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: ALAS1

Gene summary for ALAS1

Gene summary.

Gene information	Species	Human
	Gene symbol	ALAS1
	Gene ID	211
	Gene name	5'-aminolevulinate synthase 1
	Gene Alias	ALAS
	Cytomap	3p21.2
	Gene Type	protein-coding
	GO ID	GO:0002262
	UniProtAcc	P13196

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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
211	ALAS1	LZE4T	Human	Esophagus	ESCC	1.39e-03	2.76e-01	0.0811
211	ALAS1	LZE5T	Human	Esophagus	ESCC	4.84e-02	2.20e-01	0.0514
211	ALAS1	LZE7T	Human	Esophagus	ESCC	9.11e-05	2.91e-01	0.0667
211	ALAS1	LZE24T	Human	Esophagus	ESCC	2.09e-13	5.38e-01	0.0596
211	ALAS1	LZE6T	Human	Esophagus	ESCC	3.77e-05	2.21e-01	0.0845
211	ALAS1	P1T-E	Human	Esophagus	ESCC	8.98e-06	3.05e-01	0.0875
211	ALAS1	P2T-E	Human	Esophagus	ESCC	2.83e-18	3.36e-01	0.1177
211	ALAS1	P4T-E	Human	Esophagus	ESCC	3.17e-21	5.74e-01	0.1323
211	ALAS1	P5T-E	Human	Esophagus	ESCC	5.15e-06	1.43e-01	0.1327
211	ALAS1	P8T-E	Human	Esophagus	ESCC	1.24e-07	1.93e-01	0.0889
211	ALAS1	P9T-E	Human	Esophagus	ESCC	1.56e-07	2.60e-01	0.1131
211	ALAS1	P10T-E	Human	Esophagus	ESCC	3.02e-03	1.64e-01	0.116
211	ALAS1	P11T-E	Human	Esophagus	ESCC	5.83e-09	4.67e-01	0.1426
211	ALAS1	P12T-E	Human	Esophagus	ESCC	3.20e-20	4.94e-01	0.1122
211	ALAS1	P15T-E	Human	Esophagus	ESCC	1.06e-15	2.24e-01	0.1149
211	ALAS1	P16T-E	Human	Esophagus	ESCC	8.47e-12	2.97e-01	0.1153
211	ALAS1	P17T-E	Human	Esophagus	ESCC	5.65e-03	1.94e-01	0.1278
211	ALAS1	P19T-E	Human	Esophagus	ESCC	1.39e-03	4.58e-01	0.1662
211	ALAS1	P20T-E	Human	Esophagus	ESCC	1.18e-11	4.08e-01	0.1124
211	ALAS1	P21T-E	Human	Esophagus	ESCC	1.12e-15	3.88e-01	0.1617

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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

∗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:0030099111	Esophagus	ESCC	myeloid cell differentiation	232/8552	381/18723	1.22e-09	2.90e-08	232
GO:0002262111	Esophagus	ESCC	myeloid cell homeostasis	104/8552	157/18723	1.49e-07	2.36e-06	104
GO:0034101111	Esophagus	ESCC	erythrocyte homeostasis	88/8552	129/18723	1.81e-07	2.84e-06	88
GO:0048872111	Esophagus	ESCC	homeostasis of number of cells	163/8552	272/18723	1.40e-06	1.69e-05	163
GO:0030218111	Esophagus	ESCC	erythrocyte differentiation	80/8552	120/18723	2.69e-06	3.08e-05	80
GO:00067791	Esophagus	ESCC	porphyrin-containing compound biosynthetic process	23/8552	31/18723	1.20e-03	5.88e-03	23
GO:00330141	Esophagus	ESCC	tetrapyrrole biosynthetic process	23/8552	31/18723	1.20e-03	5.88e-03	23
GO:00461482	Esophagus	ESCC	pigment biosynthetic process	40/8552	62/18723	2.14e-03	9.54e-03	40
GO:00067832	Esophagus	ESCC	heme biosynthetic process	20/8552	27/18723	2.61e-03	1.11e-02	20
GO:00330132	Esophagus	ESCC	tetrapyrrole metabolic process	37/8552	59/18723	6.23e-03	2.29e-02	37
GO:00424401	Esophagus	ESCC	pigment metabolic process	50/8552	84/18723	7.34e-03	2.64e-02	50
GO:00421681	Esophagus	ESCC	heme metabolic process	27/8552	42/18723	1.16e-02	3.90e-02	27
GO:00488727	Liver	NAFLD	homeostasis of number of cells	43/1882	272/18723	1.86e-03	1.91e-02	43
GO:00341017	Liver	NAFLD	erythrocyte homeostasis	24/1882	129/18723	2.18e-03	2.12e-02	24
GO:00022627	Liver	NAFLD	myeloid cell homeostasis	27/1882	157/18723	3.85e-03	3.28e-02	27
GO:00300997	Liver	NAFLD	myeloid cell differentiation	55/1882	381/18723	3.86e-03	3.28e-02	55
GO:0061515	Liver	NAFLD	myeloid cell development	15/1882	71/18723	4.12e-03	3.44e-02	15
GO:003009912	Liver	Cirrhotic	myeloid cell differentiation	135/4634	381/18723	1.69e-06	3.22e-05	135
GO:003410112	Liver	Cirrhotic	erythrocyte homeostasis	54/4634	129/18723	1.41e-05	1.97e-04	54
GO:00302187	Liver	Cirrhotic	erythrocyte differentiation	50/4634	120/18723	3.35e-05	4.13e-04	50

