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: SPIDR

Gene summary for SPIDR

Gene summary.

Gene information	Species	Human
	Gene symbol	SPIDR
	Gene ID	23514
	Gene name	scaffold protein involved in DNA repair
	Gene Alias	KIAA0146
	Cytomap	8q11.21
	Gene Type	protein-coding
	GO ID	GO:0000018
	UniProtAcc	Q14159

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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
23514	SPIDR	CCI_1	Human	Cervix	CC	5.35e-21	1.85e+00	0.528
23514	SPIDR	CCI_2	Human	Cervix	CC	3.41e-11	1.49e+00	0.5249
23514	SPIDR	CCI_3	Human	Cervix	CC	3.75e-20	1.48e+00	0.516
23514	SPIDR	CCII_1	Human	Cervix	CC	1.28e-12	6.32e-01	0.3249
23514	SPIDR	HTA11_3410_2000001011	Human	Colorectum	AD	1.66e-26	-6.41e-01	0.0155
23514	SPIDR	HTA11_2487_2000001011	Human	Colorectum	SER	1.12e-06	-4.49e-01	-0.1808
23514	SPIDR	HTA11_3361_2000001011	Human	Colorectum	AD	1.59e-02	-4.47e-01	-0.1207
23514	SPIDR	HTA11_5216_2000001011	Human	Colorectum	SER	1.84e-04	-7.56e-01	-0.1462
23514	SPIDR	HTA11_9341_2000001011	Human	Colorectum	SER	2.70e-02	-5.55e-01	-0.00410000000000005
23514	SPIDR	HTA11_7862_2000001011	Human	Colorectum	AD	2.45e-03	-3.45e-01	-0.0179
23514	SPIDR	HTA11_866_3004761011	Human	Colorectum	AD	2.12e-03	-3.98e-01	0.096
23514	SPIDR	HTA11_8622_2000001021	Human	Colorectum	SER	7.56e-08	-7.21e-01	0.0528
23514	SPIDR	HTA11_7469_2000001011	Human	Colorectum	AD	7.57e-04	-7.03e-01	-0.0124
23514	SPIDR	HTA11_99999970781_79442	Human	Colorectum	MSS	6.12e-06	-4.58e-01	0.294
23514	SPIDR	HTA11_99999965062_69753	Human	Colorectum	MSI-H	3.86e-02	3.79e-01	0.3487
23514	SPIDR	HTA11_99999965104_69814	Human	Colorectum	MSS	1.06e-03	4.83e-01	0.281
23514	SPIDR	F007	Human	Colorectum	FAP	6.43e-04	-7.30e-02	0.1176
23514	SPIDR	A015-C-203	Human	Colorectum	FAP	1.21e-28	-3.51e-01	-0.1294
23514	SPIDR	A015-C-204	Human	Colorectum	FAP	1.61e-09	-3.44e-01	-0.0228
23514	SPIDR	A014-C-040	Human	Colorectum	FAP	6.30e-07	-3.42e-01	-0.1184

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
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
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ

