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: PIK3R2

Gene summary for PIK3R2

Gene summary.

Gene information	Species	Human
	Gene symbol	PIK3R2
	Gene ID	5296
	Gene name	phosphoinositide-3-kinase regulatory subunit 2
	Gene Alias	MPPH
	Cytomap	19p13.11
	Gene Type	protein-coding
	GO ID	GO:0000165
	UniProtAcc	O00459

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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
5296	PIK3R2	HCC1_Meng	Human	Liver	HCC	4.99e-19	6.51e-02	0.0246
5296	PIK3R2	HCC1	Human	Liver	HCC	2.21e-18	3.73e+00	0.5336
5296	PIK3R2	HCC2	Human	Liver	HCC	2.04e-31	3.90e+00	0.5341
5296	PIK3R2	HCC5	Human	Liver	HCC	8.72e-08	6.80e-01	0.4932
5296	PIK3R2	S014	Human	Liver	HCC	6.94e-03	7.10e-02	0.2254
5296	PIK3R2	S015	Human	Liver	HCC	5.89e-08	1.53e-01	0.2375
5296	PIK3R2	S016	Human	Liver	HCC	8.90e-03	8.63e-02	0.2243

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Liver		HCC: Hepatocellular carcinoma
Liver		NAFLD: Non-alcoholic fatty liver disease

∗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:007259422	Liver	HCC	establishment of protein localization to organelle	299/7958	422/18723	1.06e-32	6.10e-30	299
GO:003497612	Liver	HCC	response to endoplasmic reticulum stress	189/7958	256/18723	1.43e-24	4.06e-22	189
GO:190382922	Liver	HCC	positive regulation of cellular protein localization	199/7958	276/18723	1.15e-23	2.62e-21	199
GO:003238621	Liver	HCC	regulation of intracellular transport	231/7958	337/18723	1.99e-22	3.40e-20	231
GO:000691322	Liver	HCC	nucleocytoplasmic transport	208/7958	301/18723	5.51e-21	8.12e-19	208
GO:005116922	Liver	HCC	nuclear transport	208/7958	301/18723	5.51e-21	8.12e-19	208
GO:003315721	Liver	HCC	regulation of intracellular protein transport	165/7958	229/18723	8.37e-20	1.15e-17	165
GO:003238821	Liver	HCC	positive regulation of intracellular transport	148/7958	202/18723	5.15e-19	6.66e-17	148
GO:001050621	Liver	HCC	regulation of autophagy	210/7958	317/18723	7.59e-18	8.45e-16	210
GO:009031621	Liver	HCC	positive regulation of intracellular protein transport	121/7958	160/18723	1.27e-17	1.39e-15	121
GO:003450421	Liver	HCC	protein localization to nucleus	194/7958	290/18723	2.84e-17	2.85e-15	194
GO:190495122	Liver	HCC	positive regulation of establishment of protein localization	207/7958	319/18723	3.95e-16	3.29e-14	207
GO:005122222	Liver	HCC	positive regulation of protein transport	194/7958	303/18723	2.41e-14	1.56e-12	194
GO:003286821	Liver	HCC	response to insulin	172/7958	264/18723	7.14e-14	4.23e-12	172
GO:001703811	Liver	HCC	protein import	140/7958	206/18723	1.12e-13	6.46e-12	140
GO:003286921	Liver	HCC	cellular response to insulin stimulus	137/7958	203/18723	4.69e-13	2.44e-11	137
GO:004343422	Liver	HCC	response to peptide hormone	247/7958	414/18723	9.55e-13	4.77e-11	247
GO:004682221	Liver	HCC	regulation of nucleocytoplasmic transport	81/7958	106/18723	1.11e-12	5.52e-11	81
GO:007137521	Liver	HCC	cellular response to peptide hormone stimulus	179/7958	290/18723	2.54e-11	9.88e-10	179
GO:190018212	Liver	HCC	positive regulation of protein localization to nucleus	67/7958	87/18723	5.43e-11	2.00e-09	67

