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: RMND1

Gene summary for RMND1

Gene summary.

Gene information	Species	Human
	Gene symbol	RMND1
	Gene ID	55005
	Gene name	required for meiotic nuclear division 1 homolog
	Gene Alias	C6orf96
	Cytomap	6q25.1
	Gene Type	protein-coding
	GO ID	GO:0006412
	UniProtAcc	A0A087WXU0

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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
55005	RMND1	PTC01	Human	Thyroid	PTC	8.46e-12	1.94e-01	0.1899
55005	RMND1	PTC04	Human	Thyroid	PTC	2.48e-20	2.12e-01	0.1927
55005	RMND1	PTC05	Human	Thyroid	PTC	2.38e-23	6.92e-01	0.2065
55005	RMND1	PTC06	Human	Thyroid	PTC	5.69e-29	5.46e-01	0.2057
55005	RMND1	PTC07	Human	Thyroid	PTC	9.99e-34	5.08e-01	0.2044
55005	RMND1	ATC11	Human	Thyroid	ATC	2.92e-02	2.57e-01	0.3386
55005	RMND1	ATC12	Human	Thyroid	ATC	9.04e-10	1.04e-01	0.34
55005	RMND1	ATC13	Human	Thyroid	ATC	3.09e-16	1.81e-01	0.34
55005	RMND1	ATC2	Human	Thyroid	ATC	4.49e-08	6.16e-01	0.34
55005	RMND1	ATC3	Human	Thyroid	ATC	5.67e-05	3.00e-01	0.338
55005	RMND1	ATC4	Human	Thyroid	ATC	1.37e-09	1.29e-01	0.34
55005	RMND1	ATC5	Human	Thyroid	ATC	1.33e-15	2.12e-01	0.34

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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
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:000641714	Breast	IDC	regulation of translation	74/1434	468/18723	1.67e-09	1.53e-07	74
GO:004572714	Breast	IDC	positive regulation of translation	33/1434	136/18723	1.92e-09	1.73e-07	33
GO:003425014	Breast	IDC	positive regulation of cellular amide metabolic process	35/1434	162/18723	1.63e-08	1.16e-06	35
GO:00325432	Breast	IDC	mitochondrial translation	13/1434	76/18723	4.81e-03	3.67e-02	13
GO:000641724	Breast	DCIS	regulation of translation	72/1390	468/18723	2.46e-09	2.17e-07	72
GO:004572724	Breast	DCIS	positive regulation of translation	32/1390	136/18723	3.56e-09	3.10e-07	32
GO:003425023	Breast	DCIS	positive regulation of cellular amide metabolic process	34/1390	162/18723	2.60e-08	1.73e-06	34
GO:003254311	Breast	DCIS	mitochondrial translation	13/1390	76/18723	3.70e-03	2.99e-02	13
GO:014005313	Esophagus	ESCC	mitochondrial gene expression	93/8552	108/18723	1.96e-18	2.03e-16	93
GO:0006417111	Esophagus	ESCC	regulation of translation	304/8552	468/18723	1.53e-17	1.33e-15	304
GO:003254314	Esophagus	ESCC	mitochondrial translation	68/8552	76/18723	1.02e-15	6.86e-14	68
GO:0045727111	Esophagus	ESCC	positive regulation of translation	107/8552	136/18723	2.79e-15	1.68e-13	107
GO:0034250111	Esophagus	ESCC	positive regulation of cellular amide metabolic process	123/8552	162/18723	3.32e-15	1.93e-13	123
GO:00701292	Esophagus	ESCC	regulation of mitochondrial translation	22/8552	24/18723	2.82e-06	3.21e-05	22
GO:00621252	Esophagus	ESCC	regulation of mitochondrial gene expression	24/8552	28/18723	1.37e-05	1.25e-04	24
GO:00701312	Esophagus	ESCC	positive regulation of mitochondrial translation	14/8552	15/18723	1.47e-04	9.85e-04	14
GO:000641722	Liver	HCC	regulation of translation	287/7958	468/18723	8.79e-17	8.08e-15	287
GO:01400531	Liver	HCC	mitochondrial gene expression	82/7958	108/18723	1.49e-12	7.20e-11	82
GO:00325431	Liver	HCC	mitochondrial translation	62/7958	76/18723	2.95e-12	1.34e-10	62
GO:004572712	Liver	HCC	positive regulation of translation	97/7958	136/18723	8.51e-12	3.55e-10	97

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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

RMND1

SNV

Missense_Mutation

c.20G>A

p.Arg7Lys

p.R7K

Q9NWS8

protein_coding

tolerated_low_confidence(0.21)

benign(0.027)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

RMND1

SNV

Missense_Mutation

c.103G>A

p.Glu35Lys

p.E35K

Q9NWS8

protein_coding

tolerated_low_confidence(0.26)

benign(0)

TCGA-BH-A0DZ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

docetaxel

RMND1

SNV

Missense_Mutation

c.163N>G

p.Pro55Ala

p.P55A

Q9NWS8

protein_coding

tolerated_low_confidence(0.22)

benign(0.211)

TCGA-D8-A13Z-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine

RMND1

SNV

Missense_Mutation

c.275N>G

p.Lys92Arg

p.K92R

Q9NWS8

protein_coding

tolerated(0.29)

benign(0)

TCGA-E2-A15D-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

RMND1

SNV

Missense_Mutation

rs138900217

c.329N>C

p.Lys110Thr

p.K110T

Q9NWS8

protein_coding

tolerated(0.09)

benign(0.003)

TCGA-EW-A1IZ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

taxotere

RMND1

SNV

Missense_Mutation

novel

c.565N>G

p.Gln189Glu

p.Q189E

Q9NWS8

protein_coding

tolerated(0.33)

benign(0.013)

TCGA-GM-A3NW-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

fluorouracil

RMND1

insertion

Frame_Shift_Ins

novel

c.881_882insAGAGAATATACAATTTCTACCTAATAAAATTATGAAATTTC

p.Asp294GlufsTer16

p.D294Efs*16

Q9NWS8

protein_coding

TCGA-A2-A0EV-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

RMND1

insertion

Nonsense_Mutation

novel

c.320_321insCTTTGAAGCCTAATAAATATCCAAAG

p.Thr108PhefsTer4

p.T108Ffs*4

Q9NWS8

protein_coding

TCGA-AQ-A04J-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

RMND1

SNV

Missense_Mutation

c.49N>C

p.Ser17Pro

p.S17P

Q9NWS8

protein_coding

tolerated_low_confidence(0.06)

benign(0)

TCGA-FU-A23L-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

RMND1

SNV

Missense_Mutation

novel

c.242C>A

p.Ser81Tyr

p.S81Y

Q9NWS8

protein_coding

tolerated_low_confidence(0.18)

benign(0)

TCGA-IR-A3LK-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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