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: NTRK1

Gene summary for NTRK1

Gene summary.

Gene information	Species	Human
	Gene symbol	NTRK1
	Gene ID	4914
	Gene name	neurotrophic receptor tyrosine kinase 1
	Gene Alias	MTC
	Cytomap	1q23.1
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	P04629

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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
4914	NTRK1	HTA11_3410_2000001011	Human	Colorectum	AD	5.41e-44	7.41e-01	0.0155
4914	NTRK1	HTA11_2487_2000001011	Human	Colorectum	SER	2.77e-16	4.96e-01	-0.1808
4914	NTRK1	HTA11_2951_2000001011	Human	Colorectum	AD	9.44e-15	7.95e-01	0.0216
4914	NTRK1	HTA11_1938_2000001011	Human	Colorectum	AD	1.82e-26	8.66e-01	-0.0811
4914	NTRK1	HTA11_78_2000001011	Human	Colorectum	AD	4.49e-03	1.73e-01	-0.1088
4914	NTRK1	HTA11_347_2000001011	Human	Colorectum	AD	8.68e-40	7.00e-01	-0.1954
4914	NTRK1	HTA11_411_2000001011	Human	Colorectum	SER	1.80e-15	1.13e+00	-0.2602
4914	NTRK1	HTA11_2112_2000001011	Human	Colorectum	SER	1.27e-03	6.07e-01	-0.2196
4914	NTRK1	HTA11_3361_2000001011	Human	Colorectum	AD	1.79e-23	8.57e-01	-0.1207
4914	NTRK1	HTA11_83_2000001011	Human	Colorectum	SER	3.15e-17	6.54e-01	-0.1526
4914	NTRK1	HTA11_696_2000001011	Human	Colorectum	AD	4.78e-48	1.19e+00	-0.1464
4914	NTRK1	HTA11_866_2000001011	Human	Colorectum	AD	3.31e-19	3.71e-01	-0.1001
4914	NTRK1	HTA11_1391_2000001011	Human	Colorectum	AD	1.60e-19	5.51e-01	-0.059
4914	NTRK1	HTA11_2992_2000001011	Human	Colorectum	SER	8.52e-33	1.44e+00	-0.1706
4914	NTRK1	HTA11_5212_2000001011	Human	Colorectum	AD	5.75e-30	1.25e+00	-0.2061
4914	NTRK1	HTA11_5216_2000001011	Human	Colorectum	SER	5.84e-22	1.37e+00	-0.1462
4914	NTRK1	HTA11_546_2000001011	Human	Colorectum	AD	9.18e-34	1.17e+00	-0.0842
4914	NTRK1	HTA11_6818_2000001011	Human	Colorectum	AD	1.81e-04	2.53e-01	0.0112
4914	NTRK1	HTA11_99999965104_69814	Human	Colorectum	MSS	7.64e-19	5.35e-01	0.281

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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

∗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:0009410	Colorectum	AD	response to xenobiotic stimulus	128/3918	462/18723	2.69e-04	3.31e-03	128
GO:0007568	Colorectum	AD	aging	98/3918	339/18723	2.77e-04	3.39e-03	98
GO:0043547	Colorectum	AD	positive regulation of GTPase activity	75/3918	255/18723	7.95e-04	7.91e-03	75
GO:0043523	Colorectum	AD	regulation of neuron apoptotic process	64/3918	212/18723	8.95e-04	8.63e-03	64
GO:0061458	Colorectum	AD	reproductive system development	116/3918	427/18723	1.11e-03	1.01e-02	116
GO:1901888	Colorectum	AD	regulation of cell junction assembly	61/3918	204/18723	1.50e-03	1.27e-02	61
GO:0048608	Colorectum	AD	reproductive structure development	114/3918	424/18723	1.78e-03	1.47e-02	114
GO:0046578	Colorectum	AD	regulation of Ras protein signal transduction	56/3918	189/18723	2.85e-03	2.14e-02	56
GO:0042490	Colorectum	AD	mechanoreceptor differentiation	24/3918	67/18723	3.48e-03	2.52e-02	24
GO:0051091	Colorectum	AD	positive regulation of DNA-binding transcription factor activity	73/3918	260/18723	3.52e-03	2.54e-02	73
GO:0050808	Colorectum	AD	synapse organization	112/3918	426/18723	4.25e-03	2.92e-02	112
GO:0060009	Colorectum	AD	Sertoli cell development	7/3918	12/18723	5.09e-03	3.38e-02	7
GO:0048017	Colorectum	AD	inositol lipid-mediated signaling	53/3918	182/18723	5.35e-03	3.52e-02	53
GO:0048015	Colorectum	AD	phosphatidylinositol-mediated signaling	52/3918	178/18723	5.37e-03	3.54e-02	52
GO:0007411	Colorectum	AD	axon guidance	64/3918	227/18723	5.41e-03	3.55e-02	64
GO:0050807	Colorectum	AD	regulation of synapse organization	60/3918	211/18723	5.67e-03	3.64e-02	60
GO:0038083	Colorectum	AD	peptidyl-tyrosine autophosphorylation	10/3918	21/18723	5.71e-03	3.64e-02	10
GO:0097485	Colorectum	AD	neuron projection guidance	64/3918	228/18723	6.02e-03	3.78e-02	64
GO:0043524	Colorectum	AD	negative regulation of neuron apoptotic process	43/3918	145/18723	8.04e-03	4.73e-02	43
GO:00020641	Colorectum	SER	epithelial cell development	64/2897	220/18723	1.96e-07	1.10e-05	64

