e-05	3.91e-01	-0.1526
23479	ISCU	HTA11_696_2000001011	Human	Colorectum	AD	1.52e-11	3.91e-01	-0.1464
23479	ISCU	HTA11_866_2000001011	Human	Colorectum	AD	1.15e-06	3.03e-01	-0.1001
23479	ISCU	HTA11_1391_2000001011	Human	Colorectum	AD	1.86e-17	7.25e-01	-0.059
23479	ISCU	HTA11_2992_2000001011	Human	Colorectum	SER	1.40e-02	5.03e-01	-0.1706
23479	ISCU	HTA11_5212_2000001011	Human	Colorectum	AD	1.55e-06	4.87e-01	-0.2061
23479	ISCU	HTA11_7862_2000001011	Human	Colorectum	AD	3.23e-06	4.35e-01	-0.0179
23479	ISCU	HTA11_866_3004761011	Human	Colorectum	AD	2.13e-15	4.87e-01	0.096
23479	ISCU	HTA11_4255_2000001011	Human	Colorectum	SER	3.93e-05	4.52e-01	0.0446
23479	ISCU	HTA11_8622_2000001021	Human	Colorectum	SER	4.07e-08	5.78e-01	0.0528
23479	ISCU	HTA11_7663_2000001011	Human	Colorectum	SER	1.61e-05	6.42e-01	0.0131
23479	ISCU	HTA11_10623_2000001011	Human	Colorectum	AD	2.47e-02	2.90e-01	-0.0177
23479	ISCU	HTA11_6801_2000001011	Human	Colorectum	SER	5.92e-06	6.52e-01	0.0171
23479	ISCU	HTA11_10711_2000001011	Human	Colorectum	AD	2.16e-02	2.91e-01	0.0338

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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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid 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
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:0046034	Colorectum	AD	ATP metabolic process	142/3918	277/18723	2.64e-29	8.26e-26	142
GO:0006091	Colorectum	AD	generation of precursor metabolites and energy	209/3918	490/18723	3.17e-28	6.61e-25	209
GO:0009060	Colorectum	AD	aerobic respiration	108/3918	189/18723	9.14e-28	1.43e-24	108
GO:0045333	Colorectum	AD	cellular respiration	119/3918	230/18723	3.21e-25	4.02e-22	119
GO:0006119	Colorectum	AD	oxidative phosphorylation	83/3918	141/18723	7.95e-23	8.30e-20	83
GO:0015980	Colorectum	AD	energy derivation by oxidation of organic compounds	143/3918	318/18723	2.78e-22	2.49e-19	143
GO:0022900	Colorectum	AD	electron transport chain	89/3918	175/18723	1.42e-18	8.91e-16	89
GO:0019646	Colorectum	AD	aerobic electron transport chain	53/3918	87/18723	5.58e-16	2.16e-13	53
GO:0042773	Colorectum	AD	ATP synthesis coupled electron transport	56/3918	95/18723	6.76e-16	2.22e-13	56
GO:0042775	Colorectum	AD	mitochondrial ATP synthesis coupled electron transport	56/3918	95/18723	6.76e-16	2.22e-13	56
GO:0022904	Colorectum	AD	respiratory electron transport chain	63/3918	114/18723	8.23e-16	2.45e-13	63
GO:0006120	Colorectum	AD	mitochondrial electron transport, NADH to ubiquinone	32/3918	51/18723	1.12e-10	1.11e-08	32
GO:0055076	Colorectum	AD	transition metal ion homeostasis	53/3918	138/18723	1.89e-06	5.65e-05	53
GO:0043467	Colorectum	AD	regulation of generation of precursor metabolites and energy	49/3918	130/18723	8.33e-06	1.99e-04	49
GO:0046916	Colorectum	AD	cellular transition metal ion homeostasis	43/3918	115/18723	3.62e-05	6.56e-04	43
GO:0006790	Colorectum	AD	sulfur compound metabolic process	101/3918	339/18723	6.46e-05	1.07e-03	101
GO:0055072	Colorectum	AD	iron ion homeostasis	32/3918	85/18723	2.97e-04	3.60e-03	32
GO:0043457	Colorectum	AD	regulation of cellular respiration	20/3918	49/18723	1.23e-03	1.09e-02	20
GO:1903715	Colorectum	AD	regulation of aerobic respiration	15/3918	33/18723	1.36e-03	1.18e-02	15
GO:0006879	Colorectum	AD	cellular iron ion homeostasis	25/3918	67/18723	1.51e-03	1.27e-02	25

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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

ISCU

insertion

Frame_Shift_Ins

novel

c.209_210insACCATTCAAGAGAAAAATCCATTTCCCAGATTCCTCCCCTTTA

p.Asp71ProfsTer15

p.D71Pfs*15

Q9H1K1

protein_coding

TCGA-B6-A0IA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ISCU

SNV

Missense_Mutation

c.214N>A

p.Val72Ile

p.V72I

Q9H1K1

protein_coding

deleterious_low_confidence(0.01)

possibly_damaging(0.88)

TCGA-AA-A017-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

ISCU

SNV

Missense_Mutation

novel

c.278T>G

p.Phe93Cys

p.F93C

Q9H1K1

protein_coding

deleterious_low_confidence(0)

probably_damaging(1)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

ISCU

SNV

Missense_Mutation

rs371513074

c.145N>A

p.Val49Met

p.V49M

Q9H1K1

protein_coding

deleterious_low_confidence(0.01)

probably_damaging(0.956)

TCGA-AJ-A3BG-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Chemotherapy

carboplatin

ISCU

SNV

Missense_Mutation

c.421N>A

p.Leu141Met

p.L141M

Q9H1K1

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-D1-A103-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

ISCU

SNV

Missense_Mutation

novel

c.394N>T

p.Pro132Ser

p.P132S

Q9H1K1

protein_coding

deleterious_low_confidence(0)

probably_damaging(1)

TCGA-DF-A2KU-01

Endometrium

uterine corpus endometrioid carcinoma

Female

Unknown

I/II

Unknown

ISCU

SNV

Missense_Mutation

novel

c.398C>T

p.Pro133Leu

p.P133L

Q9H1K1

protein_coding

deleterious_low_confidence(0)

probably_damaging(1)

TCGA-EC-A24G-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

ISCU

SNV

Missense_Mutation

novel

c.358N>T

p.Ile120Phe

p.I120F

Q9H1K1

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.981)

TCGA-DD-AAW1-01

Liver

liver hepatocellular carcinoma

Male

<65

III/IV

Unknown

ISCU

SNV

Missense_Mutation

c.241N>A

p.Glu81Lys

p.E81K

Q9H1K1

protein_coding

tolerated_low_confidence(0.06)

benign(0.052)

TCGA-05-4395-01

Lung

lung adenocarcinoma

Male

>=65

III/IV

Unknown

ISCU

insertion

In_Frame_Ins

rs763609964

c.228_228+1insATTCAA

p.Ile77_Gln78dup

p.I77_Q78dup

Q9H1K1

protein_coding

TCGA-CV-7245-01

Oral cavity

head & neck squamous cell carcinoma

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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