SPOROS

SPOROS analyzes 6mer seed toxicity in small RNA sequencing (smRNA-Seq) data to identify and predict G-rich 6mer seeds in microRNAs (miRNAs) and other short RNAs that can induce cell death (Death Induced by Survival gene Elimination, DISE) by targeting complementary C-rich 6mer matches in essential genes via RISC-mediated seed targeting.

Key Features:

• 6mer seed extraction: Extracts and analyzes 6mer seed sequences from smRNA-Seq reads focusing on seed positions 2–7.
• miRNA and RISC context: Considers microRNAs (miRNAs, 18–22 nucleotides) and other short RNAs capable of entering the RNA-induced silencing complex (RISC), including guide-strand seed positions 2–7/8.
• DISE identification: Identifies G-rich 6mer seeds predicted to induce Death Induced by Survival gene Elimination (DISE) by targeting complementary C-rich seed matches in essential genes.
• Alignment-independent approach: Operates without requiring genomic alignment of smRNA-Seq reads, using a seed-centric analysis rather than full read-to-genome mapping for miRNA quantification.
• Semi-automated workflow: Implements a semi-automated workflow tailored to assess toxicity based on the exact seed position 2–7 of short RNAs.
• Comparative outputs: Produces outputs that enable prediction and comparison of 6mer seed toxicity across different cellular samples.

Scientific Applications:

• Cancer cell line analysis: Analysis of RISC-bound small RNAs in cancer cell lines, including comparisons between wild-type cells and mutant lines deficient in miRNA production.
• Neurodegenerative disease studies: Examination of smRNA-Seq data from postmortem brains to compare 6mer seed toxicity patterns between normal individuals and those with Alzheimer’s disease.
• Comparative toxicology across conditions: Assessment of 6mer seed toxicity across normal and pathological conditions to investigate miRNA-mediated impacts on cell survival.

Methodology:

Extracts seed sequences at positions 2–7 from smRNA-Seq reads without genome alignment and computes predictions and comparative metrics of 6mer seed toxicity across samples.