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: LIMA1

Gene summary for LIMA1

Gene summary.

Gene information	Species	Human
	Gene symbol	LIMA1
	Gene ID	51474
	Gene name	LIM domain and actin binding 1
	Gene Alias	EPLIN
	Cytomap	12q13.12
	Gene Type	protein-coding
	GO ID	GO:0003008
	UniProtAcc	Q9UHB6

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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
51474	LIMA1	HTA11_3410_2000001011	Human	Colorectum	AD	4.64e-07	-4.28e-01	0.0155
51474	LIMA1	HTA11_2487_2000001011	Human	Colorectum	SER	5.42e-03	4.86e-01	-0.1808
51474	LIMA1	HTA11_1938_2000001011	Human	Colorectum	AD	1.02e-14	9.08e-01	-0.0811
51474	LIMA1	HTA11_78_2000001011	Human	Colorectum	AD	4.36e-10	8.84e-01	-0.1088
51474	LIMA1	HTA11_347_2000001011	Human	Colorectum	AD	4.31e-47	1.47e+00	-0.1954
51474	LIMA1	HTA11_411_2000001011	Human	Colorectum	SER	9.42e-23	1.43e+00	-0.2602
51474	LIMA1	HTA11_83_2000001011	Human	Colorectum	SER	3.29e-17	1.11e+00	-0.1526
51474	LIMA1	HTA11_696_2000001011	Human	Colorectum	AD	1.04e-09	7.41e-01	-0.1464
51474	LIMA1	HTA11_866_2000001011	Human	Colorectum	AD	4.67e-10	7.02e-01	-0.1001
51474	LIMA1	HTA11_1391_2000001011	Human	Colorectum	AD	7.08e-11	1.17e+00	-0.059
51474	LIMA1	HTA11_2992_2000001011	Human	Colorectum	SER	6.10e-03	5.73e-01	-0.1706
51474	LIMA1	HTA11_5212_2000001011	Human	Colorectum	AD	5.54e-03	5.95e-01	-0.2061
51474	LIMA1	HTA11_546_2000001011	Human	Colorectum	AD	2.13e-02	5.40e-01	-0.0842
51474	LIMA1	HTA11_866_3004761011	Human	Colorectum	AD	2.86e-04	-5.25e-01	0.096
51474	LIMA1	HTA11_6818_2000001021	Human	Colorectum	AD	9.71e-07	-6.40e-01	0.0588
51474	LIMA1	HTA11_99999970781_79442	Human	Colorectum	MSS	4.31e-16	-5.79e-01	0.294
51474	LIMA1	HTA11_99999971662_82457	Human	Colorectum	MSS	2.57e-21	-6.03e-01	0.3859
51474	LIMA1	HTA11_99999973899_84307	Human	Colorectum	MSS	1.93e-11	-8.36e-01	0.2585
51474	LIMA1	HTA11_99999974143_84620	Human	Colorectum	MSS	4.57e-38	-8.52e-01	0.3005
51474	LIMA1	F007	Human	Colorectum	FAP	4.81e-06	-5.95e-01	0.1176

