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: MLXIP

Gene summary for MLXIP

Gene summary.

Gene information	Species	Human
	Gene symbol	MLXIP
	Gene ID	22877
	Gene name	MLX interacting protein
	Gene Alias	MIR
	Cytomap	12q24.31
	Gene Type	protein-coding
	GO ID	GO:0006139
	UniProtAcc	Q9HAP2

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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
22877	MLXIP	HTA11_3410_2000001011	Human	Colorectum	AD	2.43e-13	6.30e-01	0.0155
22877	MLXIP	HTA11_2951_2000001011	Human	Colorectum	AD	9.74e-08	8.67e-01	0.0216
22877	MLXIP	HTA11_1938_2000001011	Human	Colorectum	AD	3.40e-10	6.98e-01	-0.0811
22877	MLXIP	HTA11_347_2000001011	Human	Colorectum	AD	1.56e-31	1.07e+00	-0.1954
22877	MLXIP	HTA11_3361_2000001011	Human	Colorectum	AD	1.22e-05	6.16e-01	-0.1207
22877	MLXIP	HTA11_83_2000001011	Human	Colorectum	SER	2.74e-09	8.92e-01	-0.1526
22877	MLXIP	HTA11_696_2000001011	Human	Colorectum	AD	2.51e-11	6.81e-01	-0.1464
22877	MLXIP	HTA11_866_2000001011	Human	Colorectum	AD	1.08e-05	4.82e-01	-0.1001
22877	MLXIP	HTA11_1391_2000001011	Human	Colorectum	AD	2.78e-03	5.33e-01	-0.059
22877	MLXIP	HTA11_2992_2000001011	Human	Colorectum	SER	3.60e-03	6.00e-01	-0.1706
22877	MLXIP	HTA11_5212_2000001011	Human	Colorectum	AD	1.47e-02	4.97e-01	-0.2061
22877	MLXIP	HTA11_5216_2000001011	Human	Colorectum	SER	4.67e-04	5.79e-01	-0.1462
22877	MLXIP	HTA11_546_2000001011	Human	Colorectum	AD	9.97e-15	1.02e+00	-0.0842
22877	MLXIP	HTA11_9341_2000001011	Human	Colorectum	SER	1.89e-02	4.64e-01	-0.00410000000000005
22877	MLXIP	HTA11_7862_2000001011	Human	Colorectum	AD	7.48e-15	8.46e-01	-0.0179
22877	MLXIP	HTA11_4255_2000001011	Human	Colorectum	SER	9.56e-04	6.16e-01	0.0446
22877	MLXIP	HTA11_9408_2000001011	Human	Colorectum	AD	2.77e-11	8.65e-01	0.0451
22877	MLXIP	HTA11_7663_2000001011	Human	Colorectum	SER	2.40e-14	1.19e+00	0.0131
22877	MLXIP	HTA11_10623_2000001011	Human	Colorectum	AD	1.07e-21	1.34e+00	-0.0177
22877	MLXIP	HTA11_6801_2000001011	Human	Colorectum	SER	1.24e-08	8.11e-01	0.0171

