LncExpDB

Introduction

1 What is LncExpDB?

LncExpDB 2.0 features enriched biological contexts, expanded expression data, scenario-specific functional analyses, and new analytical tools.

LncExpDB is a comprehensive expression database that systematically profiles human long non-coding RNAs (lncRNAs) across multiple biological contexts. In the current version, six new biological contexts—immunotherapy, aging, metabolic disease, neurodegenerative disease, reproduction, and wound healing—have been incorporated, expanding the total to 15 contexts. These contexts collectively cover diverse physiological and pathological processes and are derived from extensive high-quality datasets encompassing 29 datasets and 2,662 samples.
Based on these 15 contexts, LncExpDB provides a global landscape of lncRNA expression, including overall expression profiles, highly expressed lncRNAs, featured lncRNAs with function-linked patterns, and extensive lncRNA–mRNA interaction pairs. To enhance analytical capacity and user experience, two new analytical tools have been integrated, together with an automated pipeline module that supports reproducible data processing and expression analysis. The usage and implementation details of these new tools are documented in the Help section for easy reference.
Collectively, LncExpDB serves as a versatile and user-friendly platform for exploring lncRNA expression, regulation, and functional associations across diverse biological scenarios.

Moreover, LncExpDB is equipped with user-friendly web interfaces, providing functionalities for data query, browsing, visualization as well as easy access.

Data and Methods

2.1 Data collection

LncExpDB collects a total of 29 RNA-seq datasets comprising 2,662 samples were collected from public databases such as GEO, SRA and ArrayExpress, covering 374 biological conditions across 15 biological contexts. These contexts include normal tissues and cell lines, organ development, preimplantation embryos, cell differentiation, subcellular localization, exosomes, cancer cell lines, virus infection, circadian rhythm, and newly added contexts such as tumor immune microenvironment, aging, and other biological processes. In addition, version 2.0 provides enriched expression features, including 44,752 highly expressed genes, 39,253 featured genes, and 35,188,816 lncRNA–mRNA co-expression pairs. To further facilitate biological interpretation, new analytical modules such as LncNet and LncImm have been integrated, supporting context-specific characterization such as tumor immune microenvironment signatures and age-related expression trends. Moreover, the pipeline code has been made publicly available to ensure reproducibility and extensibility.

Biological Context	Project ID	Dataset	Source	Sample Number	PMID
Normal Tissue/Cell	E-MTAB-2836	The Human Protein Atlas	EBI ArrayExpress	121	28940711
	SRP013565	ENCODE Primary Cell Lines	NCBI SRA	111	29126249
Organ Development	E-MTAB-6814	Development of Brain	EBI ArrayExpress	55	31243368
	E-MTAB-6814	Development of Cerebellum	EBI ArrayExpress	59	31243368
	E-MTAB-6814	Development of Heart	EBI ArrayExpress	50	31243368
	E-MTAB-6814	Development of Kidney	EBI ArrayExpress	40	31243368
	E-MTAB-6814	Development of Liver	EBI ArrayExpress	50	31243368
	E-MTAB-6814	Development of Ovary	EBI ArrayExpress	18	31243368
	E-MTAB-6814	Development of Testis	EBI ArrayExpress	41	31243368
Preimplantation Embryo	PRJNA291062	Oocyte to Lateblastocyst (7 Stages)	NCBI SRA	35	27315811
	PRJNA153427	Oocyte to Lateblastocyst (9 Stages)	NCBI SRA	90	23934149
Cell Differentiation	PRJNA504841	Cell Differentiation	NCBI SRA	297	31249060
Subcellular Localization	PRJNA476786	Subcellular Localization	NCBI SRA	36	31230715
Exosome	PRJNA414172	Blood Exosomes from Early-Stage Esophageal Squamous Cell Carcinoma Patients vs. Normal Control	NCBI SRA	12	32043367
	PRJNA390615, PRJNA390988	Blood Exosomes from Colorectal Cancer Patients vs. Normal Control	NCBI SRA	44	30053265
	PRJNA390615, PRJNA390988	Blood Exosomes from Coronary Heart Disease vs. Normal Control	NCBI SRA	38	30053265
	PRJNA390615, PRJNA390988	Blood Exosomes from Hepatocellular Carcinoma vs. Normal Control	NCBI SRA	53	30053265
	PRJNA390615, PRJNA390988	Blood Exosomes from Pancreatic Adenocarcinoma Patients vs. Normal Control	NCBI SRA	46	30053265
Cancer Cell Line	PRJNA523380	Cancer Cell Line	NCBI SRA	658	31068700
Virus Infection	PRJNA517165	HIV Infection vs. Normal Control	NCBI SRA	22	30185599
	PRJNA517165	HBV Infection vs. Normal Control	NCBI SRA	48	30185599
	PRJNA517165	HCV Infection vs. Normal Control	NCBI SRA	24	30185599
	PRJNA615032	COVID Patients vs. Normal Control	NCBI SRA	4	32416070
Circadian Rhythm	PRJNA454445	Circadian Rhythm	NCBI SRA	153	30201705
Immunotherapy	PRJNA624338	Lymphoma	NCBI SRA	20	33024998
	PRJNA356761	Melanoma	NCBI SRA	58	29033130
	PRJNA557841	Non-Small Cell Lung Cancer	NCBI SRA	27	31537801
	PRJEB25780	Stomach Cancer	EMBL ENA	36	-
Aging	PRJNA413568	Brain	NCBI SRA	18	29507413
	PRJNA690800	Skeletal Muscle	NCBI SRA	53	33795677
	PRJNA223350	Skin	NCBI SRA	20	25977295
Metabolic Diseases	PRJNA642130	Type II Diabetes	NCBI SRA	30	30185599
	PRJNA1021256	Metabolically Healthy / Unhealthy Obesity	NCBI SRA	53	38569471
	PRJNA1071142	Hypertension	NCBI SRA	148	39167456
Neurodegenerative Disease	PRJNA413568	Alzheimer's disease	NCBI SRA	22	29507413
	PRJNA779421	Huntington's disease	NCBI SRA	28	39028640
	PRJNA1166189	Parkinson's disease	NCBI SRA	6	40164620
Reproduction	PRJNA421274	Oocytes	NCBI SRA	147	30472193
Wound Healing	PRJNA730912	Skin	NCBI SRA	20	39366968

