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SPOROS: A pipeline to analyze DISE/6mer seed toxicity.
Elizabeth T Bartom1,2, Masha Kocherginsky2, Bidur Paudel3
1Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.
Plos Computational Biology
|March 31, 2022
Summary
We developed SPOROS, a tool to analyze short (s)RNA sequences for 6mer seed toxicity, a mechanism that can cause cell death. SPOROS predicts toxicity by examining the critical 2-7 positions of sRNAs, regardless of their origin, aiding disease research.
Area of Science:
- Molecular Biology
- Genetics
- Bioinformatics
Background:
- microRNAs (miRNAs) are small noncoding RNAs regulating gene expression via seed sequences.
- Specific G-rich 6mer seed sequences can induce cell death (DISE) by targeting essential genes.
- Standard small (sm)RNA sequencing analysis does not fully capture 6mer seed toxicity mechanisms.
Purpose of the Study:
- To develop a computational pipeline for predicting and comparing 6mer seed toxicity of short (s)RNAs.
- To provide a workflow for analyzing sRNA data independent of miRNA biogenesis.
- To assess 6mer seed toxicity in various biological contexts, including cancer and neurodegenerative diseases.
Main Methods:
- Developed SPOROS, a semi-automated bioinformatics pipeline.
- Focused analysis on the critical 2-7 seed region of sRNAs for RISC loading.
- Applied SPOROS to analyze RISC-bound sRNAs in cancer cell lines and smRNA-Seq data from Alzheimer's patient brains.
Main Results:
- SPOROS successfully predicts and compares 6mer seed toxicity across different samples and sRNA types.
- Demonstrated the pipeline's utility in analyzing cancer cell lines with varying miRNA production.
- Showcased application to publicly available brain smRNA-Seq data, differentiating normal and Alzheimer's samples.
Conclusions:
- SPOROS offers a novel approach to analyze 6mer seed toxicity in diverse smRNA-Seq datasets.
- The pipeline facilitates research into DISE and its role in disease.
- SPOROS is a valuable tool for investigating sRNA function in various normal and pathological conditions.
