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: PIK3R1

Gene summary for PIK3R1

Gene summary.

Gene information	Species	Human
	Gene symbol	PIK3R1
	Gene ID	5295
	Gene name	phosphoinositide-3-kinase regulatory subunit 1
	Gene Alias	AGM7
	Cytomap	5q13.1
	Gene Type	protein-coding
	GO ID	GO:0000902
	UniProtAcc	P27986

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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
5295	PIK3R1	GSM4909281	Human	Breast	IDC	1.28e-04	-2.60e-01	0.21
5295	PIK3R1	GSM4909285	Human	Breast	IDC	1.43e-02	1.56e-01	0.21
5295	PIK3R1	GSM4909286	Human	Breast	IDC	3.00e-05	-2.63e-01	0.1081
5295	PIK3R1	GSM4909296	Human	Breast	IDC	7.49e-04	-1.36e-01	0.1524
5295	PIK3R1	GSM4909297	Human	Breast	IDC	4.30e-05	-2.58e-01	0.1517
5295	PIK3R1	GSM4909298	Human	Breast	IDC	7.32e-03	-1.92e-01	0.1551
5295	PIK3R1	GSM4909299	Human	Breast	IDC	1.22e-09	5.26e-01	0.035
5295	PIK3R1	GSM4909304	Human	Breast	IDC	3.92e-03	-2.25e-01	0.1636
5295	PIK3R1	GSM4909308	Human	Breast	IDC	2.01e-02	1.25e-01	0.158
5295	PIK3R1	GSM4909311	Human	Breast	IDC	1.37e-15	-2.78e-01	0.1534
5295	PIK3R1	GSM4909312	Human	Breast	IDC	4.51e-15	-3.43e-01	0.1552
5295	PIK3R1	GSM4909316	Human	Breast	IDC	4.59e-02	3.87e-01	0.21
5295	PIK3R1	GSM4909319	Human	Breast	IDC	1.27e-16	-2.64e-01	0.1563
5295	PIK3R1	GSM4909321	Human	Breast	IDC	1.48e-07	-2.46e-01	0.1559
5295	PIK3R1	brca10	Human	Breast	Precancer	1.99e-03	-2.91e-01	-0.0029
5295	PIK3R1	NCCBC3	Human	Breast	DCIS	4.11e-07	4.45e-01	0.1198
5295	PIK3R1	P1	Human	Breast	IDC	4.44e-05	6.22e-02	0.1527
5295	PIK3R1	P2	Human	Breast	IDC	1.46e-05	4.70e-01	0.21
5295	PIK3R1	DCIS2	Human	Breast	DCIS	3.32e-68	6.67e-01	0.0085
5295	PIK3R1	CA_HPV_1	Human	Cervix	CC	1.17e-08	-3.12e-01	0.0264

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
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
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:00971939	Breast	Precancer	intrinsic apoptotic signaling pathway	59/1080	288/18723	8.07e-18	3.60e-15	59
GO:00083809	Breast	Precancer	RNA splicing	65/1080	434/18723	1.27e-12	2.53e-10	65
GO:00434849	Breast	Precancer	regulation of RNA splicing	34/1080	148/18723	2.66e-12	4.75e-10	34
GO:00069869	Breast	Precancer	response to unfolded protein	28/1080	137/18723	3.81e-09	3.00e-07	28
GO:00359669	Breast	Precancer	response to topologically incorrect protein	29/1080	159/18723	3.00e-08	1.89e-06	29
GO:00349769	Breast	Precancer	response to endoplasmic reticulum stress	38/1080	256/18723	7.89e-08	4.60e-06	38
GO:00346209	Breast	Precancer	cellular response to unfolded protein	21/1080	96/18723	9.80e-08	5.46e-06	21
GO:00359679	Breast	Precancer	cellular response to topologically incorrect protein	22/1080	116/18723	6.84e-07	2.80e-05	22
GO:00508219	Breast	Precancer	protein stabilization	29/1080	191/18723	1.67e-06	6.08e-05	29
GO:00316479	Breast	Precancer	regulation of protein stability	38/1080	298/18723	3.73e-06	1.19e-04	38
GO:00300999	Breast	Precancer	myeloid cell differentiation	45/1080	381/18723	4.00e-06	1.25e-04	45
GO:00018196	Breast	Precancer	positive regulation of cytokine production	52/1080	467/18723	4.18e-06	1.29e-04	52
GO:00971919	Breast	Precancer	extrinsic apoptotic signaling pathway	30/1080	219/18723	9.42e-06	2.50e-04	30
GO:19058979	Breast	Precancer	regulation of response to endoplasmic reticulum stress	16/1080	82/18723	1.53e-05	3.75e-04	16
GO:00309687	Breast	Precancer	endoplasmic reticulum unfolded protein response	15/1080	74/18723	1.74e-05	4.17e-04	15
GO:00456379	Breast	Precancer	regulation of myeloid cell differentiation	28/1080	210/18723	3.05e-05	6.72e-04	28
GO:19037069	Breast	Precancer	regulation of hemopoiesis	41/1080	367/18723	3.95e-05	8.52e-04	41
GO:19029039	Breast	Precancer	regulation of supramolecular fiber organization	42/1080	383/18723	4.92e-05	1.04e-03	42
GO:00025737	Breast	Precancer	myeloid leukocyte differentiation	27/1080	208/18723	6.72e-05	1.35e-03	27
GO:00093148	Breast	Precancer	response to radiation	47/1080	456/18723	8.39e-05	1.62e-03	47