∗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:00725949	Cervix	CC	establishment of protein localization to organelle	99/2311	422/18723	1.23e-10	2.11e-08	99
GO:004325410	Cervix	CC	regulation of protein-containing complex assembly	96/2311	428/18723	2.91e-09	3.05e-07	96
GO:003133410	Cervix	CC	positive regulation of protein-containing complex assembly	55/2311	237/18723	2.25e-06	6.73e-05	55
GO:00712148	Cervix	CC	cellular response to abiotic stimulus	69/2311	331/18723	7.36e-06	1.73e-04	69
GO:01040048	Cervix	CC	cellular response to environmental stimulus	69/2311	331/18723	7.36e-06	1.73e-04	69
GO:00714798	Cervix	CC	cellular response to ionizing radiation	22/2311	72/18723	3.47e-05	5.60e-04	22
GO:00093149	Cervix	CC	response to radiation	86/2311	456/18723	3.50e-05	5.63e-04	86
GO:00714786	Cervix	CC	cellular response to radiation	41/2311	186/18723	1.41e-04	1.71e-03	41
GO:20010209	Cervix	CC	regulation of response to DNA damage stimulus	46/2311	219/18723	1.92e-04	2.23e-03	46
GO:00102126	Cervix	CC	response to ionizing radiation	34/2311	148/18723	2.23e-04	2.53e-03	34
GO:00510528	Cervix	CC	regulation of DNA metabolic process	65/2311	359/18723	9.25e-04	7.84e-03	65
GO:00973059	Cervix	CC	response to alcohol	46/2311	253/18723	4.40e-03	2.69e-02	46
GO:0072594	Colorectum	AD	establishment of protein localization to organelle	148/3918	422/18723	7.95e-12	1.04e-09	148
GO:0043254	Colorectum	AD	regulation of protein-containing complex assembly	148/3918	428/18723	2.64e-11	3.18e-09	148
GO:0031334	Colorectum	AD	positive regulation of protein-containing complex assembly	91/3918	237/18723	4.78e-10	3.99e-08	91
GO:0051052	Colorectum	AD	regulation of DNA metabolic process	116/3918	359/18723	2.47e-07	1.00e-05	116
GO:0051054	Colorectum	AD	positive regulation of DNA metabolic process	73/3918	201/18723	3.27e-07	1.29e-05	73
GO:2001020	Colorectum	AD	regulation of response to DNA damage stimulus	71/3918	219/18723	4.38e-05	7.65e-04	71
GO:0071241	Colorectum	AD	cellular response to inorganic substance	68/3918	226/18723	6.98e-04	7.10e-03	68
GO:2001022	Colorectum	AD	positive regulation of response to DNA damage stimulus	36/3918	105/18723	1.02e-03	9.47e-03	36

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Enriched KEGG pathways.

Pathway ID

Tissue

Disease Stage

Description

Gene Ratio

Bg Ratio

pvalue

p.adjust

qvalue

Count

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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

SPIDR

SNV

Missense_Mutation

c.715N>G

p.Gln239Glu

p.Q239E

Q14159

protein_coding

tolerated(0.14)

benign(0.199)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

SPIDR

SNV

Missense_Mutation

novel

c.278N>T

p.Thr93Ile

p.T93I

Q14159

protein_coding

tolerated(0.09)

benign(0.089)

TCGA-A8-A06T-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

anastrozole

SPIDR

SNV

Missense_Mutation

novel

c.1010N>A

p.Gly337Glu

p.G337E

Q14159

protein_coding

tolerated(0.46)

benign(0.332)

TCGA-AC-A3W7-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

femara

SPIDR

SNV

Missense_Mutation

novel

c.319G>A

p.Asp107Asn

p.D107N

Q14159

protein_coding

tolerated(0.11)

probably_damaging(0.996)

TCGA-AN-A0AS-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

SPIDR

SNV

Missense_Mutation

c.1955N>G

p.Thr652Arg

p.T652R

Q14159

protein_coding

tolerated(1)

benign(0)

TCGA-B6-A0RE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SPIDR

SNV

Missense_Mutation

rs777561291

c.2068N>T

p.Leu690Phe

p.L690F

Q14159

protein_coding

tolerated(0.06)

probably_damaging(0.967)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

SPIDR

SNV

Missense_Mutation

rs782141616

c.1045G>A

p.Ala349Thr

p.A349T

Q14159

protein_coding

deleterious(0)

probably_damaging(0.989)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SPIDR

SNV

Missense_Mutation

c.1127N>A

p.Cys376Tyr

p.C376Y

Q14159

protein_coding

tolerated(0.18)

benign(0.003)

TCGA-C8-A12Y-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SPIDR

SNV

Missense_Mutation

rs375968682

c.2654N>C

p.Cys885Ser

p.C885S

Q14159

protein_coding

deleterious(0.01)

probably_damaging(0.998)

TCGA-E9-A1R5-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

SPIDR

insertion

Frame_Shift_Ins

novel

c.2740_2741insTT

p.Glu914ValfsTer61

p.E914Vfs*61

Q14159

protein_coding

TCGA-AO-A0J9-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

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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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