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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:000918512	Liver	Cirrhotic	ribonucleoside diphosphate metabolic process	52/4634	106/18723	5.24e-08	1.63e-06	52
GO:000974312	Liver	Cirrhotic	response to carbohydrate	101/4634	253/18723	6.24e-08	1.92e-06	101
GO:000913212	Liver	Cirrhotic	nucleoside diphosphate metabolic process	58/4634	124/18723	7.88e-08	2.33e-06	58
GO:000913512	Liver	Cirrhotic	purine nucleoside diphosphate metabolic process	50/4634	103/18723	1.43e-07	3.87e-06	50
GO:000917912	Liver	Cirrhotic	purine ribonucleoside diphosphate metabolic process	50/4634	103/18723	1.43e-07	3.87e-06	50
GO:004693912	Liver	Cirrhotic	nucleotide phosphorylation	49/4634	101/18723	1.95e-07	5.07e-06	49
GO:004603112	Liver	Cirrhotic	ADP metabolic process	45/4634	90/18723	2.01e-07	5.21e-06	45
GO:000663311	Liver	Cirrhotic	fatty acid biosynthetic process	70/4634	163/18723	2.57e-07	6.41e-06	70
GO:006201212	Liver	Cirrhotic	regulation of small molecule metabolic process	124/4634	334/18723	2.74e-07	6.79e-06	124
GO:003428412	Liver	Cirrhotic	response to monosaccharide	90/4634	225/18723	2.87e-07	7.01e-06	90
GO:000609012	Liver	Cirrhotic	pyruvate metabolic process	50/4634	106/18723	4.39e-07	1.02e-05	50
GO:004346712	Liver	Cirrhotic	regulation of generation of precursor metabolites and energy	58/4634	130/18723	5.81e-07	1.28e-05	58
GO:001605212	Liver	Cirrhotic	carbohydrate catabolic process	66/4634	154/18723	6.10e-07	1.32e-05	66
GO:000616512	Liver	Cirrhotic	nucleoside diphosphate phosphorylation	47/4634	99/18723	7.63e-07	1.61e-05	47
GO:004593612	Liver	Cirrhotic	negative regulation of phosphate metabolic process	154/4634	441/18723	8.78e-07	1.83e-05	154
GO:001056312	Liver	Cirrhotic	negative regulation of phosphorus metabolic process	154/4634	442/18723	1.02e-06	2.11e-05	154
GO:000974612	Liver	Cirrhotic	response to hexose	86/4634	219/18723	1.30e-06	2.59e-05	86
GO:001921611	Liver	Cirrhotic	regulation of lipid metabolic process	119/4634	331/18723	3.05e-06	5.39e-05	119
GO:004232612	Liver	Cirrhotic	negative regulation of phosphorylation	135/4634	385/18723	3.17e-06	5.58e-05	135
GO:000609612	Liver	Cirrhotic	glycolytic process	39/4634	81/18723	4.22e-06	7.06e-05	39

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa04932	Colorectum	AD	Non-alcoholic fatty liver disease	90/2092	155/8465	4.83e-19	1.80e-17	1.15e-17	90
hsa049321	Colorectum	AD	Non-alcoholic fatty liver disease	90/2092	155/8465	4.83e-19	1.80e-17	1.15e-17	90
hsa049322	Colorectum	SER	Non-alcoholic fatty liver disease	75/1580	155/8465	2.16e-17	5.99e-16	4.35e-16	75
hsa049323	Colorectum	SER	Non-alcoholic fatty liver disease	75/1580	155/8465	2.16e-17	5.99e-16	4.35e-16	75
hsa049324	Colorectum	MSS	Non-alcoholic fatty liver disease	85/1875	155/8465	4.19e-19	1.17e-17	7.17e-18	85
hsa04931	Colorectum	MSS	Insulin resistance	36/1875	108/8465	4.74e-03	2.01e-02	1.23e-02	36
hsa049325	Colorectum	MSS	Non-alcoholic fatty liver disease	85/1875	155/8465	4.19e-19	1.17e-17	7.17e-18	85
hsa049311	Colorectum	MSS	Insulin resistance	36/1875	108/8465	4.74e-03	2.01e-02	1.23e-02	36
hsa049326	Colorectum	MSI-H	Non-alcoholic fatty liver disease	52/797	155/8465	4.61e-17	1.49e-15	1.25e-15	52
hsa049327	Colorectum	MSI-H	Non-alcoholic fatty liver disease	52/797	155/8465	4.61e-17	1.49e-15	1.25e-15	52
hsa049328	Colorectum	FAP	Non-alcoholic fatty liver disease	54/1404	155/8465	1.98e-08	6.20e-07	3.77e-07	54
hsa049312	Colorectum	FAP	Insulin resistance	32/1404	108/8465	4.90e-04	3.56e-03	2.16e-03	32
hsa049329	Colorectum	FAP	Non-alcoholic fatty liver disease	54/1404	155/8465	1.98e-08	6.20e-07	3.77e-07	54
hsa049313	Colorectum	FAP	Insulin resistance	32/1404	108/8465	4.90e-04	3.56e-03	2.16e-03	32
hsa049314	Colorectum	CRC	Insulin resistance	28/1091	108/8465	1.78e-04	2.37e-03	1.61e-03	28
hsa049315	Colorectum	CRC	Insulin resistance	28/1091	108/8465	1.78e-04	2.37e-03	1.61e-03	28
hsa04932210	Esophagus	ESCC	Non-alcoholic fatty liver disease	122/4205	155/8465	5.69e-14	1.59e-12	8.14e-13	122
hsa049318	Esophagus	ESCC	Insulin resistance	69/4205	108/8465	1.92e-03	5.54e-03	2.84e-03	69
hsa0493238	Esophagus	ESCC	Non-alcoholic fatty liver disease	122/4205	155/8465	5.69e-14	1.59e-12	8.14e-13	122
hsa0493113	Esophagus	ESCC	Insulin resistance	69/4205	108/8465	1.92e-03	5.54e-03	2.84e-03	69

