Tumor IsomiR Encyclopedia (TIE): a pan-cancer database of miRNA isoforms

MicroRNAs (miRNAs) function as master regulators of gene expression in many physiological and pathological conditions including cancer. Sequence variants or isoforms (isomiRs) can account for between 40 to 60% of total miRNA counts, yet despite this overwhelming abundance, their function continues to be debated. Recent studies demonstrate that certain isomiRs can regulate unique sets of target mRNAs by altering their seed sequence or stabilizing 3 pairing, while others are decay intermediates indicating an active miRNA turnover. Given their short sequence length and high heterogeneity, mapping isomiRs can be challenging; without adequate depth and data aggregation, low frequency events are often disregarded. To address these challenges, we present the Tumor IsomiR Encyclopedia (TIE): a dynamic database of isomiRs from over 10,000 adult and pediatric tumor samples in The Cancer Genome Atlas (TCGA) and The Therapeutically Applicable Research to Generate Effective Treatments (TARGET) projects. A key novelty of TIE is its ability to annotate heterogeneous isomiR sequences and aggregate the variants obtained across all samples and datasets. The database provides annotation of templated and non-templated nucleotides as well as other advanced analysis. All data can be browsed online or downloaded as simple spreadsheets. Here we show analysis of isomiRs of miR-21 and miR-30a to demonstrate the utility of TIE. TIE search engine and data are hosted at https://isomir.ccr.cancer.gov/.