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa04722	Colorectum	AD	Neurotrophin signaling pathway	50/2092	119/8465	2.28e-05	2.24e-04	1.43e-04	50
hsa05216	Colorectum	AD	Thyroid cancer	21/2092	37/8465	3.05e-05	2.76e-04	1.76e-04	21
hsa05230	Colorectum	AD	Central carbon metabolism in cancer	33/2092	70/8465	3.61e-05	3.19e-04	2.03e-04	33
hsa047221	Colorectum	AD	Neurotrophin signaling pathway	50/2092	119/8465	2.28e-05	2.24e-04	1.43e-04	50
hsa052161	Colorectum	AD	Thyroid cancer	21/2092	37/8465	3.05e-05	2.76e-04	1.76e-04	21
hsa052301	Colorectum	AD	Central carbon metabolism in cancer	33/2092	70/8465	3.61e-05	3.19e-04	2.03e-04	33
hsa052302	Colorectum	SER	Central carbon metabolism in cancer	25/1580	70/8465	5.43e-04	4.51e-03	3.27e-03	25
hsa047222	Colorectum	SER	Neurotrophin signaling pathway	35/1580	119/8465	2.80e-03	2.02e-02	1.47e-02	35
hsa052303	Colorectum	SER	Central carbon metabolism in cancer	25/1580	70/8465	5.43e-04	4.51e-03	3.27e-03	25
hsa047223	Colorectum	SER	Neurotrophin signaling pathway	35/1580	119/8465	2.80e-03	2.02e-02	1.47e-02	35
hsa052162	Colorectum	MSS	Thyroid cancer	21/1875	37/8465	4.98e-06	6.00e-05	3.68e-05	21
hsa047224	Colorectum	MSS	Neurotrophin signaling pathway	45/1875	119/8465	7.04e-05	6.55e-04	4.02e-04	45
hsa04210	Colorectum	MSS	Apoptosis	44/1875	136/8465	3.66e-03	1.66e-02	1.01e-02	44
hsa052304	Colorectum	MSS	Central carbon metabolism in cancer	25/1875	70/8465	6.50e-03	2.64e-02	1.62e-02	25
hsa052163	Colorectum	MSS	Thyroid cancer	21/1875	37/8465	4.98e-06	6.00e-05	3.68e-05	21
hsa047225	Colorectum	MSS	Neurotrophin signaling pathway	45/1875	119/8465	7.04e-05	6.55e-04	4.02e-04	45
hsa042101	Colorectum	MSS	Apoptosis	44/1875	136/8465	3.66e-03	1.66e-02	1.01e-02	44
hsa052305	Colorectum	MSS	Central carbon metabolism in cancer	25/1875	70/8465	6.50e-03	2.64e-02	1.62e-02	25

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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
NGF	NTRK1	NGF_NTRK1	NT	Endometrium	AEH
NTF3	NTRK1	NTF3_NTRK1	NT	Endometrium	AEH

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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

NTRK1

SNV

Missense_Mutation

novel

c.586N>A

p.Leu196Met

p.L196M

P04629

protein_coding

deleterious(0.01)

possibly_damaging(0.652)

