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: NUMA1

Gene summary for NUMA1

Gene summary.

Gene information	Species	Human
	Gene symbol	NUMA1
	Gene ID	4926
	Gene name	nuclear mitotic apparatus protein 1
	Gene Alias	NMP-22
	Cytomap	11q13.4
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	A0A024R5M9

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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
4926	NUMA1	GSM4909291	Human	Breast	IDC	1.09e-03	3.98e-01	0.1753
4926	NUMA1	GSM4909296	Human	Breast	IDC	2.17e-03	2.94e-02	0.1524
4926	NUMA1	GSM4909297	Human	Breast	IDC	2.40e-07	-1.25e-01	0.1517
4926	NUMA1	GSM4909311	Human	Breast	IDC	8.26e-12	-3.16e-02	0.1534
4926	NUMA1	GSM4909312	Human	Breast	IDC	3.12e-02	3.94e-02	0.1552
4926	NUMA1	GSM4909319	Human	Breast	IDC	7.92e-15	-1.28e-01	0.1563
4926	NUMA1	GSM4909321	Human	Breast	IDC	5.08e-07	-1.01e-01	0.1559
4926	NUMA1	brca1	Human	Breast	Precancer	1.63e-05	-1.35e-01	-0.0338
4926	NUMA1	M1	Human	Breast	IDC	3.80e-14	5.86e-01	0.1577
4926	NUMA1	M5	Human	Breast	IDC	6.85e-08	8.05e-01	0.1598
4926	NUMA1	P1	Human	Breast	IDC	3.51e-03	1.19e-01	0.1527
4926	NUMA1	DCIS2	Human	Breast	DCIS	1.09e-56	3.51e-01	0.0085
4926	NUMA1	LZE2T	Human	Esophagus	ESCC	3.68e-05	4.70e-01	0.082
4926	NUMA1	LZE4T	Human	Esophagus	ESCC	5.62e-12	4.56e-01	0.0811
4926	NUMA1	LZE5T	Human	Esophagus	ESCC	3.47e-02	1.07e-01	0.0514
4926	NUMA1	LZE7T	Human	Esophagus	ESCC	1.75e-08	2.70e-01	0.0667
4926	NUMA1	LZE8T	Human	Esophagus	ESCC	3.91e-14	1.81e-01	0.067
4926	NUMA1	LZE20T	Human	Esophagus	ESCC	1.88e-07	1.83e-01	0.0662
4926	NUMA1	LZE22D1	Human	Esophagus	HGIN	4.14e-03	5.57e-01	0.0595
4926	NUMA1	LZE22T	Human	Esophagus	ESCC	8.29e-07	1.05e+00	0.068