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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

TF	Cell Type	Tissue	Disease Stage	Target Gene	RSS	Regulon Activity
MLXIP	CAF	Breast	ADJ	NEAT1,KRT6B,SOX9, etc.	9.09e-02
MLXIP	BAS	Cervix	Healthy	KRAS,NAPB,PICALM, etc.	2.72e-01
MLXIP	ABS	Colorectum	FAP	SELENBP1,ADAMTSL1,AC103702.2, etc.	1.76e-01
MLXIP	DUCT2	Pancreas	ADJ	NTN4,ZNF335,UBR1, etc.	4.05e-03

∗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

MLXIP

SNV

Missense_Mutation

rs528028662

c.2651C>T

p.Thr884Met

p.T884M

Q9HAP2

protein_coding

deleterious(0)

probably_damaging(0.953)

TCGA-A2-A0T1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Targeted Molecular therapy

herceptin

MLXIP

SNV

Missense_Mutation

novel

c.727N>G

p.Ser243Gly

p.S243G

Q9HAP2

protein_coding

deleterious(0.01)

possibly_damaging(0.852)

TCGA-BH-A0AY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

MLXIP

SNV

Missense_Mutation

c.374C>G

p.Ser125Trp

p.S125W

Q9HAP2

protein_coding

deleterious(0)

probably_damaging(0.942)

TCGA-D8-A1JA-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

MLXIP

SNV

Missense_Mutation

c.225N>C

p.Gln75His

p.Q75H

Q9HAP2

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-E2-A159-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

MLXIP

SNV

Missense_Mutation

rs202216030

c.2362N>A

p.Glu788Lys

p.E788K

Q9HAP2

protein_coding

deleterious(0)

probably_damaging(0.99)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

MLXIP

SNV

Missense_Mutation

novel

c.2709N>T

p.Glu903Asp

p.E903D

Q9HAP2

protein_coding

tolerated(0.07)

possibly_damaging(0.53)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

MLXIP

SNV

Missense_Mutation

c.1480N>T

p.His494Tyr

p.H494Y

Q9HAP2

protein_coding

tolerated(0.06)

possibly_damaging(0.899)

TCGA-C5-A3HL-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

MLXIP

SNV

Missense_Mutation

novel

c.1159N>T

p.Thr387Ser

p.T387S

Q9HAP2

protein_coding

tolerated(0.59)

benign(0.009)

TCGA-DS-A1OA-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

carboplatin

MLXIP

SNV

Missense_Mutation

c.2131C>T

p.Pro711Ser

p.P711S

Q9HAP2

protein_coding

tolerated(0.32)

benign(0.001)

TCGA-AA-3492-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

MLXIP

SNV

Missense_Mutation

c.901N>T

p.Arg301Trp

p.R301W

Q9HAP2

protein_coding

deleterious(0)

probably_damaging(0.982)

TCGA-AD-5900-01

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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