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0516421	Liver	HCC	Influenza A	101/4020	171/8465	1.41e-03	5.07e-03	2.82e-03	101
hsa040128	Liver	HCC	ErbB signaling pathway	54/4020	85/8465	2.02e-03	7.07e-03	3.93e-03	54
hsa042138	Liver	HCC	Longevity regulating pathway - multiple species	41/4020	62/8465	2.30e-03	7.86e-03	4.37e-03	41
hsa049334	Liver	HCC	AGE-RAGE signaling pathway in diabetic complications	62/4020	100/8465	2.35e-03	7.95e-03	4.42e-03	62
hsa052032	Liver	HCC	Viral carcinogenesis	117/4020	204/8465	2.68e-03	8.98e-03	5.00e-03	117
hsa052224	Liver	HCC	Small cell lung cancer	57/4020	92/8465	3.54e-03	1.12e-02	6.22e-03	57
hsa052232	Liver	HCC	Non-small cell lung cancer	46/4020	72/8465	3.61e-03	1.12e-02	6.22e-03	46
hsa0516721	Liver	HCC	Kaposi sarcoma-associated herpesvirus infection	111/4020	194/8465	3.78e-03	1.16e-02	6.45e-03	111
hsa040718	Liver	HCC	Sphingolipid signaling pathway	72/4020	121/8465	5.01e-03	1.47e-02	8.18e-03	72
hsa052142	Liver	HCC	Glioma	47/4020	75/8465	5.67e-03	1.62e-02	9.02e-03	47
hsa0467042	Liver	HCC	Leukocyte transendothelial migration	68/4020	114/8465	5.79e-03	1.64e-02	9.15e-03	68
hsa05142	Liver	HCC	Chagas disease	61/4020	102/8465	8.04e-03	2.17e-02	1.21e-02	61
hsa049262	Liver	HCC	Relaxin signaling pathway	75/4020	129/8465	9.33e-03	2.46e-02	1.37e-02	75
hsa0466610	Liver	HCC	Fc gamma R-mediated phagocytosis	58/4020	97/8465	9.65e-03	2.52e-02	1.40e-02	58
hsa0152121	Liver	HCC	EGFR tyrosine kinase inhibitor resistance	48/4020	79/8465	1.19e-02	2.99e-02	1.66e-02	48
hsa01522	Liver	HCC	Endocrine resistance	58/4020	98/8465	1.28e-02	3.19e-02	1.78e-02	58
hsa04917	Liver	HCC	Prolactin signaling pathway	43/4020	70/8465	1.30e-02	3.19e-02	1.78e-02	43
hsa0523021	Liver	HCC	Central carbon metabolism in cancer	43/4020	70/8465	1.30e-02	3.19e-02	1.78e-02	43
hsa051612	Liver	HCC	Hepatitis B	91/4020	162/8465	1.56e-02	3.76e-02	2.09e-02	91
hsa05221	Liver	HCC	Acute myeloid leukemia	41/4020	67/8465	1.64e-02	3.90e-02	2.17e-02	41

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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

PIK3R2

SNV

Missense_Mutation

novel

c.930G>T

p.Lys310Asn

p.K310N

O00459

protein_coding

tolerated(0.11)

probably_damaging(0.991)

TCGA-A2-A25C-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

PIK3R2

SNV

Missense_Mutation

c.1528N>T

p.Arg510Trp

p.R510W

O00459

protein_coding

deleterious(0)

probably_damaging(0.965)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PIK3R2

SNV

Missense_Mutation

c.1211N>G

p.His404Arg

p.H404R

O00459

protein_coding

deleterious(0)

possibly_damaging(0.556)

TCGA-D8-A1XQ-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PIK3R2

SNV

Missense_Mutation

rs779519249

c.55C>T

p.Arg19Trp

p.R19W

O00459

protein_coding

deleterious(0.02)

probably_damaging(0.925)

