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: INPPL1

Gene summary for INPPL1

Gene summary.

Gene information	Species	Human
	Gene symbol	INPPL1
	Gene ID	3636
	Gene name	inositol polyphosphate phosphatase like 1
	Gene Alias	OPSMD
	Cytomap	11q13.4
	Gene Type	protein-coding
	GO ID	GO:0001501
	UniProtAcc	O15357

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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
3636	INPPL1	HTA11_2487_2000001011	Human	Colorectum	SER	9.40e-03	1.30e-01	-0.1808
3636	INPPL1	HTA11_347_2000001011	Human	Colorectum	AD	9.37e-13	2.70e-01	-0.1954
3636	INPPL1	HTA11_1391_2000001011	Human	Colorectum	AD	6.75e-07	3.34e-01	-0.059
3636	INPPL1	HTA11_866_3004761011	Human	Colorectum	AD	2.79e-08	3.17e-01	0.096
3636	INPPL1	HTA11_99999970781_79442	Human	Colorectum	MSS	9.30e-12	4.65e-01	0.294
3636	INPPL1	HTA11_99999971662_82457	Human	Colorectum	MSS	5.25e-10	5.32e-01	0.3859
3636	INPPL1	HTA11_99999973899_84307	Human	Colorectum	MSS	4.69e-02	3.21e-01	0.2585
3636	INPPL1	HTA11_99999974143_84620	Human	Colorectum	MSS	4.84e-02	2.83e-01	0.3005
3636	INPPL1	CRC-3-11773	Human	Colorectum	CRC	5.12e-06	4.59e-01	0.2564
3636	INPPL1	LZE7T	Human	Esophagus	ESCC	2.52e-03	1.77e-01	0.0667
3636	INPPL1	LZE22D1	Human	Esophagus	HGIN	8.08e-04	1.66e-01	0.0595
3636	INPPL1	LZE22T	Human	Esophagus	ESCC	2.32e-02	3.17e-01	0.068
3636	INPPL1	LZE24T	Human	Esophagus	ESCC	4.45e-08	1.60e-01	0.0596
3636	INPPL1	P1T-E	Human	Esophagus	ESCC	2.02e-04	1.69e-01	0.0875
3636	INPPL1	P2T-E	Human	Esophagus	ESCC	1.74e-17	3.67e-01	0.1177
3636	INPPL1	P4T-E	Human	Esophagus	ESCC	2.06e-05	1.05e-01	0.1323
3636	INPPL1	P5T-E	Human	Esophagus	ESCC	5.82e-03	-2.28e-02	0.1327
3636	INPPL1	P8T-E	Human	Esophagus	ESCC	8.39e-17	2.05e-01	0.0889
3636	INPPL1	P10T-E	Human	Esophagus	ESCC	4.95e-10	1.06e-01	0.116
3636	INPPL1	P12T-E	Human	Esophagus	ESCC	5.97e-21	2.27e-01	0.1122

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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
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:00450175	Esophagus	ESCC	glycerolipid biosynthetic process	154/8552	252/18723	5.20e-07	6.96e-06	154
GO:000150317	Esophagus	ESCC	ossification	232/8552	408/18723	3.00e-06	3.40e-05	232
GO:0043434111	Esophagus	ESCC	response to peptide hormone	234/8552	414/18723	4.93e-06	5.21e-05	234
GO:00066446	Esophagus	ESCC	phospholipid metabolic process	218/8552	383/18723	5.37e-06	5.59e-05	218
GO:003286818	Esophagus	ESCC	response to insulin	156/8552	264/18723	7.21e-06	7.20e-05	156
GO:00097919	Esophagus	ESCC	post-embryonic development	56/8552	80/18723	9.08e-06	8.71e-05	56
GO:00060069	Esophagus	ESCC	glucose metabolic process	119/8552	196/18723	1.51e-05	1.36e-04	119
GO:00066505	Esophagus	ESCC	glycerophospholipid metabolic process	174/8552	306/18723	4.92e-05	3.85e-04	174
GO:00315299	Esophagus	ESCC	ruffle organization	39/8552	56/18723	2.44e-04	1.51e-03	39
GO:00971789	Esophagus	ESCC	ruffle assembly	32/8552	44/18723	2.50e-04	1.54e-03	32
GO:00464864	Esophagus	ESCC	glycerolipid metabolic process	211/8552	392/18723	6.51e-04	3.46e-03	211
GO:00603485	Esophagus	ESCC	bone development	115/8552	205/18723	1.67e-03	7.72e-03	115
GO:00487052	Esophagus	ESCC	skeletal system morphogenesis	120/8552	220/18723	4.90e-03	1.89e-02	120
GO:00302586	Esophagus	ESCC	lipid modification	116/8552	212/18723	4.90e-03	1.89e-02	116
GO:00066611	Esophagus	ESCC	phosphatidylinositol biosynthetic process	73/8552	131/18723	1.31e-02	4.28e-02	73
GO:003286821	Liver	HCC	response to insulin	172/7958	264/18723	7.14e-14	4.23e-12	172
GO:000599621	Liver	HCC	monosaccharide metabolic process	167/7958	257/18723	2.31e-13	1.25e-11	167
GO:001931821	Liver	HCC	hexose metabolic process	155/7958	237/18723	7.63e-13	3.90e-11	155
GO:004343422	Liver	HCC	response to peptide hormone	247/7958	414/18723	9.55e-13	4.77e-11	247
GO:000600621	Liver	HCC	glucose metabolic process	128/7958	196/18723	8.60e-11	3.06e-09	128