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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
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
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:00308353	Colorectum	FAP	negative regulation of actin filament depolymerization	14/2622	45/18723	2.53e-03	1.99e-02	14
GO:00432442	Colorectum	FAP	regulation of protein-containing complex disassembly	28/2622	121/18723	4.50e-03	3.06e-02	28
GO:00512612	Colorectum	FAP	protein depolymerization	26/2622	114/18723	7.36e-03	4.40e-02	26
GO:00432421	Colorectum	FAP	negative regulation of protein-containing complex disassembly	20/2622	82/18723	8.23e-03	4.82e-02	20
GO:00226002	Colorectum	FAP	digestive system process	24/2622	104/18723	8.41e-03	4.89e-02	24
GO:00508922	Colorectum	FAP	intestinal absorption	12/2622	41/18723	8.57e-03	4.96e-02	12
GO:00070155	Colorectum	CRC	actin filament organization	104/2078	442/18723	4.75e-14	7.12e-11	104
GO:00329705	Colorectum	CRC	regulation of actin filament-based process	89/2078	397/18723	5.25e-11	3.14e-08	89
GO:19029035	Colorectum	CRC	regulation of supramolecular fiber organization	80/2078	383/18723	1.52e-08	2.75e-06	80
GO:00329565	Colorectum	CRC	regulation of actin cytoskeleton organization	76/2078	358/18723	1.68e-08	2.79e-06	76
GO:01100535	Colorectum	CRC	regulation of actin filament organization	63/2078	278/18723	2.21e-08	3.23e-06	63
GO:00325354	Colorectum	CRC	regulation of cellular component size	79/2078	383/18723	3.30e-08	4.60e-06	79
GO:00081545	Colorectum	CRC	actin polymerization or depolymerization	51/2078	218/18723	1.65e-07	1.72e-05	51
GO:00615724	Colorectum	CRC	actin filament bundle organization	40/2078	161/18723	6.72e-07	4.52e-05	40
GO:00510174	Colorectum	CRC	actin filament bundle assembly	39/2078	157/18723	9.26e-07	5.83e-05	39
GO:00080645	Colorectum	CRC	regulation of actin polymerization or depolymerization	44/2078	188/18723	1.12e-06	6.69e-05	44
GO:00308325	Colorectum	CRC	regulation of actin filament length	44/2078	189/18723	1.31e-06	7.25e-05	44
GO:00329845	Colorectum	CRC	protein-containing complex disassembly	46/2078	224/18723	2.61e-05	7.18e-04	46
GO:00106394	Colorectum	CRC	negative regulation of organelle organization	63/2078	348/18723	6.09e-05	1.35e-03	63
GO:00224115	Colorectum	CRC	cellular component disassembly	75/2078	443/18723	1.26e-04	2.42e-03	75

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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

LIMA1

SNV

Missense_Mutation

c.578C>A

p.Pro193Gln

p.P193Q

Q9UHB6

protein_coding

deleterious(0)

probably_damaging(0.988)

TCGA-A2-A25A-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Cytoxan

LIMA1

SNV

Missense_Mutation

c.772N>C

p.Glu258Gln

p.E258Q

Q9UHB6

protein_coding

deleterious(0.01)

possibly_damaging(0.71)

TCGA-A8-A095-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

LIMA1

SNV

Missense_Mutation

c.2275N>A

p.Glu759Lys

p.E759K

Q9UHB6

protein_coding

deleterious(0.02)

possibly_damaging(0.476)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

LIMA1

SNV

Missense_Mutation

rs763276725

c.889N>A

p.Glu297Lys

p.E297K

Q9UHB6

protein_coding

deleterious(0.04)

probably_damaging(0.996)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

LIMA1

SNV

Missense_Mutation

c.1943A>G

p.Asn648Ser

p.N648S

Q9UHB6

protein_coding

tolerated(1)

benign(0)

TCGA-AO-A128-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

LIMA1

SNV

Missense_Mutation

c.178N>G

p.Leu60Val

p.L60V

Q9UHB6

protein_coding

tolerated(0.09)

benign(0.156)

TCGA-BH-A0HP-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

doxorubicin

LIMA1

SNV

Missense_Mutation

novel

c.823N>A

p.Gln275Lys

p.Q275K

Q9UHB6

protein_coding

deleterious(0)

probably_damaging(0.99)

TCGA-S3-AA11-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

letrozole

LIMA1

SNV

Missense_Mutation

novel

c.1066N>T

p.Pro356Ser

p.P356S

Q9UHB6

protein_coding

tolerated(0.3)

benign(0.01)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

LIMA1

SNV

Missense_Mutation

c.150G>A

p.Met50Ile

p.M50I

Q9UHB6

protein_coding

tolerated(0.49)

benign(0.023)

TCGA-C5-A1BL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

LIMA1

SNV

Missense_Mutation

rs781115938

c.1717N>A

p.Asp573Asn

p.D573N

Q9UHB6

protein_coding

deleterious(0.03)

probably_damaging(0.985)

TCGA-EK-A2RO-01

Cervix

cervical & endocervical cancer

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

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