2.2 Data structure

2.3 Read mapping, quantification and normalization

All samples are processed by a standardized RNA-seq pipeline (Trimmomatic, FastQC, STAR, RSeQC, Kallisto and featureCounts/ RSEM) to get the abundance matrixes (reads count, CPM, FPKM and TPM) of lncRNAs. The raw abundance matrixes are normalized by TMM method.

2.4 Estimation of transcription reliability

LncExpDB considers lncRNA genes with maximum expression values less than 1.0 TPM in a certain biological condition as not expressed (NE). If the lncRNA genes are tagged with NE in all biological conditions available, they are most likely unreliable lncRNA genes. Of course, it is possible that this definition may change when novel biological conditions are covered.

2.5 Estimation of lncRNA expression capacity

All expressed genes(lncRNAs and mRNAs) are ranked in a specific condition (time point/stage/tissue/cell/component/processing). Specifically, genes with expression values greater than the upper quantile are classified as “H” (high expression level), those less than the lower quantile as “L” (low expression level), and the remaining as “M” (medium expression level). High-capacity lncRNAs (HCL) are genes with “H” classification in at least one condition, and low-capacity lncRNAs (LCL) are those with “L” in all conditions, and the remaining are medium-capacity lncRNAs (MCL). It is noted that with more biological conditions covered, LCL or MCL may change to MCL or HCL.

2.6 Identification of high-confidence featured lncRNAs

LncExpDB identifies and characterizes featured lncRNA genes that are specifically expressed in a certain cell line/tissue, differentially expressed in the context of cancer or virus infection, enriched in a subcellular compartment, dynamically expressed during cell differentiation or embryo/organ development, or periodically expressed with circadian rhythm.

The featured genes are identified using specialized methods with strict criteria:

Time-course expression patterns: R-square >= 0.7 and adjusted p-value < 0.05, maSigPro;

Stage-specific genes and tissue/cell-specific genes: τ (tissue-specific index) >= 0.9, maximum TPM >= 10;

Consistently expressed genes: τ <= 0.35, maximum TPM >= 10;

Differentially expressed genes in virus infection ,exosomes,cancer immunotherapy,human aging and Metabolic Diseases: |log2 foldchange| >= 1 and adjusted p-value <= 0.05, DeSeq2;

Organelle-enriched genes: log2 foldchange >= 1 and adjusted p-value <= 0.05, DeSeq2;

Circadian genes: meta2d and BH < 0.05, MetaCycle.

