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: IVD

Gene summary for IVD

Gene summary.

Gene information	Species	Human
	Gene symbol	IVD
	Gene ID	3712
	Gene name	isovaleryl-CoA dehydrogenase
	Gene Alias	ACAD2
	Cytomap	15q15.1
	Gene Type	protein-coding
	GO ID	GO:0006082
	UniProtAcc	P26440

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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
3712	IVD	HTA11_347_2000001011	Human	Colorectum	AD	4.28e-06	4.15e-01	-0.1954
3712	IVD	HTA11_1391_2000001011	Human	Colorectum	AD	6.24e-03	4.86e-01	-0.059
3712	IVD	HTA11_7696_3000711011	Human	Colorectum	AD	1.59e-04	3.83e-01	0.0674
3712	IVD	HTA11_99999965104_69814	Human	Colorectum	MSS	1.56e-03	3.13e-01	0.281
3712	IVD	F007	Human	Colorectum	FAP	2.24e-02	-2.39e-01	0.1176
3712	IVD	A015-C-203	Human	Colorectum	FAP	5.08e-06	-1.23e-01	-0.1294
3712	IVD	A002-C-201	Human	Colorectum	FAP	7.83e-03	-1.54e-01	0.0324
3712	IVD	A001-C-108	Human	Colorectum	FAP	8.30e-04	-1.17e-01	-0.0272
3712	IVD	A002-C-205	Human	Colorectum	FAP	1.24e-03	-1.22e-01	-0.1236
3712	IVD	A015-C-006	Human	Colorectum	FAP	2.96e-02	-3.59e-02	-0.0994
3712	IVD	A002-C-114	Human	Colorectum	FAP	4.57e-03	-1.04e-01	-0.1561
3712	IVD	A015-C-104	Human	Colorectum	FAP	1.29e-07	-1.21e-01	-0.1899
3712	IVD	A001-C-014	Human	Colorectum	FAP	2.20e-02	-1.57e-01	0.0135
3712	IVD	A002-C-016	Human	Colorectum	FAP	1.57e-05	-1.62e-01	0.0521
3712	IVD	A002-C-116	Human	Colorectum	FAP	3.87e-08	-1.73e-01	-0.0452
3712	IVD	A018-E-020	Human	Colorectum	FAP	4.23e-04	-1.67e-01	-0.2034
3712	IVD	F034	Human	Colorectum	FAP	7.70e-04	-1.27e-01	-0.0665
3712	IVD	CRC-3-11773	Human	Colorectum	CRC	1.94e-03	-1.49e-01	0.2564
3712	IVD	LZE2T	Human	Esophagus	ESCC	1.02e-06	5.15e-01	0.082
3712	IVD	LZE4T	Human	Esophagus	ESCC	1.62e-11	3.68e-01	0.0811

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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
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:0044282	Colorectum	AD	small molecule catabolic process	118/3918	376/18723	1.05e-06	3.55e-05	118
GO:0006635	Colorectum	AD	fatty acid beta-oxidation	33/3918	74/18723	3.98e-06	1.09e-04	33
GO:0009062	Colorectum	AD	fatty acid catabolic process	41/3918	100/18723	4.02e-06	1.09e-04	41
GO:0019395	Colorectum	AD	fatty acid oxidation	40/3918	103/18723	2.43e-05	4.69e-04	40
GO:0016042	Colorectum	AD	lipid catabolic process	97/3918	320/18723	4.31e-05	7.56e-04	97
GO:0006631	Colorectum	AD	fatty acid metabolic process	114/3918	390/18723	5.58e-05	9.44e-04	114
GO:0072329	Colorectum	AD	monocarboxylic acid catabolic process	44/3918	122/18723	8.05e-05	1.28e-03	44
GO:0034440	Colorectum	AD	lipid oxidation	40/3918	108/18723	8.52e-05	1.32e-03	40
GO:0030258	Colorectum	AD	lipid modification	67/3918	212/18723	1.66e-04	2.27e-03	67
GO:0009083	Colorectum	AD	branched-chain amino acid catabolic process	10/3918	15/18723	1.68e-04	2.29e-03	10
GO:0016054	Colorectum	AD	organic acid catabolic process	73/3918	240/18723	3.20e-04	3.81e-03	73
GO:0044242	Colorectum	AD	cellular lipid catabolic process	66/3918	214/18723	3.96e-04	4.50e-03	66
GO:0046395	Colorectum	AD	carboxylic acid catabolic process	70/3918	236/18723	9.06e-04	8.71e-03	70
GO:0006520	Colorectum	AD	cellular amino acid metabolic process	81/3918	284/18723	1.37e-03	1.19e-02	81
GO:0009081	Colorectum	AD	branched-chain amino acid metabolic process	10/3918	19/18723	2.25e-03	1.77e-02	10
GO:00090831	Colorectum	MSS	branched-chain amino acid catabolic process	10/3467	15/18723	5.64e-05	9.87e-04	10
GO:00090622	Colorectum	MSS	fatty acid catabolic process	32/3467	100/18723	8.28e-04	8.67e-03	32
GO:00090811	Colorectum	MSS	branched-chain amino acid metabolic process	10/3467	19/18723	8.39e-04	8.68e-03	10
GO:00442822	Colorectum	MSS	small molecule catabolic process	94/3467	376/18723	9.85e-04	9.86e-03	94
GO:00302582	Colorectum	MSS	lipid modification	57/3467	212/18723	1.64e-03	1.49e-02	57