TCGA-A1-A0SO-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

NTRK1

SNV

Missense_Mutation

c.956N>A

p.Gly319Asp

p.G319D

P04629

protein_coding

tolerated(0.09)

benign(0.236)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NTRK1

SNV

Missense_Mutation

c.1112C>T

p.Ser371Phe

p.S371F

P04629

protein_coding

deleterious(0.02)

benign(0.163)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NTRK1

SNV

Missense_Mutation

c.1876N>A

p.Gln626Lys

p.Q626K

P04629

protein_coding

deleterious(0.01)

benign(0.038)

TCGA-B6-A0I8-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

NTRK1

SNV

Missense_Mutation

rs770090356

c.1025N>A

p.Arg342Gln

p.R342Q

P04629

protein_coding

tolerated(0.6)

benign(0.001)

TCGA-BH-A0EB-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

NTRK1

SNV

Missense_Mutation

c.1748G>A

p.Arg583His

p.R583H

P04629

protein_coding

deleterious(0.01)

possibly_damaging(0.685)

TCGA-D8-A1J8-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

nolvadex

NTRK1

SNV

Missense_Mutation

c.286N>G

p.Leu96Val

p.L96V

P04629

protein_coding

deleterious(0)

probably_damaging(0.944)

TCGA-EW-A1P7-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

NTRK1

SNV

Missense_Mutation

novel

c.625N>C

p.Asp209His

p.D209H

P04629

protein_coding

deleterious(0.01)

possibly_damaging(0.802)

TCGA-OL-A66J-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NTRK1

insertion

Nonsense_Mutation

novel

c.1089_1090insGGTTGAG

p.Ala364GlyfsTer2

p.A364Gfs*2

P04629

protein_coding

TCGA-A8-A07R-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Ancillary

zoledronic

NTRK1

insertion

Frame_Shift_Ins

novel

c.1091_1092insGCAGA

p.Asn365GlnfsTer107

p.N365Qfs*107

P04629

protein_coding

TCGA-A8-A07R-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Ancillary

zoledronic

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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
4914	NTRK1	KINASE, TYROSINE KINASE, DRUGGABLE GENOME, CLINICALLY ACTIONABLE, CELL SURFACE, DRUG RESISTANCE		Pyrazolo[1,5-a]pyrimidine derivative 17
4914	NTRK1	KINASE, TYROSINE KINASE, DRUGGABLE GENOME, CLINICALLY ACTIONABLE, CELL SURFACE, DRUG RESISTANCE		GAMMA-INTERFERON		8144393
4914	NTRK1	KINASE, TYROSINE KINASE, DRUGGABLE GENOME, CLINICALLY ACTIONABLE, CELL SURFACE, DRUG RESISTANCE		Pyrrolo[2,3-b]pyridine derivative 3
4914	NTRK1	KINASE, TYROSINE KINASE, DRUGGABLE GENOME, CLINICALLY ACTIONABLE, CELL SURFACE, DRUG RESISTANCE		Pyrazolo[1,5-a]pyrimidine derivative 18
4914	NTRK1	KINASE, TYROSINE KINASE, DRUGGABLE GENOME, CLINICALLY ACTIONABLE, CELL SURFACE, DRUG RESISTANCE	inhibitor	381744939
4914	NTRK1	KINASE, TYROSINE KINASE, DRUGGABLE GENOME, CLINICALLY ACTIONABLE, CELL SURFACE, DRUG RESISTANCE		N-acylpiperidine ether derivative 6
4914	NTRK1	KINASE, TYROSINE KINASE, DRUGGABLE GENOME, CLINICALLY ACTIONABLE, CELL SURFACE, DRUG RESISTANCE		N-acylpiperidine ether derivative 3
4914	NTRK1	KINASE, TYROSINE KINASE, DRUGGABLE GENOME, CLINICALLY ACTIONABLE, CELL SURFACE, DRUG RESISTANCE	inhibitor	252827366	GILTERITINIB
4914	NTRK1	KINASE, TYROSINE KINASE, DRUGGABLE GENOME, CLINICALLY ACTIONABLE, CELL SURFACE, DRUG RESISTANCE		LESTAURTINIB	LESTAURTINIB
4914	NTRK1	KINASE, TYROSINE KINASE, DRUGGABLE GENOME, CLINICALLY ACTIONABLE, CELL SURFACE, DRUG RESISTANCE		PMID28270021-Compound-WO2016054807Example71

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