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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
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
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:00432549	Breast	Precancer	regulation of protein-containing complex assembly	50/1080	428/18723	1.63e-06	5.97e-05	50
GO:00313349	Breast	Precancer	positive regulation of protein-containing complex assembly	33/1080	237/18723	2.39e-06	8.21e-05	33
GO:19029059	Breast	Precancer	positive regulation of supramolecular fiber organization	28/1080	209/18723	2.79e-05	6.28e-04	28
GO:19029039	Breast	Precancer	regulation of supramolecular fiber organization	42/1080	383/18723	4.92e-05	1.04e-03	42
GO:00514959	Breast	Precancer	positive regulation of cytoskeleton organization	28/1080	226/18723	1.13e-04	2.04e-03	28
GO:00085445	Breast	Precancer	epidermis development	35/1080	324/18723	2.71e-04	3.96e-03	35
GO:19038299	Breast	Precancer	positive regulation of cellular protein localization	30/1080	276/18723	6.48e-04	7.99e-03	30
GO:00322739	Breast	Precancer	positive regulation of protein polymerization	18/1080	138/18723	9.85e-04	1.11e-02	18
GO:00099136	Breast	Precancer	epidermal cell differentiation	23/1080	202/18723	1.43e-03	1.50e-02	23
GO:20012529	Breast	Precancer	positive regulation of chromosome organization	12/1080	82/18723	2.51e-03	2.29e-02	12
GO:00302163	Breast	Precancer	keratinocyte differentiation	17/1080	139/18723	2.71e-03	2.39e-02	17
GO:00071638	Breast	Precancer	establishment or maintenance of cell polarity	23/1080	218/18723	3.82e-03	3.06e-02	23
GO:19043757	Breast	Precancer	regulation of protein localization to cell periphery	15/1080	125/18723	5.58e-03	4.07e-02	15
GO:19043778	Breast	Precancer	positive regulation of protein localization to cell periphery	10/1080	69/18723	5.98e-03	4.22e-02	10
GO:190290514	Breast	IDC	positive regulation of supramolecular fiber organization	37/1434	209/18723	1.33e-06	5.75e-05	37
GO:004325414	Breast	IDC	regulation of protein-containing complex assembly	61/1434	428/18723	1.77e-06	7.31e-05	61
GO:003133414	Breast	IDC	positive regulation of protein-containing complex assembly	40/1434	237/18723	1.77e-06	7.31e-05	40
GO:190290314	Breast	IDC	regulation of supramolecular fiber organization	54/1434	383/18723	9.40e-06	2.66e-04	54
GO:003227314	Breast	IDC	positive regulation of protein polymerization	25/1434	138/18723	4.46e-05	1.01e-03	25
GO:005149513	Breast	IDC	positive regulation of cytoskeleton organization	35/1434	226/18723	5.04e-05	1.09e-03	35

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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

NUMA1

SNV

Missense_Mutation

novel

c.3952C>G

p.Gln1318Glu

p.Q1318E

Q14980

protein_coding

tolerated(0.21)

possibly_damaging(0.875)

TCGA-A2-A0D2-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

NUMA1

SNV

Missense_Mutation

novel

c.3160N>T

p.His1054Tyr

p.H1054Y

Q14980

protein_coding

deleterious(0.01)

benign(0.244)

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NUMA1

SNV

Missense_Mutation

rs371974605

c.1784C>T

p.Ser595Phe

p.S595F

Q14980

protein_coding

tolerated(0.09)

benign(0.003)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NUMA1

SNV

Missense_Mutation

c.1474C>T

p.His492Tyr

p.H492Y

Q14980

protein_coding

deleterious(0)

benign(0.058)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NUMA1

SNV

Missense_Mutation

rs768661581

c.1832N>G

p.Lys611Arg

p.K611R

Q14980

protein_coding

tolerated(0.34)

benign(0.254)

TCGA-AC-A2BK-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

cytoxan

NUMA1

SNV

Missense_Mutation

rs780069834

c.5996G>A

p.Gly1999Glu

p.G1999E

Q14980

protein_coding

tolerated(0.21)

benign(0.328)

TCGA-AC-A3W6-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

NUMA1

SNV

Missense_Mutation

novel

c.5995G>A

p.Gly1999Arg

p.G1999R

Q14980

protein_coding

deleterious(0.02)

possibly_damaging(0.701)

TCGA-AC-A3W6-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

NUMA1

SNV

Missense_Mutation

rs1053601

c.2617N>A

p.Glu873Lys

p.E873K

Q14980

protein_coding

tolerated(0.49)

benign(0.019)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NUMA1

SNV

Missense_Mutation

c.1665G>C

p.Gln555His

p.Q555H

Q14980

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-AN-A0AT-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

NUMA1

SNV

Missense_Mutation

rs141331520

c.5501N>T

p.Ser1834Leu

p.S1834L

Q14980

protein_coding

deleterious(0)

possibly_damaging(0.9)

TCGA-AO-A0JA-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

leuprolide

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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
4926	NUMA1	CLINICALLY ACTIONABLE		calcium channel blockers		24192120

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