TCGA-LL-A9Q3-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Immunotherapy

herceptin

PIK3R2

insertion

Nonsense_Mutation

novel

c.1765_1766insTGGTCCTTTTCAAGCCCTTTGTAAAGTTTGCCCTTT

p.Lys589delinsMetValLeuPheLysProPheValLysPheAlaLeuTer

p.K589delinsMVLFKPFVKFAL*

O00459

protein_coding

TCGA-AN-A0FV-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PIK3R2

insertion

Frame_Shift_Ins

novel

c.1234_1235insCCCCCCTAAGG

p.Gln412ProfsTer69

p.Q412Pfs*69

O00459

protein_coding

TCGA-B6-A0I9-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

PIK3R2

insertion

In_Frame_Ins

novel

c.1270_1271insAGGTGGAGGTTG

p.Pro424delinsGlnValGluValAla

p.P424delinsQVEVA

O00459

protein_coding

TCGA-BH-A0B8-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

PIK3R2

SNV

Missense_Mutation

novel

c.377C>T

p.Pro126Leu

p.P126L

O00459

protein_coding

tolerated(0.1)

benign(0.007)

TCGA-5M-AAT6-01

Colorectum

colon adenocarcinoma

Female

<65

III/IV

Unknown

PIK3R2

SNV

Missense_Mutation

c.400N>A

p.Ala134Thr

p.A134T

O00459

protein_coding

deleterious(0.03)

benign(0.136)

TCGA-A6-2682-01

Colorectum

colon adenocarcinoma

Male

>=65

III/IV

Chemotherapy

PIK3R2

SNV

Missense_Mutation

c.1592N>A

p.Arg531His

p.R531H

O00459

protein_coding

deleterious(0)

probably_damaging(0.985)

TCGA-AD-6901-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Chemotherapy

xeloda

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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
5296	PIK3R2	CLINICALLY ACTIONABLE, KINASE, PHOSPHATIDYLINOSITOL 3 KINASE, ENZYME, DRUG RESISTANCE	inhibitor	PF-4691502	PF-04691502
5296	PIK3R2	CLINICALLY ACTIONABLE, KINASE, PHOSPHATIDYLINOSITOL 3 KINASE, ENZYME, DRUG RESISTANCE	inhibitor	CHEMBL1236962	OMIPALISIB
5296	PIK3R2	CLINICALLY ACTIONABLE, KINASE, PHOSPHATIDYLINOSITOL 3 KINASE, ENZYME, DRUG RESISTANCE		cyclophosphamide	CYCLOPHOSPHAMIDE
5296	PIK3R2	CLINICALLY ACTIONABLE, KINASE, PHOSPHATIDYLINOSITOL 3 KINASE, ENZYME, DRUG RESISTANCE	inhibitor	PKI-587	GEDATOLISIB
5296	PIK3R2	CLINICALLY ACTIONABLE, KINASE, PHOSPHATIDYLINOSITOL 3 KINASE, ENZYME, DRUG RESISTANCE	inhibitor	CHEMBL3545096	BGT-226
5296	PIK3R2	CLINICALLY ACTIONABLE, KINASE, PHOSPHATIDYLINOSITOL 3 KINASE, ENZYME, DRUG RESISTANCE	inhibitor	BKM120	BUPARLISIB
5296	PIK3R2	CLINICALLY ACTIONABLE, KINASE, PHOSPHATIDYLINOSITOL 3 KINASE, ENZYME, DRUG RESISTANCE	inhibitor	CHEMBL3544999	SAMOTOLISIB
5296	PIK3R2	CLINICALLY ACTIONABLE, KINASE, PHOSPHATIDYLINOSITOL 3 KINASE, ENZYME, DRUG RESISTANCE	inhibitor	CHEMBL586701	ZSTK-474
5296	PIK3R2	CLINICALLY ACTIONABLE, KINASE, PHOSPHATIDYLINOSITOL 3 KINASE, ENZYME, DRUG RESISTANCE	inhibitor	SF1126
5296	PIK3R2	CLINICALLY ACTIONABLE, KINASE, PHOSPHATIDYLINOSITOL 3 KINASE, ENZYME, DRUG RESISTANCE	inhibitor	GSK2126458	OMIPALISIB

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