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa012405	Esophagus	ESCC	Biosynthesis of cofactors	97/4205	153/8465	3.88e-04	1.35e-03	6.94e-04	97
hsa0124012	Esophagus	ESCC	Biosynthesis of cofactors	97/4205	153/8465	3.88e-04	1.35e-03	6.94e-04	97
hsa01240	Liver	Cirrhotic	Biosynthesis of cofactors	66/2530	153/8465	3.11e-04	1.99e-03	1.23e-03	66
hsa00260	Liver	Cirrhotic	Glycine, serine and threonine metabolism	22/2530	40/8465	7.85e-04	4.51e-03	2.78e-03	22
hsa012401	Liver	Cirrhotic	Biosynthesis of cofactors	66/2530	153/8465	3.11e-04	1.99e-03	1.23e-03	66
hsa002601	Liver	Cirrhotic	Glycine, serine and threonine metabolism	22/2530	40/8465	7.85e-04	4.51e-03	2.78e-03	22
hsa012402	Liver	HCC	Biosynthesis of cofactors	103/4020	153/8465	4.67e-07	5.05e-06	2.81e-06	103
hsa002602	Liver	HCC	Glycine, serine and threonine metabolism	28/4020	40/8465	3.28e-03	1.07e-02	5.93e-03	28
hsa012403	Liver	HCC	Biosynthesis of cofactors	103/4020	153/8465	4.67e-07	5.05e-06	2.81e-06	103
hsa002603	Liver	HCC	Glycine, serine and threonine metabolism	28/4020	40/8465	3.28e-03	1.07e-02	5.93e-03	28
hsa012404	Oral cavity	OSCC	Biosynthesis of cofactors	88/3704	153/8465	3.84e-04	1.20e-03	6.12e-04	88
hsa0124011	Oral cavity	OSCC	Biosynthesis of cofactors	88/3704	153/8465	3.84e-04	1.20e-03	6.12e-04	88
hsa0124021	Oral cavity	LP	Biosynthesis of cofactors	57/2418	153/8465	1.17e-02	3.91e-02	2.52e-02	57
hsa0124031	Oral cavity	LP	Biosynthesis of cofactors	57/2418	153/8465	1.17e-02	3.91e-02	2.52e-02	57

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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

ALAS1

SNV

Missense_Mutation

c.238N>A

p.Asp80Asn

p.D80N

P13196

protein_coding

tolerated_low_confidence(0.62)

benign(0)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ALAS1

SNV

Missense_Mutation

c.673N>G

p.Arg225Gly

p.R225G

P13196

protein_coding

tolerated(0.33)

benign(0.079)

TCGA-D8-A1XQ-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ALAS1

SNV

Missense_Mutation

novel

c.487N>G

p.Pro163Ala

p.P163A

P13196

protein_coding

tolerated(0.86)

benign(0)

TCGA-LL-A8F5-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

ALAS1

insertion

Nonsense_Mutation

novel

c.1449_1450insCTACACAAAATAAAAATTTAAAAAATCAGCCA

p.Gly484LeufsTer7

p.G484Lfs*7

P13196

protein_coding

TCGA-AO-A0J2-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

ALAS1

SNV

Missense_Mutation

novel

c.701A>G

p.Asp234Gly

p.D234G

P13196

protein_coding

deleterious(0.01)

benign(0.434)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

ALAS1

SNV

Missense_Mutation

novel

c.1787A>G

p.Gln596Arg

p.Q596R

P13196

protein_coding

tolerated(0.26)

benign(0)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

ALAS1

SNV

Missense_Mutation

novel

c.953N>T

p.Ser318Leu

p.S318L

P13196

protein_coding

deleterious(0)

possibly_damaging(0.904)

TCGA-C5-A3HE-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

ALAS1

SNV

Missense_Mutation

rs140582251

c.916N>A

p.Ala306Thr

p.A306T

P13196

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-EA-A410-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

ALAS1

SNV

Missense_Mutation

novel

c.1241N>T

p.His414Leu

p.H414L

P13196

protein_coding

deleterious(0)

probably_damaging(0.988)

TCGA-MA-AA42-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

ALAS1

SNV

Missense_Mutation

rs769075509

c.20G>A

p.Arg7His

p.R7H

P13196

protein_coding

tolerated(0.26)

benign(0.125)

TCGA-VS-A9UY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

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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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