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa046662	Colorectum	SER	Fc gamma R-mediated phagocytosis	39/1580	97/8465	5.84e-07	9.70e-06	7.04e-06	39
hsa046663	Colorectum	SER	Fc gamma R-mediated phagocytosis	39/1580	97/8465	5.84e-07	9.70e-06	7.04e-06	39
hsa046664	Colorectum	MSS	Fc gamma R-mediated phagocytosis	45/1875	97/8465	9.30e-08	1.56e-06	9.55e-07	45
hsa04910	Colorectum	MSS	Insulin signaling pathway	43/1875	137/8465	7.37e-03	2.84e-02	1.74e-02	43
hsa046665	Colorectum	MSS	Fc gamma R-mediated phagocytosis	45/1875	97/8465	9.30e-08	1.56e-06	9.55e-07	45
hsa049101	Colorectum	MSS	Insulin signaling pathway	43/1875	137/8465	7.37e-03	2.84e-02	1.74e-02	43
hsa046668	Colorectum	CRC	Fc gamma R-mediated phagocytosis	27/1091	97/8465	6.24e-05	1.12e-03	7.57e-04	27
hsa04070	Colorectum	CRC	Phosphatidylinositol signaling system	25/1091	97/8465	4.27e-04	4.60e-03	3.12e-03	25
hsa049104	Colorectum	CRC	Insulin signaling pathway	31/1091	137/8465	1.07e-03	8.91e-03	6.03e-03	31
hsa00562	Colorectum	CRC	Inositol phosphate metabolism	18/1091	73/8465	4.38e-03	2.52e-02	1.71e-02	18
hsa046669	Colorectum	CRC	Fc gamma R-mediated phagocytosis	27/1091	97/8465	6.24e-05	1.12e-03	7.57e-04	27
hsa040701	Colorectum	CRC	Phosphatidylinositol signaling system	25/1091	97/8465	4.27e-04	4.60e-03	3.12e-03	25
hsa049105	Colorectum	CRC	Insulin signaling pathway	31/1091	137/8465	1.07e-03	8.91e-03	6.03e-03	31
hsa005621	Colorectum	CRC	Inositol phosphate metabolism	18/1091	73/8465	4.38e-03	2.52e-02	1.71e-02	18
hsa049109	Esophagus	ESCC	Insulin signaling pathway	89/4205	137/8465	1.97e-04	7.32e-04	3.75e-04	89
hsa0466620	Esophagus	ESCC	Fc gamma R-mediated phagocytosis	63/4205	97/8465	1.63e-03	4.89e-03	2.50e-03	63
hsa0491014	Esophagus	ESCC	Insulin signaling pathway	89/4205	137/8465	1.97e-04	7.32e-04	3.75e-04	89
hsa04666110	Esophagus	ESCC	Fc gamma R-mediated phagocytosis	63/4205	97/8465	1.63e-03	4.89e-03	2.50e-03	63
hsa0491041	Liver	HCC	Insulin signaling pathway	95/4020	137/8465	1.53e-07	1.97e-06	1.10e-06	95
hsa0466610	Liver	HCC	Fc gamma R-mediated phagocytosis	58/4020	97/8465	9.65e-03	2.52e-02	1.40e-02	58

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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

INPPL1

SNV

Missense_Mutation

c.409N>A

p.Glu137Lys

p.E137K

O15357

protein_coding

tolerated(0.13)

possibly_damaging(0.76)

TCGA-A2-A0EQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

INPPL1

SNV

Missense_Mutation

c.1214N>A

p.Cys405Tyr

p.C405Y

O15357

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

INPPL1

SNV

Missense_Mutation

c.1408N>C

p.Gly470Arg

p.G470R

O15357

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AC-A23C-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

chemo

INPPL1

SNV

Missense_Mutation

c.3556C>A

p.Pro1186Thr

p.P1186T

O15357

protein_coding

tolerated(0.58)

benign(0.018)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

INPPL1

SNV

Missense_Mutation

novel

c.2515N>T

p.Val839Phe

p.V839F

O15357

protein_coding

deleterious(0)

benign(0.386)

TCGA-AN-A0FW-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

INPPL1

SNV

Missense_Mutation

c.2653N>T

p.Leu885Phe

p.L885F

O15357

protein_coding

deleterious(0.02)

possibly_damaging(0.737)

TCGA-D8-A1XQ-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

INPPL1

SNV

Missense_Mutation

rs376117918

c.1636G>A

p.Val546Ile

p.V546I

O15357

protein_coding

tolerated(0.13)

benign(0.179)

TCGA-E2-A1LL-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

docetaxel

INPPL1

SNV

Missense_Mutation

novel

c.629N>A

p.Thr210Asn

p.T210N

O15357

protein_coding

deleterious(0.02)

possibly_damaging(0.806)

TCGA-OL-A5D7-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cytoxan

INPPL1

SNV

Missense_Mutation

novel

c.1681N>T

p.His561Tyr

p.H561Y

O15357

protein_coding

deleterious(0)

probably_damaging(0.99)

TCGA-Z7-A8R6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxol

INPPL1

insertion

Frame_Shift_Ins

novel

c.780_781insGTTTCACCATGTTGGCCAGGGTGGT

p.Leu261ValfsTer51

p.L261Vfs*51

O15357

protein_coding

TCGA-A2-A0CP-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

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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
3636	INPPL1	KINASE, ENZYME, DRUGGABLE GENOME		ANTISENSE OLIGONUCLEOTIDES		10958682
3636	INPPL1	KINASE, ENZYME, DRUGGABLE GENOME	inhibitor	252827535

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