Rfam: updates to the RNA families database

Gardner, Paul P.; Daub, Jennifer; Tate, John G.; Nawrocki, Eric P.; Kolbe, Diana L.; Lindgreen, Stinus; Wilkinson, Adam C.; Finn, Robert D.; Griffiths-Jones, Sam; Eddy, Sean R.; Bateman, Alex

New graphical representations of secondary structures have been added to the Rfam website, based on software from the Vienna RNA package (8) . We now annotate several statistics directly on secondary structure diagrams, including sequence conservation, covariation, base-pair conservation and the maximum CM scores (Figure 2 ). The sequence conservation metric uses a metric computed for each column in the alignment; this is the frequency of the most common nucleotide in each column (Figure 2A ). The covariation metric is based upon that used by RNAalifold (9) . For each base pair in the consensus structure and for each pair of sequences in the alignment, the difference in structurally consistent and inconsistent mutations is taken. Each mutation is weighted using a treeweighting scheme (10) and this value is then normalized by the number of possible mutations ( Figure 2B ). The base-pair conservation metric is the fraction of canonical base pairs (Watson-Crick and G:U) in any two columns that correspond to a base pair in the consensus structure ( Figure 2C) . The maximum covariance model score and corresponding nucleotide/base pair is computed for each node in the CM. The resulting sequence, structure and bitscores are used to produce a marked up secondary structure ( Figure 2D ).