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Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
Published on: April 26, 2017
LncAS2Cancer: a comprehensive database for alternative splicing of lncRNAs across human cancers
Yulan Deng1, Hao Luo1, Zhenyu Yang1
1Department of Thoracic Surgery, West China Hospital, Sichuan University.
Abstract:
Accumulating studies demonstrated that the roles of lncRNAs for tumorigenesis were isoform-dependent and their aberrant splicing patterns in cancers contributed to function specificity. However, there is no existing database focusing on cancer-related alternative splicing of lncRNAs. Here, we developed a comprehensive database called LncAS2Cancer, which collected 5335 bulk RNA sequencing and 1826 single-cell RNA sequencing samples, covering over 30 cancer types. By applying six state-of-the-art splicing algorithms, 50 859 alternative splicing events for 8 splicing types were identified and deposited in the database. In addition, the database contained the following information: (i) splicing patterns of lncRNAs under seven different conditions, such as gene interference, which facilitated to infer potential regulators; (ii) annotation information derived from eight sources and manual curation, to understand the functional impact of affected sequences; (iii) survival analysis to explore potential biomarkers; as well as (iv) a suite of tools to browse, search, visualize and download interesting information. LncAS2Cancer could not only confirm the known cancer-associated lncRNA isoforms but also indicate novel ones. Using the data deposited in LncAS2Cancer, we compared gene model and transcript overlap between lncRNAs and protein-coding genes and discusses how these factors, along with sequencing depth, affected the interpretation of splicing signals. Based on recurrent signals and potential confounders, we proposed a reliable score to prioritize splicing events for further elucidation. Together, with the broad collection of lncRNA splicing patterns and annotation, LncAS2Cancer will provide important new insights into the diverse functional roles of lncRNA isoforms in human cancers. LncAS2Cancer is freely available at https://lncrna2as.cd120.com/.
Insights
A new database, LncAS2Cancer, catalogs over 50,000 alternative splicing events in long non-coding RNAs (lncRNAs) across 30 cancer types. This resource aids in understanding lncRNA isoform functions in cancer development and identifies potential biomarkers.
Area of Science:
- Genomics
- Bioinformatics
- Cancer Research
Background:
- Long non-coding RNAs (lncRNAs) play crucial roles in tumorigenesis, with their functions often being isoform-dependent.
- Aberrant alternative splicing patterns in lncRNAs are implicated in cancer-specific functions.
- A dedicated database for cancer-related lncRNA alternative splicing is currently lacking.
Purpose of the Study:
- To develop and present LncAS2Cancer, a comprehensive database for lncRNA alternative splicing events in human cancers.
- To provide a platform for exploring the functional impact, regulatory mechanisms, and biomarker potential of lncRNA isoforms in cancer.
Main Methods:
- Collected and integrated data from 5335 bulk and 1826 single-cell RNA sequencing samples across over 30 cancer types.
- Applied six advanced splicing algorithms to identify 50,859 alternative splicing events across 8 splicing types.
- Incorporated splicing patterns under various conditions, functional annotations, and survival analysis data.
Main Results:
- LncAS2Cancer houses extensive data on lncRNA alternative splicing events, including isoform-specific information and potential regulatory insights.
- The database confirmed known cancer-associated lncRNA isoforms and identified novel ones.
- Analysis facilitated comparisons of gene models, transcript overlaps, and the impact of sequencing depth on splicing interpretation.
Conclusions:
- LncAS2Cancer provides a valuable resource for investigating the diverse roles of lncRNA isoforms in human cancers.
- The database enables the prioritization of splicing events for further research and biomarker discovery.
- It offers new insights into the functional specificity of lncRNA splicing in cancer progression.
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