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0513118	Breast	Precancer	Shigellosis	44/684	247/8465	3.91e-07	6.86e-06	5.26e-06	44
hsa0513119	Breast	Precancer	Shigellosis	44/684	247/8465	3.91e-07	6.86e-06	5.26e-06	44
hsa0502023	Breast	IDC	Prion disease	102/867	273/8465	3.70e-34	4.01e-32	3.00e-32	102
hsa0517124	Breast	IDC	Coronavirus disease - COVID-19	86/867	232/8465	1.50e-28	9.72e-27	7.27e-27	86
hsa0501023	Breast	IDC	Alzheimer disease	107/867	384/8465	1.70e-23	7.88e-22	5.90e-22	107
hsa0520824	Breast	IDC	Chemical carcinogenesis - reactive oxygen species	71/867	223/8465	2.55e-19	7.53e-18	5.63e-18	71
hsa0541523	Breast	IDC	Diabetic cardiomyopathy	67/867	203/8465	3.17e-19	8.59e-18	6.43e-18	67
hsa0493223	Breast	IDC	Non-alcoholic fatty liver disease	50/867	155/8465	3.48e-14	8.08e-13	6.05e-13	50
hsa0491523	Breast	IDC	Estrogen signaling pathway	35/867	138/8465	2.55e-07	5.18e-06	3.88e-06	35
hsa0516922	Breast	IDC	Epstein-Barr virus infection	45/867	202/8465	3.16e-07	6.05e-06	4.52e-06	45
hsa0541824	Breast	IDC	Fluid shear stress and atherosclerosis	34/867	139/8465	9.41e-07	1.61e-05	1.20e-05	34
hsa0421824	Breast	IDC	Cellular senescence	35/867	156/8465	5.49e-06	7.43e-05	5.56e-05	35
hsa0520523	Breast	IDC	Proteoglycans in cancer	42/867	205/8465	7.69e-06	9.99e-05	7.48e-05	42
hsa0421022	Breast	IDC	Apoptosis	31/867	136/8465	1.34e-05	1.61e-04	1.20e-04	31
hsa0513124	Breast	IDC	Shigellosis	47/867	247/8465	1.78e-05	2.00e-04	1.49e-04	47
hsa0516723	Breast	IDC	Kaposi sarcoma-associated herpesvirus infection	38/867	194/8465	5.87e-05	5.96e-04	4.46e-04	38
hsa0516624	Breast	IDC	Human T-cell leukemia virus 1 infection	40/867	222/8465	2.52e-04	2.21e-03	1.66e-03	40
hsa0516324	Breast	IDC	Human cytomegalovirus infection	39/867	225/8465	6.66e-04	5.41e-03	4.05e-03	39
hsa0406623	Breast	IDC	HIF-1 signaling pathway	22/867	109/8465	1.36e-03	1.00e-02	7.50e-03	22
hsa0510024	Breast	IDC	Bacterial invasion of epithelial cells	17/867	77/8465	1.69e-03	1.19e-02	8.93e-03	17

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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

PIK3R1

SNV

Missense_Mutation

novel

c.1218N>A

p.Asn406Lys

p.N406K

P27986

protein_coding

tolerated(0.08)

benign(0.414)

