• AStruct: detection of allele-s...

*Result*: AStruct: detection of allele-specific RNA secondary structure in structuromic probing data.

Title:
AStruct: detection of allele-specific RNA secondary structure in structuromic probing data.
Authors:
Xu Q; State Key Laboratory of Oncology in South China, Cancer Center, Collaborative Innovation Center for Cancer Medicine, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510060, China.; Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, 02215, USA., Bao X; State Key Laboratory of Oncology in South China, Cancer Center, Collaborative Innovation Center for Cancer Medicine, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510060, China., Lin Z; Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China., Tang L; State Key Laboratory of Oncology in South China, Cancer Center, Collaborative Innovation Center for Cancer Medicine, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510060, China., He LN; State Key Laboratory of Oncology in South China, Cancer Center, Collaborative Innovation Center for Cancer Medicine, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510060, China., Ren J; State Key Laboratory of Oncology in South China, Cancer Center, Collaborative Innovation Center for Cancer Medicine, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510060, China., Zuo Z; State Key Laboratory of Oncology in South China, Cancer Center, Collaborative Innovation Center for Cancer Medicine, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510060, China. zuozhx@sysucc.org.cn., Hu K; Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. hukunh@mail.sysu.edu.cn.
Source:
BMC bioinformatics [BMC Bioinformatics] 2024 Mar 01; Vol. 25 (1), pp. 91. Date of Electronic Publication: 2024 Mar 01.
Publication Type:
Journal Article
Language:
English
Journal Info:
Publisher: BioMed Central Country of Publication: England NLM ID: 100965194 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-2105 (Electronic) Linking ISSN: 14712105 NLM ISO Abbreviation: BMC Bioinformatics Subsets: MEDLINE
Imprint Name(s):
Original Publication: [London] : BioMed Central, 2000-
MeSH Terms:
RNA*/genetics , RNA*/chemistry , Gene Expression Regulation*, High-Throughput Nucleotide Sequencing/methods ; Alleles ; RNA Splicing
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Grant Information:
2021B1515020108 the Program for Guangdong Basic and Applied Basic Research Foundation; 2017ZT07S096 Guangdong Introducing Innovative and Entrepreneurial Teams; SL2024A03J00312 the Guangzhou Municipal Institute Enterprise Joint Funding Project
Contributed Indexing:
Keywords: Allele-specific events; Functional variants; RNA secondary structure; Structuromic probing data
Substance Nomenclature:
63231-63-0 (RNA)
Entry Date(s):
Date Created: 20240301 Date Completed: 20240304 Latest Revision: 20240725
Update Code:
20260130
PubMed Central ID:
PMC11264973
DOI:
10.1186/s12859-024-05704-x
PMID:
38429654
Database:
MEDLINE

*Further Information*

*Background: Uncovering functional genetic variants from an allele-specific perspective is of paramount importance in advancing our understanding of gene regulation and genetic diseases. Recently, various allele-specific events, such as allele-specific gene expression, allele-specific methylation, and allele-specific binding, have been explored on a genome-wide scale due to the development of high-throughput sequencing methods. RNA secondary structure, which plays a crucial role in multiple RNA-associated processes like RNA modification, translation and splicing, has emerged as an essential focus of relevant research. However, tools to identify genetic variants associated with allele-specific RNA secondary structures are still lacking.
Results: Here, we develop a computational tool called 'AStruct' that enables us to detect allele-specific RNA secondary structure (ASRS) from RT-stop based structuromic probing data. AStruct shows robust performance in both simulated datasets and public icSHAPE datasets. We reveal that single nucleotide polymorphisms (SNPs) with higher AStruct scores are enriched in coding regions and tend to be functional. These SNPs are highly conservative, have the potential to disrupt sites involved in m6A modification or protein binding, and are frequently associated with disease.
Conclusions: AStruct is a tool dedicated to invoke allele-specific RNA secondary structure events at heterozygous SNPs in RT-stop based structuromic probing data. It utilizes allelic variants, base pairing and RT-stop information under different cell conditions to detect dynamic and functional ASRS. Compared to sequence-based tools, AStruct considers dynamic cell conditions and outperforms in detecting functional variants. AStruct is implemented in JAVA and is freely accessible at: https://github.com/canceromics/AStruct .
(© 2024. The Author(s).)*