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The process of attaching contextual information to a biomolecular (DNA, RNA, or protein) sequence, such as the location of genes, promoters, or repeats in genomic DNA, or the function of a protein.

Annotations may include the location of particular features (a gene on a segment of chromosomal DNA, or a conserved domain on a protein sequence), the function of the sequence or one of its features, or other descriptive contextual information.

The most common sequence annotations describe the location and function of protein-coding genes, tRNA genes, and rRNA genes on a genomic sequence. Tools such as Prokka and Maker were designed for this kind of genome annotation in prokaryotes and eukaryotes. Other features that may be annotated include the location of transposable and other repetitive elements, binding sites and other regulatory sequences, restriction sites, and many other features.

Attaching functional information to an entire sequence or to one of its annotated features often involves adopting a functional description from a highly similar sequence whose function has been determined previously by experiment. Due to the rapid growth of sequence data in public databases, however, most functional annotation is several degrees removed from any sequence with direct experimental confirmation.