TCGA-AO-A0JG-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

PIK3R1

SNV

Missense_Mutation

novel

c.166N>G

p.Leu56Val

p.L56V

P27986

protein_coding

deleterious(0.02)

possibly_damaging(0.734)

TCGA-AO-A1KT-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

fluorouracil

PIK3R1

SNV

Missense_Mutation

c.1390N>A

p.Asp464Asn

p.D464N

P27986

protein_coding

deleterious(0)

probably_damaging(0.986)

TCGA-AR-A0TQ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

PIK3R1

SNV

Missense_Mutation

c.1529N>T

p.Glu510Val

p.E510V

P27986

protein_coding

deleterious(0)

possibly_damaging(0.895)

TCGA-AR-A24M-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

tamoxiphen

PIK3R1

SNV

Missense_Mutation

c.1676T>C

p.Ile559Thr

p.I559T

P27986

protein_coding

tolerated(0.19)

possibly_damaging(0.499)

TCGA-BH-A1FD-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PIK3R1

SNV

Missense_Mutation

c.1319N>G

p.Asp440Gly

p.D440G

P27986

protein_coding

deleterious(0.02)

benign(0.108)

TCGA-C8-A135-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

PIK3R1

SNV

Missense_Mutation

novel

c.166T>G

p.Leu56Val

p.L56V

P27986

protein_coding

deleterious(0.02)

possibly_damaging(0.734)

TCGA-D8-A1JK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PIK3R1

SNV

Missense_Mutation

c.1930G>T

p.Gly644Cys

p.G644C

P27986

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-D8-A1XK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine+cyclophosphamide

PIK3R1

SNV

Missense_Mutation

c.2007T>A

p.His669Gln

p.H669Q

P27986

protein_coding

deleterious(0)

probably_damaging(0.992)

TCGA-D8-A1XK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine+cyclophosphamide

PIK3R1

SNV

Missense_Mutation

c.1930N>A

p.Gly644Ser

p.G644S

P27986

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-D8-A1XQ-01

Breast

breast invasive carcinoma

Female

>=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
5295	PIK3R1	CLINICALLY ACTIONABLE, ENZYME, KINASE, DRUGGABLE GENOME, PHOSPHATIDYLINOSITOL 3 KINASE		ZSTK474
5295	PIK3R1	CLINICALLY ACTIONABLE, ENZYME, KINASE, DRUGGABLE GENOME, PHOSPHATIDYLINOSITOL 3 KINASE	inhibitor	CHEMBL3545324	RG-7666
5295	PIK3R1	CLINICALLY ACTIONABLE, ENZYME, KINASE, DRUGGABLE GENOME, PHOSPHATIDYLINOSITOL 3 KINASE	inhibitor	CHEMBL1079593	VS-5584
5295	PIK3R1	CLINICALLY ACTIONABLE, ENZYME, KINASE, DRUGGABLE GENOME, PHOSPHATIDYLINOSITOL 3 KINASE	inhibitor	CHEMBL592445	GEDATOLISIB
5295	PIK3R1	CLINICALLY ACTIONABLE, ENZYME, KINASE, DRUGGABLE GENOME, PHOSPHATIDYLINOSITOL 3 KINASE	inhibitor	CHEMBL2326966	SF-1126
5295	PIK3R1	CLINICALLY ACTIONABLE, ENZYME, KINASE, DRUGGABLE GENOME, PHOSPHATIDYLINOSITOL 3 KINASE	inhibitor	DACTOLISIB	DACTOLISIB
5295	PIK3R1	CLINICALLY ACTIONABLE, ENZYME, KINASE, DRUGGABLE GENOME, PHOSPHATIDYLINOSITOL 3 KINASE	inhibitor	CHEMBL3545088	PUQUITINIB
5295	PIK3R1	CLINICALLY ACTIONABLE, ENZYME, KINASE, DRUGGABLE GENOME, PHOSPHATIDYLINOSITOL 3 KINASE	inhibitor	BUPARLISIB HYDROCHLORIDE
5295	PIK3R1	CLINICALLY ACTIONABLE, ENZYME, KINASE, DRUGGABLE GENOME, PHOSPHATIDYLINOSITOL 3 KINASE	inhibitor	CHEMBL521851	PICTILISIB
5295	PIK3R1	CLINICALLY ACTIONABLE, ENZYME, KINASE, DRUGGABLE GENOME, PHOSPHATIDYLINOSITOL 3 KINASE	inhibitor	PWT33597

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