2.7 LncRNA-mRNA interaction prediction

LncExpDB predicts lncRNA-mRNA interactions based on co-expression networks. Co-expressions relationships between lncRNAs and mRNAs are identified using the Pearson correlation coefficient (adjusted p-value < 0.01 and |r|>=0.5). It is noted due to the extremely small sampling size (n = 4), the dataset of “COVID patients vs. normal control” is not analyzed in this section.

Database Usage

3.1 Quick start in LncExpDB

Enter a gene symbol or gene ID (LncExpDB ID) in the search box on the homepage to explore the lncRNA of interest. In the “Resources” part or “Context” section in the navigation bar, the click of each context will lead you to explore the expression profiles of featured lncRNAs and lncRNA-mRNA interactions across different biological conditions in the corresponding biological contexts, where you can view the defined featured genes or explore a group of lncRNA genes of interest with customized filtration.

To overview expression capacities/featured genes/interactions across different contexts, please click on “Expression Capacity”, “Featured Genes” and “Interactions” in the navigation bar.

3.2 Browse lncRNA genes in LncExpDB

You can browse all lncRNAs in the "Genes" page with the basic information of gene id/symbol, classification, chromosome, strand, location, gene length and transcript number. You can search lncRNAs of interest by gene id/transcript id derived from LncBook v1.2, RefLnc, NONCODE v5, GENCODE v33, CHESS v2.2, FANTOM-CAT (lv4_strigent) and BIGTranscriptome or gene symbol derived from HGNC, chromosome or classification type, and the gene id is linked to detailed information page of expression profiles in different contexts. In the detaied gene page, all corresponding gene and transcript id provide hyperlinks to their orginal pages. In addition, users can view our reference gene track on UCSC Genome Browser.

3.3 Explore featured genes in LncExpDB

You can explore featured lncRNAs in the "Featured Genes" page, which covers tens of thousands of featured genes with specific expression patterns in at least one biological context. You can filter and/or re-order the table content using the categories and search boxes in the header line. Each gene id is linked to detailed information page of expression profiles in different contexts.

3.4 View featured lncRNAs and interactions among biological contexts in LncExpDB

You can view all types of biological samples in the "Contexts" page including normal tissues and cell lines, organ development, preimplantation embryos, cell differentiation, subcellular localization, exosome, cancer cell line, virus infection and circadian rhythm. Each context page contains the tabs of “Featured Genes” and “Interaction”.

By clicking the tab of “Featured Genes”, you can select specific datasets of interest and browse all defined featured genes, e.g., specifically or consistently expressed genes in a certain context. In addition, you can select a specific group of genes with custom thresholds. You can filter and/or re-order the expression profile table using the categories and search boxes in the header line.

By clicking the tab of “Interactions”, you can select specific datasets of interest and browse the cis or trans interactions between lncRNAs and mRNAs. Moreover, you can select a specific group of interaction by custom thresholds or search the related interactions by lncRNA/protein-coding id or symbol.

3.5 Browse expression capacity in LncExpDB

In the "Expression Capacity" page, you can browse the lncRNA’s expression capacity in various biological contexts. You can filter for high-capacity lncRNAs in one or multiple contexts using the categories and in the header line of expression capacity table. Furthermore, the “Chart” enables visualization of expression level distribution among all the biological conditions. Each gene id is linked to detailed information page of expression profiles in different contexts.

3.6 Query lncRNA-mRNA interactions in LncExpDB

You can visualize all lncRNA-mRNA interactions in the “Interactions” page, which includes the detail information of lncRNAs-mRNA pairs, pearson correlation coefficient value, p values and distance. The “search by” tab allows you to narrow down the results according to gene of your interest. Each gene id is linked to detailed information page of expression profiles in different contexts.

3.7 Download data in LncExpDB

The “Downloads” page contains all the files that you can download such as: i) reference gene model for RNA-seq analysis, ii) expression profiles, iii) expression levels, iv) featured genes and v) co-expression matrix in various biological contexts.

3.8 Statistic results in LncExpDB

In the page of “Statistics”, you can find and download all statistical analytics results for i) gene annotation statistics, such as lncRNA integration, exon and transcript number distribution and lncRNA classification, ii) expression statistics, including expression profiles and distribution of featured lncRNAs in different biological contexts, and iii) lncRNA-mRNA interaction distribution.

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