TIE

TIE annotates and aggregates microRNA isoforms (isomiRs) from over 11,000 adult and pediatric tumor samples from The Cancer Genome Atlas (TCGA) and the Therapeutically Applicable Research to Generate Effective Treatment (TARGET) datasets to enable analysis of templated and non-templated nucleotide variants in cancer.

Key Features:

• Dataset coverage: Contains isomiR data derived from more than 11,000 tumor samples spanning adult and pediatric cohorts from TCGA and TARGET.
• IsomiR abundance reporting: Quantifies isomiR representation, which comprises approximately 40%–60% of total miRNA counts in these samples.
• Templated and non‑templated nucleotide annotation: Annotates both templated and non‑templated nucleotide additions in isomiR sequences.
• Heterogeneous sequence annotation: Annotates heterogeneous isomiR sequences to capture sequence variants and isoforms.
• Aggregation across samples and datasets: Aggregates variant data across all samples and datasets to increase detection of recurrent and low‑frequency events.
• Addressing mapping challenges: Mitigates issues posed by short read length and high isomiR heterogeneity through targeted annotation and aggregation strategies.
• Illustrative analyses: Includes example analyses of specific miRNAs such as miR-21 and miR-30a to demonstrate isomiR-level insights.

Scientific Applications:

• miRNA regulation in cancer: Enables investigation of isomiR repertoires and their roles in cancer-associated gene regulation across tumor types.
• Seed and pairing alteration analysis: Facilitates identification of isomiRs that modify seed sequences or enhance 3' pairing stability, with potential effects on target specificity.
• miRNA turnover and decay detection: Supports detection of isomiR species that may represent decay intermediates indicative of miRNA turnover.
• Comparative tumor analyses: Allows comparative analyses between adult and pediatric tumors using TCGA and TARGET cohorts.
• Discovery of regulatory mechanisms and targets: Aids discovery of novel regulatory mechanisms and candidate therapeutic targets mediated by isomiRs.

Methodology:

Annotates heterogeneous isomiR sequences and both templated and non‑templated nucleotides, and aggregates variant data across TCGA and TARGET tumor samples (over 11,000 samples).