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: HAL

Gene summary for HAL

Gene summary.

Gene information	Species	Human
	Gene symbol	HAL
	Gene ID	3034
	Gene name	histidine ammonia-lyase
	Gene Alias	HIS
	Cytomap	12q23.1
	Gene Type	protein-coding
	GO ID	GO:0006082
	UniProtAcc	P42357

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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
3034	HAL	NAFLD1	Human	Liver	NAFLD	6.35e-14	1.15e+00	-0.04
3034	HAL	S41	Human	Liver	Cirrhotic	7.93e-06	7.92e-01	-0.0343
3034	HAL	S43	Human	Liver	Cirrhotic	8.29e-03	-1.98e-01	-0.0187
3034	HAL	HCC1_Meng	Human	Liver	HCC	2.10e-74	9.44e-02	0.0246
3034	HAL	HCC2_Meng	Human	Liver	HCC	7.91e-05	-2.35e-01	0.0107
3034	HAL	cirrhotic1	Human	Liver	Cirrhotic	1.04e-02	-2.34e-01	0.0202
3034	HAL	cirrhotic2	Human	Liver	Cirrhotic	5.21e-03	-2.29e-01	0.0201

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Liver		HCC: Hepatocellular carcinoma
Liver		NAFLD: Non-alcoholic fatty liver disease

∗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:00463953	Liver	NAFLD	carboxylic acid catabolic process	73/1882	236/18723	4.16e-19	1.22e-15	73
GO:00160544	Liver	NAFLD	organic acid catabolic process	73/1882	240/18723	1.20e-18	2.34e-15	73
GO:00442825	Liver	NAFLD	small molecule catabolic process	91/1882	376/18723	8.96e-16	1.31e-12	91
GO:0009063	Liver	NAFLD	cellular amino acid catabolic process	36/1882	110/18723	6.56e-11	1.99e-08	36
GO:00065203	Liver	NAFLD	cellular amino acid metabolic process	63/1882	284/18723	1.14e-09	2.17e-07	63
GO:19016053	Liver	NAFLD	alpha-amino acid metabolic process	46/1882	195/18723	2.74e-08	2.86e-06	46
GO:00436483	Liver	NAFLD	dicarboxylic acid metabolic process	22/1882	96/18723	1.73e-04	3.08e-03	22
GO:004428211	Liver	Cirrhotic	small molecule catabolic process	151/4634	376/18723	2.20e-11	1.34e-09	151
GO:001605411	Liver	Cirrhotic	organic acid catabolic process	104/4634	240/18723	1.91e-10	9.53e-09	104
GO:004639511	Liver	Cirrhotic	carboxylic acid catabolic process	102/4634	236/18723	3.41e-10	1.63e-08	102
GO:19016051	Liver	Cirrhotic	alpha-amino acid metabolic process	82/4634	195/18723	7.72e-08	2.30e-06	82
GO:00090631	Liver	Cirrhotic	cellular amino acid catabolic process	49/4634	110/18723	4.47e-06	7.42e-05	49
GO:000652011	Liver	Cirrhotic	cellular amino acid metabolic process	103/4634	284/18723	8.88e-06	1.30e-04	103
GO:004364811	Liver	Cirrhotic	dicarboxylic acid metabolic process	43/4634	96/18723	1.42e-05	1.97e-04	43
GO:004428221	Liver	HCC	small molecule catabolic process	225/7958	376/18723	6.50e-12	2.80e-10	225
GO:001605421	Liver	HCC	organic acid catabolic process	152/7958	240/18723	5.11e-11	1.92e-09	152
GO:00463952	Liver	HCC	carboxylic acid catabolic process	149/7958	236/18723	1.11e-10	3.87e-09	149
GO:19016052	Liver	HCC	alpha-amino acid metabolic process	124/7958	195/18723	2.07e-09	5.79e-08	124
GO:00436482	Liver	HCC	dicarboxylic acid metabolic process	68/7958	96/18723	1.73e-08	4.14e-07	68
GO:00065202	Liver	HCC	cellular amino acid metabolic process	167/7958	284/18723	1.91e-08	4.56e-07	167

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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

HAL

SNV

Missense_Mutation

novel

c.17N>C

p.Val6Ala

p.V6A

P42357

protein_coding

tolerated_low_confidence(0.07)

benign(0.017)

TCGA-A2-A3Y0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

HAL

SNV

Missense_Mutation

c.1770N>C

p.Trp590Cys

p.W590C

P42357

protein_coding

deleterious(0.01)

probably_damaging(0.932)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

HAL

SNV

Missense_Mutation

c.844N>A

p.Asp282Asn

p.D282N

P42357

protein_coding

tolerated(0.19)

benign(0.031)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

HAL

SNV

Missense_Mutation

c.971N>C

p.Ser324Thr

p.S324T

P42357

protein_coding

tolerated(0.61)

benign(0.015)

TCGA-AO-A0JF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

doxorubicin

HAL

SNV

Missense_Mutation

c.259N>A

p.Asp87Asn

p.D87N

P42357

protein_coding

tolerated_low_confidence(0.16)

benign(0.003)

TCGA-C8-A12L-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

HAL

insertion

Frame_Shift_Ins

novel

c.251_252insTCACATTTGCCCCAATTTACAGATC

p.Glu85HisfsTer11

p.E85Hfs*11

P42357

protein_coding

TCGA-A8-A09E-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

anastrozole

HAL

SNV

Missense_Mutation

c.1505N>T

p.Thr502Met

p.T502M

P42357

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-LP-A4AV-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

HAL

SNV

Missense_Mutation

rs758667702

c.85N>T

p.Arg29Trp

p.R29W

P42357

protein_coding

deleterious_low_confidence(0.03)

benign(0.221)

TCGA-AA-3950-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

HAL

SNV

Missense_Mutation

c.1688N>A

p.Gly563Asp

p.G563D

P42357

protein_coding

deleterious(0)

probably_damaging(0.974)

TCGA-AA-A010-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Chemotherapy

folinic

HAL

SNV

Missense_Mutation

novel

c.1447C>G

p.Pro483Ala

p.P483A

P42357

protein_coding

deleterious(0)

probably_damaging(0.951)

TCGA-AA-A01D-01

Colorectum

colon adenocarcinoma

Female

<65

III/IV

Chemotherapy

capecitabine

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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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