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa00280	Colorectum	AD	Valine, leucine and isoleucine degradation	25/2092	48/8465	3.97e-05	3.41e-04	2.18e-04	25
hsa002801	Colorectum	AD	Valine, leucine and isoleucine degradation	25/2092	48/8465	3.97e-05	3.41e-04	2.18e-04	25
hsa002802	Colorectum	MSS	Valine, leucine and isoleucine degradation	21/1875	48/8465	6.73e-04	4.51e-03	2.76e-03	21
hsa002803	Colorectum	MSS	Valine, leucine and isoleucine degradation	21/1875	48/8465	6.73e-04	4.51e-03	2.76e-03	21
hsa002804	Colorectum	FAP	Valine, leucine and isoleucine degradation	18/1404	48/8465	3.94e-04	3.06e-03	1.86e-03	18
hsa002805	Colorectum	FAP	Valine, leucine and isoleucine degradation	18/1404	48/8465	3.94e-04	3.06e-03	1.86e-03	18
hsa002809	Esophagus	ESCC	Valine, leucine and isoleucine degradation	34/4205	48/8465	2.34e-03	6.54e-03	3.35e-03	34
hsa0028014	Esophagus	ESCC	Valine, leucine and isoleucine degradation	34/4205	48/8465	2.34e-03	6.54e-03	3.35e-03	34
hsa002806	Liver	NAFLD	Valine, leucine and isoleucine degradation	20/1043	48/8465	3.03e-07	1.65e-05	1.33e-05	20
hsa0028011	Liver	NAFLD	Valine, leucine and isoleucine degradation	20/1043	48/8465	3.03e-07	1.65e-05	1.33e-05	20
hsa0028021	Liver	Cirrhotic	Valine, leucine and isoleucine degradation	32/2530	48/8465	1.45e-07	2.02e-06	1.24e-06	32
hsa0028031	Liver	Cirrhotic	Valine, leucine and isoleucine degradation	32/2530	48/8465	1.45e-07	2.02e-06	1.24e-06	32
hsa0028041	Liver	HCC	Valine, leucine and isoleucine degradation	41/4020	48/8465	4.84e-08	7.05e-07	3.92e-07	41
hsa0028051	Liver	HCC	Valine, leucine and isoleucine degradation	41/4020	48/8465	4.84e-08	7.05e-07	3.92e-07	41
hsa002808	Oral cavity	OSCC	Valine, leucine and isoleucine degradation	30/3704	48/8465	6.75e-03	1.57e-02	7.99e-03	30
hsa0028013	Oral cavity	OSCC	Valine, leucine and isoleucine degradation	30/3704	48/8465	6.75e-03	1.57e-02	7.99e-03	30
hsa002807	Prostate	Tumor	Valine, leucine and isoleucine degradation	20/1791	48/8465	1.03e-03	4.59e-03	2.84e-03	20
hsa0028012	Prostate	Tumor	Valine, leucine and isoleucine degradation	20/1791	48/8465	1.03e-03	4.59e-03	2.84e-03	20

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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

IVD

SNV

Missense_Mutation

rs189587579

c.47C>T

p.Ala16Val

p.A16V

protein_coding

tolerated_low_confidence(0.07)

benign(0.001)

TCGA-A2-A0YJ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cytoxan

IVD

SNV

Missense_Mutation

c.1193G>A

p.Arg398Gln

p.R398Q

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

IVD

SNV

Missense_Mutation

novel

c.54N>C

p.Trp18Cys

p.W18C

protein_coding

tolerated_low_confidence(0.15)

benign(0.012)

TCGA-EW-A6SD-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

tch

IVD

insertion

In_Frame_Ins

novel

c.352_353insGTGGCCAGATGATGTGTT

p.Ile118delinsSerGlyGlnMetMetCysLeu

p.I118delinsSGQMMCL

protein_coding

TCGA-AO-A0JB-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

IVD

insertion

Frame_Shift_Ins

novel

c.354_355insATAGGCTG

p.Ser119IlefsTer41

p.S119Ifs*41

protein_coding

TCGA-AO-A0JB-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

IVD

SNV

Missense_Mutation

c.793G>A

p.Ala265Thr

p.A265T

protein_coding

tolerated(0.19)

benign(0.14)

TCGA-AA-3844-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Chemotherapy

capecitabine

IVD

SNV

Missense_Mutation

novel

c.1055N>G

p.Glu352Gly

p.E352G

protein_coding

deleterious(0.05)

benign(0.054)

TCGA-AU-6004-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

IVD

SNV

Missense_Mutation

rs755368630

c.217N>T

p.Arg73Cys

p.R73C

protein_coding

deleterious(0)

possibly_damaging(0.632)

TCGA-F5-6464-01

Colorectum

rectum adenocarcinoma

Female

>=65

III/IV

Unknown

IVD

SNV

Missense_Mutation

novel

c.396N>A

p.His132Gln

p.H132Q

protein_coding

deleterious(0)

probably_damaging(0.981)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

IVD

SNV

Missense_Mutation

novel

c.1036N>T

p.Val346Phe

p.V346F

protein_coding

deleterious(0)

probably_damaging(0.991)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

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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